2024 ASCO GI 摘要集

其他综合与多学科· 未分类与其他 · 2024

Predicting recurrence using a tumor-uninformed ctDNA assay detecting MRD in patients with resected stage II or III colorectal cancer: Subset analysis from the GALAXY study in CIRCULATE-Japan. First Author: Yoshiaki

Predicting recurrence using a tumor-uninformed ctDNA assay detecting MRD in patients with resected stage II or III colorectal cancer: Subset analysis from the GALAXY study in CIRCULATE-Japan. First Author: Yoshiaki

Authors

Keywords

U10CA180868, -180822, UG1CA189867, Guardant Health. Clinical trial information: NCT04068103. Research Sponsor: NIH, GuardantHealth

Abstract

The American Society of Clinical Oncology assumes no responsibility for errors or omissions in this publication. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosage, the method and duration or administration, or contraindications. It is the responsibility of the treating physician or other health care professional, relying on independent experience and knowledge of the patient, to determine drug, disease, and the best treatment for the patient.

7

Oral Abstract Session

Organ-preservation in rectal cancer: What is at risk when offering watch and wait for a clinical complete response? Data from 2 international registries in rectal cancer. First Author: Laura Melina Fernandez, Champalimaud Foundation, Lisbon, Portugal Background: Organ-preservation has become an attractive alternative to total mesorectal excision (TME) among patients with rectal cancer following neoadjuvant therapy. Patients who achieve a clinical complete response (cCR) are currently offered watch-and-wait (WW) without immediate resection. Nearly 30% of these patients will develop local regrowth usually within 3 years from initial decision to WW. While salvage resection is frequently feasible, keeping the primary tumor in situ (despite clinically undetectable) may contribute to the risk for development of subsequent distant metastases (DM). The aim of the present study is to compare the risk of DM between patients with local regrowth (LR) after WW (undetectable residual disease) and patients with near-complete pathological response managed by TME at time of reassessment of response. Methods: Data from patients with rectal cancer following neoadjuvant therapy entered a prospective international database (IWWD) with cCR managed by WW and subsequent LR were compared to patients managed by TME from a prospectively maintained national registry (VIKINGO project). Nearcomplete response was defined at the presence of #10% residual cancer cells in the resected specimen. Primary endpoint was DM-free survival at 3 years from decision to WW or TME. Cox-logistic regression was performed to search for predictors of DM development. Kaplan-Meier curves were used to compare DM-free survival between groups based on statistically significant features found at multivariate analysis (p#0.05) using log-rank test. Results: 508 patients with LR were compared to 893 patients with near-complete response after TME. Overall, DM rate was significantly higher among local regrowths (22.8% vs. 10.2%,; p#0.001). Independent risk factors for DM included LR (versus TME at reassessment; p=0.001), ypT3-4 status (p=0.016) and ypN+ status (p=0.001) at the time of surgery. 3yr-DM-free survival was significantly worse for patients with local regrowth (75% vs. 87%; p=0.001). When stratified for pathological stage, patients with local regrowth did significantly worse through all stages ypT1-2N0 (p,0.001); ypT3-4N0 (p=0.009) and ypTanyN+ (p,0.001). Conclusions: Development of LR following WW is a significant and independent risk factor for subsequent DM. Final pathological stage is also a risk factor for subsequent DM. Patients with local regrowth have a higher risk for subsequent DM development than patients managed by TME at restaging irrespective of final ypT and ypN status. Leaving the primary undetectable tumor in situ until development of local regrowth may result in worse oncological outcomes. Future studies incorporating organpreservation strategies should focus on the subsequent risk of DM among patients who eventually develop local regrowth as one of clinically relevant primary endpoints.

Research Sponsor: None.

10 Rapid Oral Abstract Session

Health-related quality of life (HRQoL) in patients with metastatic colorectal cancer (mCRC) treated with sotorasib and panitumumab (pmab) versus trifluridine/tipiracil (T/T) or regorafenib (rego) in CodeBreaK 300. First Author: Dominik Paul Modest, Department of Hematology, Oncology and Cancer Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany

Background: CodeBreaK 300 (NCT05198934) is a phase 3, multicenter, randomized, open-label study, evaluating sotorasib 960 mg (soto960) + pmab, sotorasib 240 mg (soto240) + pmab against investigator's choice T/T or rego in patients with chemorefractory KRAS G12C-mutated mCRC.

The study met its primary endpoint and demonstrated statistically significant improvement in progression-free survival with both doses of sotorasib. This analysis evaluated patient-reported outcomes (PROs) as secondary and exploratory endpoints in CodeBreaK 300. Methods: Change in PRO scores from study baseline through week 8 was compared for soto960+pmab and soto240+pmab vs the control group using a mixed effect model for repeated measures. PRO instruments included the Brief Fatigue Inventory, the Brief Pain Inventory, and the European Organisation for Research and Treatment of Cancer Core 30-item Quality of Life questionnaire. Time to deterioration (TTD) were assessed using Kaplan-Meier plots and Cox proportional hazard models. All analyses were conducted on patients with baseline and at least one post-baseline PRO score. Results: 160 pts were randomized 1:1:1 to soto960+pmab (n=53), soto240+pmab (n=53), or T/T or rego (n=54). Compliance rates for PRO assessments were high (.83%) and similar across the three treatment groups. Least square (LS) mean changes from baseline in fatigue at its worst, pain at its worst, physical functioning (PF), and global health status (GHS)/QoL favored the two sotorasib dose groups (Table ). The 95% confidence intervals (CI) suggested improvement in pain at its worst and PF for both sotorasib dose groups, and improvement in GHS/QoL for the soto960+pmab group versus the control group. TTD hazard ratios , 1 indicated a trend in delayed deterioration for patients treated in both sotorasib dose groups. The 95% CIsuggested delays with respect to fatigue at its worst and PF for the soto240+pmab group. Conclusions: In CodeBreaK 300, both doses of sotorasib resulted in better HRQoL and a trend to decreased risk of deterioration vs the control group. In addition to improved clinical outcomes, these findings provide further evidence on the benefit of soto+pmab in patients with chemorefractory mCRC. Clinical trial information: NCT05198934. Research Sponsor: Amgen.

11 Rapid Oral Abstract Session

Peritoneal lavage cytology in patients with curative resection for stage II and III colorectal cancer: A multi-institutional prospective study. First Author: Hirotoshi Kobayashi, Teikyo University Hospital Mizonokuchi, Kawasaki, Japan Background: Although various prognostic factors in patients with colorectal cancer has been reported, the usefulness of intraoperative lavage cytology in patients with colorectal cancer is controversial. The aim of this study was to clarify the usefulness of intraoperative lavage cytology in patients with curative resection for pSage II-III colorectal cancer in a prospective multicenter study. Methods: The 20 member hospitals of the Japanese Society for the Cancer of the Colon and Rectum prospectively registered the patients diagnosed as stage II or III colorectal cancer preoperatively between 2013 and 2017. Among these patients, pStage II-III patients went through analysis. Lavage cytology was performed twice during surgery. The first procedure was performed right after laparotomy, and the second was performed right after specimen retrieval. The primary endpoint of this study was an effect of lavage cytology on 5-year relapse-free survival (RFS) in patients with pStage II-III colorectal cancer. The secondary endpoint was an effect of lavage cytology on 5-year overall survival (OS) and peritoneal recurrence in patients with pStage II-III colorectal cancer. Results: A total of 1378 patients were eligible and went through analysis. The number of patients with pStage II and III colorectal cancer were 670 and 708, respectively. Among 1378 patients, 54 (3.9%) had positive cytology. The median follow-up period of the entire cohort was 5.3 years. In pStage II patients, the 5-year RFS rate with positive and negative cytology was 61.1% and 81.6%, respectively (P = 0.023). The 5-year OS rate of pStage II patients with positive and negative cytology was 67.1% and 91.7%, respectively (P = 0.0083). However, there was no difference in RFS and OS between patients with positive and negative cytology in pStage III patients. Thirty-three patients had peritoneal recurrence. The peritoneal recurrence rate was 11.8% and 1.5% in pStage II patients with positive and negative lavage cytology, respectively (P = 0.032). That was 10.5% and 2.5% in pStage III patients with positive and negative lavage cytology, respectively (P = 0.022). In total, 11.1% of patients with positive lavage cytology had peritoneal recurrence in this cohort.

Conclusions:

The pStage II colorectal cancer patients with negative cytology had better RFS and OS compared to those with positive cytology. Peritoneal lavage cytology was useful in predicting peritoneal recurrence after curative resection for pStage II-III colorectal cancer. Clinical trial information: UMIN000026070. Research Sponsor: The Japanese Society for Cancer of the Colon and Rectum.

15 Poster Session

Validation of a novel web-based application for hepatic arterial infusion floxuridine dosing. First Author: Carleton Scott Ellis, Department of Pharmacy, University of Kentucky HealthCare, Lexington, KY Background: Hepatic arterial infusion (HAI) floxuridine (FUDR) dosing is a complex, multifactorial process with weight-based dosing dependent on the fold change of aspartate aminotransferase, alkaline phosphatase, and total bilirubin relative to reference values from preceding cycles and compounded over time. Given the complexity of dosing calculations and lack of experience with this treatment in community centers, HAI is typically administered only at tertiary oncology centers with limited access for rural disadvantaged patients. We developed an online tool to automate the dosing of FUDR to broaden safe and effective administration of HAI. Methods: The FUDR dosing algorithm developed at Memorial Sloan Kettering Cancer Center was digitalized as eDoseHAI, a novel multi-layer architecture web application tool featuring JavaScript (front-end), C# RESTful API (back-end) and Azure SQL server (data storage with Splunk data lake event registration). To validate this tool, manual dosing from patients who received $1 dose of HAI FUDR at our institution 6/2020-8/2023 was retrospectively compared to app-based dosing. Mismatch between app-based dosing and historical manual dosing was designated as dosing errors, excluding intentional adjustments based on physician discretion. Results: Internal validity was tested by entering records into eDoseHAI from 54 patients who received a total of 370 FUDR cycles (median 6; range 1-19). Ten patients (18.5%) were found to have unintentional dosing errors (e.g., delayed dose reductions) during treatment, impacting 52 cycles (14.1%). The median cycle at first error was 3 (range 2-6), impacting a median of 5 cycles (range 3-12). Dosing errors occurred in only 11.1% of the 45 patients supervised by a senior HAI physician, compared to 55.6% of the 9 patients supervised by three less experienced HAI physicians. Dosing accuracy improved over time; among the 14 patients on active HAI therapy, only 1 had an identified dosing error. eDoseHAI was able to reliably and accurately calculate dosing for all patients. Conclusions: HAI FUDR dosing is nuanced and complex, such that dosing errors occurred even with senior HAI oncologists. eDoseHAI is a web-based application tool designed to improve accuracy and thus safety of HAI dosing. We plan to further validate eDoseHAI using external data from an international HAI consortium, and to conduct a phase II clinical trial in which our team supervises FUDR dosing by community oncologists using eDoseHAI's supervisory mode with a goal to disseminate HAI therapy to disadvantaged rural patients who lack access. Research Sponsor: None.

16 Poster Session

Rectal cancer disparities in a large, diverse health system in New York. First Author: Phyu Thin Naing, Northwell Health, New Hyde Park, NY Background: The disproportionate burden of colorectal cancer among African American (AA) patients is striking, with 40% increase relative risk of death compared to non-AA White population (Seer Cancer Statistics Review, 2022) . NAPRC aims to ensure equitable delivery of evidence-based treatment to ensure optimal outcomes for all patients. Our study investigated whether care delivery outcomes differed for AA patients in our NAPRC cohort of patients, and explored the reasons associated with the disparities. Methods: Rectal cancer patients were identified by pooling 2019 to 2022 data from NAPRC coordinators from 4 regional sites under Northwell Health, spread across a large geographical area in NY: Westchester and Phelps (Northern), Lenox Hill (Western), NSUH/LIJ (Central), and Huntington (Eastern). The primary outcome was time from biopsy (Bx) to treatment (Tx) initiation, where Tx was rectal cancer resection, chemotherapy, or radiotherapy. The secondary outcome was time from tumor board (TB) to first Tx. Social deprivation index (SDI) is a composite measure of 7 demographic characteristics collected in the American Community Survey (ACS) matched with zip codes of patients. SDI and the deprivation severity have a positive and linear correlation.

Results: We collected data on 381 patients; 337 had documented race data: 42 AA and 295 non-AA (includes White, Asians and others). AA, compared to non-AA, patients had significantly longer median time from Bx to Tx in Western (66 vs 42 days, p,0.01) and Central (56 vs 41 days, p= 0.03) regions. AA patients also had higher time from TB to Tx in the Western (29 vs 17 days, p=0.01) and Central (26 vs 19 days, p= 0.05) regions, respectively. Longer time to treatment was associated with: AA patients, Medicare patients, and patients requiring social work assistance. SDI is positively correlated with time from Bx to Tx (p,0.01) and time from TB to Tx (p,0.01). Conclusions: There are significant disparities between AA vs Non-AA in both primary and secondary outcomes. These findings highlight the need for further exploration such as interviewing social workers and developing patient surveys to explore why the care disparities in AA population is more significant in certain regions than others. We need to account for race and social barriers in treating cancer patients. Taking a proactive approach by sending social work referrals for all AA patients may be a potential solution for these marginalized patients. Research Sponsor: None.

4s COLORECTAL CANCER

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Poster Session

Colon cancer screening disparities among limited English proficient patients during implementation of patient navigation services. First Author: Rebecca Yao, Mayo Clinic, Rochester, MN Background: Age-appropriate colon cancer screening has long demonstrated effectiveness in reducing colon cancer incidence and mortality. However, despite a gradual rise in compliance with colon cancer screening, significant disparities remain, particularly among patients with limited English proficiency (LEP). Multitarget stool DNA (MT-sDNA) testing (Exact Sciences, Madison, WI) has been available over the past decade in the United States as a lower-cost and non-invasive option for screening. In 2019, Exact Sciences began to offer patient navigation services comprising outbound phone, text, and e-mail reminders, and inbound phone support (.200 languages) with all MT-sDNA orders. In this study, we aimed to evaluate the disparity in successful MT-sDNA testing between LEP and EP patients in a time frame when patient navigation services were active.

Methods: We performed a retrospective cohort study of patients 45-75 years old enrolled in the primary care setting of our institution who received an order for MT-sDNA screening during a period in which patient navigation services began to be offered. A multi-state Cox model was constructed with time to MT-sDNA or other CRC screening predicted by English proficiency accounting for age and gender. Wald tests were used to test the association of CRC screening completion and English proficiency. Rates of completion of MT-sDNA screening and other CRC screening following MT-sDNA test ordering were calculated using the Kaplan-Meier method. Results: Of the 5016 patients evaluated and referred for multitarget stool DNA testing from May 1 st , 2021, and May 1 st , 2022, 154 patients were of LEP, and 4862 were English proficient (EP). At 180 days following a MT-sDNA test order the rate of completion for the LEP patients was 50.2% (95% CI: 42.8-58.7%) versus 70.3% (95% 69.1-71.6%) for EP individuals (p=0.001). A small portion of individuals also completed another type of CRC screen, 3.3% for LEP and 2.5% for EP (p=0.99) . Conclusions: This study is consistent with the existing research demonstrating LEP as a significant demographic group linked with decreased participation in cancer screening. Our findings indicated that despite the availability of patient navigation services, individuals with LEP were still less likely to complete an MT-sDNA test successfully when compared to those with EP. Research Sponsor: None.

18 Poster Session

Survival by race and ethnicity among insured patients with early-onset colorectal cancer. First Author: Jeffrey Lee, Kaiser Permanente, San Francisco, CA Background: Colorectal cancer (CRC) incidence and mortality have decreased in the United States over the past 3 decades, but the incidence is increasing in those ,50 years of age (i.e., early-onset CRC). Studies have examined racial and ethnic differences in CRC incidence in this age group, but little is known about differences in survival. Examining survival by race and ethnicity among patients with early-onset CRC may provide insights about differences in risk factors, access to care, and treatment. Methods: This retrospective cohort study included Kaiser Permanente Northern California health plan members 18-49 years of age and diagnosed with CRC between 2006-2019. Race and ethnicity were self-reported as Asian/Pacific Islander, Black, Hispanic, or White. 5-year survival probability was assessed using Kaplan-Meier analyses. Cox regression with adjustment was used to evaluate associations between race and ethnicity and 5year survival. Results: Of 1620 patients, median age was 45.4 years, 47% were female, 20% were Asian/Pacific Islander, 8% Black, 22% Hispanic, and 50% non-Hispanic White persons. Adjusted for age, sex, and comorbidities, Hispanic persons had a higher risk of death at 5 years compared to White persons (hazard ratio [HR] : 1.41; 95% confidence interval [CI]: 1.09-1.83) (Table ). Sequentially adding annual household income and neighborhood deprivation index had no impact on the association; adding tumor stage decreased the HR to 1.14 (0.87-1.49) and adding tumor and treatment factors decreased the HR to 1.08 (0.82-1.42). Risk of death among Asian/Pacific Islander and Black patients did not differ from White patients. Conclusions: Among insured patients with early-onset CRC, Hispanic patients had a higher risk of death at 5 years than patients of White race.

19 Poster Session

Prevalence and predictors of aspirin/NSAID use among patients with Lynch syndrome (LS). First Author: Sachi Singhal, Fox Chase Cancer Center, Philadelphia, PA Background: LS is among the most common hereditary cancer (CA) syndromes, underlying 3% cases of colorectal CA (CRC) and 8% CRC ,50 yrs. LS patients have a high lifetime risk of CRC which is lowered by intensive colonoscopy surveillance. However, interval CRC can still develop, and adjunctive therapies like ASA and NSAIDs have been recognized for their CP benefits, with 35% risk reduction associated with sustained (.2 yrs) ASA use. Existing data are scarce on uptake of CP in LS pts, as well as patient-level factors that may impact uptake. Methods: PREVENTLynch recruited LS participants in the FoxChase Cancer Center (FCCC) Risk Registry, who were invited to complete a one-time e-survey after providing informed consent (1/2020 -6/2020; IRB 20-8014) . This survey was additionally provided online (PREVENTLynch-II) to US and international patients through 2 patient advocacy websites (10/2022-7/ 2023). Demographic/personal/familial CA history were collected. Perceived inconvenience, side effects, reassurance, and likelihood of recommending available and emerging CA prevention modalities were measured on 9-point scales (low=1; high=9). Results: 296 patients with LS completed the survey. Median age was 53 yrs , and overall CP use was 37.5%. No significant variation in CP uptake was seen based on race, age, marital status or geographic region (nationally and internationally). Personal history of cancer was reported by 56.4%, but was not associated with CP (p=0.6). Gene mutated (MLH1, MSH2, MSH6, PMS2) was not associated with CP (p=0.5).CP users vs non-users perceived greater convenience (mean 1.32 vs 1.90 respectively, p=0.02), lower concern for side effects (2.30 vs 3.61, p=0.0008), and higher perceived preventive reassurance from CP use (5.68 vs 3.93 p,0.0001). CP users were more likely to recommend CP to others (7.57 vs 4.49, p,0.0001). Conclusions: CP uptake is low among patients with LS. Patient perceptions of CP convenience, side effects and preventive benefits predicted CP uptake whereas factors such as age, sex, geographical location, gene affected and personal history of malignancy did not. This suggests a critical need for education addressing negative perceptions of CP among LS patients to improve CP uptake. Research Sponsor: None.

20 Poster Session

Understanding causes of racial/ethnic survival disparity in 47,178 patients with colorectal cancer: A quantitative evaluation of molecular, socioeconomic, and clinical covariates. First Author: Mahmoud M.G. Yousef, The University of Texas MD Anderson Cancer Center, Houston, TX Background: A disparity in overall survival (OS) of colorectal cancer (CRC) patients based on self-reported race has been observed. Separately, differing frequencies of driver gene mutations among racial groups have been observed. The contribution of these molecular differences to disparity in outcomes is not well understood. We conducted a systematic investigation of molecular, socioeconomic (SES) and clinical covariates to quantitate the degree to which each influences the OS disparity. Methods: The Foundry software platform was used to query electronic health records to identify CRC patients and extract clinical and molecular data. The relative contribution of each variable to OS disparity was determined using mediation analysis consisting of sequential multivariate Cox regression models. Results: 47,178 patients with CRC diagnosed between 1973 and 2023 with selfreported race were identified. Relative to Non-Hispanic white (NHW), African American (AA) had worse OS (HR=1.16, P= 1.5E-6), while Asians and Hispanics had better OS (HR=0.66, P=4.2E-13 and HR=0.86, P=3.4E-6, respectively). The magnitude of disparity between AA and NHW was greater in metastatic disease (HR 1.2, P=1.7E-4). Among 7,628 patients with clinical molecular testing, five genes differed significantly in mutation frequencies; APC (54% NHW, 62% AA, 57% Hispanics, 46% Asian, FDR= 0.01), KRAS (45%, 58%, 50%, 44%, FDR=8.4E-9), PIK3CA (17%, 23%, 17%, 12%, FDR=0.006) were higher in AA, while BRAF (8%, 3%, 4%, 7%, FDR=2.4E-8), KIT (4%, 1%, 2%, 3%, FDR=0.013) were higher in NHW. In multivariate analysis mutations of BRAF (HR= 1.9, P=1.2E-8), KRAS (HR= 1.39, P=1.7E-7), and APC (HR= 0.81, P= 5E-4) were significantly associated with OS as was national area deprivation index (HR= 1.07, P=0.004), marital status (HR= 1.16, P=0.03), performance status (HR= 1.42, P= 5.3E-29), disease stage (HR= 1.502, P=4.4E-26), right sided tumors (HR= 1.23, P=0.003), tumor differentiation (HR= 1.22, P=0.004) and MSI-high (HR= 0.37, P=1.8E-7). Mediation analysis identified neighborhood SES as the greatest contributor to disparity (38%), followed by primary tumor side (10%), and molecular characteristics (MSI-status, KRAS and BRAF mutations, 10%). After including all covariates, 39% of disparity remained unaccounted. Conclusions: Systematic evaluation of a large cohort from a single institution confirmed substantial racial disparity in survival and frequencies of driver mutations. SES factors have the largest contribution but account only for forty percent of the disparity, with tumor molecular features also contributing. Molecular characteristics should be incorporated in multicentric studies of racial survival disparity. Future clinical studies should ideally account for genetic ancestry and molecular features when evaluating chemotherapy outcomes. Research Sponsor: National Cancer Institute; the Cancer Prevention & Research Institute of Texas; ASCO.

COLORECTAL CANCER 5s

Disparities and trends in biomarker testing in metastatic colorectal cancer.

First Author: Hannah Ruth Robinson, University of Colorado Cancer Center, Aurora, CO Background: Several therapies with biomarker-based indications have received approvals for use in metastatic colorectal cancer (mCRC) in the past decade. Consequently, biomarker testing is integral for treatment decisions, and guidelines recommend universal RAS, BRAF, and microsatellite instability (MSI)/ mismatch repair protein (MMR) testing in patients with mCRC. This study describes the frequency of biomarker testing in mCRC and explores variables influencing testing patterns. Methods: This study used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database, which contains patient-level data originating from approximately 280 cancer clinics in the United States (~800 sites of care).Adult patients diagnosed with mCRC after January 1, 2013 who received at least 1 line of treatment were included. The percentage of patients who received KRAS, NRAS, BRAF, and MSI/MMR testing as reported in the database was determined. Univariate and multivariable analyses were performed to evaluate factors associated with completion of biomarker testing.

Results: A total of 25,937 patients were included in this analysis. Among these, 81.6%, 60.5%, 63.7%, and 73.4% had documented test results for KRAS, NRAS, BRAF, and MSI/ MMR, respectively, and 51.6% received completed testing for all 4 biomarkers. In a multivariable analysis including 13,894 patients with complete data available for assessed variables, younger age at diagnosis, non-Hispanic or Latino ethnicity, white versus black race, more recent year of diagnosis, community versus academic practice setting, higher socioeconomic status index, and lower Eastern Cooperative Oncology Group performance status (ECOG PS) were associated with increased completion of biomarker testing. Year of diagnosis and ECOG PS had the largest impact. Frequency of testing completion was 73.7% in those diagnosed in or after 2020 compared to 21.5% in those diagnosed from 2013-2015 (odds ratio [OR] 8.56, p,0.001). Complete testing was performed in 59.3% of those with an ECOS PS of 0, compared to 55.1% (OR 0.86, p,0.001), 45.7% (OR 0.62, p,0.001), 38.0% (OR 0.43, p,0.001), and 16.7% (OR 0.16, p=0.019) of those with an ECOG PS of 1, 2, 3, and 4, respectively. Notably, testing was completed in 47.2% versus 50.5% of patients with Hispanic or Latino ethnicity versus non-Hispanic or Latino ethnicity (OR 0.69; p,0.001), and in 48.8% versus 51.6% of black versus white patients (OR 0.82, p=0.001). Conclusions: Based on results from the Flatiron Health database, rates of guideline-recommended biomarker testing in mCRC remain suboptimal and are impacted by age, ethnicity, race, socioeconomic status, practice setting, ECOG PS, and year of diagnosis. These results highlight important disparities in testing that require attention. Encouragingly, rates of testing have significantly increased over the past decade as new biomarker-directed therapies have become available. Research Sponsor: None.

30 Poster Session

Total neoadjuvant therapy using short course radiation with or without SIB to lateral pelvic lymph nodes in locally advanced ugly rectal cancer. First Author: RAHUL KRISHNATRY, Tata Memorial Centre, Mumbai, India Background: Optimal management for lateral pelvic lymph nodes (LPLN) in Ugly locally advanced rectal cancer (LARC) is unknown & is associated with worse outcomes. We hypothesise that total neo-adjuvant (TNT) using Short-course radiotherapy (SCRT) with SIB to lateral pelvic lymph nodes would improve outcomes. Methods: All consecutive patients of LARC with LPLN treated with SCRT-based TNT from Jan 2021 -Dec 2022 were reviewed (IEC No: 4116) . The LPLN (external, internal, common iliac or obturator) was considered radiologically significant based on joint clinic review with classical criteria. They were divided into two groups (SIB-IMRT: up to 30Gy/5#; or not). The chemotherapy schedule was similar to RAPIDO study, followed by TME +/-LPLN dissection based on radiological response assessed in joint clinic. Two groups were compared for baseline features using Fisher's exact/Chi-Square tests as appropriate. Outcomes were reviewed for overall response in LPLN (radiological or pathological), disease outcomes & toxicity (acute radiotherapy CTCAE v5, 30-day Clavien Dindo post-surgical, & HRQL EOTRC QLQ-C30). Results: From 398 patients, 83 (20.8%) were identified with LPLN receiving SCRT with TNT, of which 44 (53.01%) received a SIB boost. Overall, 40% were aged # 45 years, 50% had poor histology (signet, PDAC, Mucinous), 35% had EMVI, and 83% were N2+. The two groups had a similar distribution of baseline features (p.0.05) & were matched for poor prognostic factors. The patients who received a boost were 20% more likely to complete TNT and undergo TME than patients who did not (81.8% vs 61.5%; p=0.0099), mainly due to a significantly lesser event of disease progression before surgery, rendering them inoperable (25% vs 33.3%; p=0.024). Boost was associated with an increased overall response at LPLN by 20% (84.1% vs 64.1%; p=0.011) & decreased need for PLND by 15% in patients considered for surgery (15.9% vs 30.56%; p=0.072). At a median follow-up of 18 months, 26 patients (31.33%) identified with disease progression were similarly distributed in two groups with similar patterns (all but one had distant metastasis, of which 6 had loco-regional failures). A total of 17 deaths with a non-significant trend of higher 18-month OS observed (boost: 83.4+6.3 vs 75.6+7.8%; HR:2.29(CI:0.85 -6.19; p=0.09). None of the patients had acute . grade 3 CTCAE v5 toxicity within 4 weeks of radiotherapy completion. Four (4.8%) deaths were chemotherapy-related, & one postsurgery toxicity with similar . grade 3 Clavien Dindo complications in two arms. EORTC QLQ C-30 PROM scores were similar in two groups. Conclusions: In ugly, poor biology LARC, TNT with SCRT-SIB to LPLN seem safe & feasible with improved response, treatment completion & operability without significantly increase in toxicity rates. Longterm prospective studies are warranted to identify significant survival impact. Research Sponsor: None.

31 Poster Session

Symptom burden in patients with early-onset colorectal cancer: A subgroup analysis of the enhanced, EHR-facilitated cancer symptom control (E2C2) trial. First Author: Michael H. Storandt, Mayo Clinic, Rochester, MN Background: Incidence of early-onset colorectal cancer (eoCRC, ,50 years of age at diagnosis) is increasing globally. However, little is known regarding symptom burden in this sub-population. We compared symptoms in patients with eoCRC to those of patients with average-onset CRC (aoCRC, diagnosed at age $ 50). Methods: E2C2 is a steppedwedge, cluster-randomized pragmatic trial evaluating a collaborative care model for the assessment and management of six symptoms [Sleep disturbance, Pain, Physical function impairment, Anxiety, emotional Distress, and Energy deficit (SPPADE)]. Patients were asked to complete assessments rating each of these symptoms on an 11-point numerical rating scale. Symptom severity was classified as mild (0-3), moderate (4-6), or severe (7-10). We conducted a subgroup analysis of patients with CRC, comparing SPPADE symptoms on an initial survey, regardless of timing in treatment course, between patients with eoCRC and aoCRC. Results: Patients with CRC (n=4281) completed a survey between March 2019 and December 2022. Patient demographics and SPPADE symptoms are reported in the table. Patients with eoCRC were more likely to report severe sleep disturbance (p,0.0001), pain (p=0.03485), anxiety (p,0.0001), emotional distress (p,0.0001), and fatigue (p=0.01083). In patients with eoCRC, women were more likely to report severe pain (12.6% vs 6.9%, p=0.0069), anxiety (16.1% vs 10.0%, p=0.012), emotional distress (12.1% vs 5.4%, p=0.00066), fatigue (18.9% vs 13.4%, p=0.038), and physical function impairment (10.1% vs 5.8%, p=0.026) compared to men. Conclusions: Patients with eoCRC reported higher symptom severity than patients with aoCRC. This suggests unique needs for symptom management in patients with eoCRC. Additional research is needed to evaluate how time since diagnosis, disease characteristics, cancer-directed treatment patterns, and cooccurring symptoms are associated with specific symptoms in this population. Research Sponsor: National Cancer Institute of the National Institutes of Health.

32 Poster Session

Applying the fragility index to randomized controlled trials evaluating total neoadjuvant therapy for rectal cancer. First Author: Tyler McKechnie, McMaster University, Hamilton, ON, Canada Background: A relatively novel summary measure that is not commonly reported in randomized controlled trials (RCTs) is the fragility index (FI). FI describes the number of additional events required for an outcome to lose statistical significance. It has been applied to a number of medical subspecialities such as critical care, orthopedic surgery and colorectal surgery. Recently, there has been significant interest in, and adoption of, total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC). A number of RCTs have assessed TNT, but the robustness of these practice changing RCTs has never been evaluated. As such, we designed the present study to assess the robustness of the RCTs evaluating TNT for LARC using the FI. Methods: Relevant articles were identified through a recently published review article by Johnson et al. in the Canadian Journal of Surgery, that narratively reviewed all of the previously published RCTs evaluating TNT for LARC. We manually searched Google Scholar and PubMed to identify any other relevant RCTs. Outcomes within these RCTs that were either dichotomous outcomes or time to event outcomes were eligible for inclusion if the reported effect size had an associated p-value of less than 0.05. The main outcome was the FI for each statistically significant outcome. Walsh et al.'s method of calculating FI was utilized. A RCTs results were considered fragile if the FI was less than the loss to follow up for a given outcome.

Correlations between FI and research characteristics were assessed using the Spearman's rank correlation coefficients. Results: Ten RCTs were identified with 25 outcomes having statistically significant differences between groups (p-values , 0.05).

Eleven outcomes were time-to-event outcomes, while the remainder were dichotomous outcomes. About half (n=13) were oncologic outcomes (i.e., survival, recurrence), while the rest (n=12) were short-and long-term complications. The median FI was 2 (interquartile range [IQR] 1-16). The number of patients lost to follow-up exceeded the FI in 17 outcomes (68.0%) and thus these results were considered "fragile". Lower FI was associated with high risk of bias (rho=-0.5594) and higher loss to follow-up (i.e., greater than 5% vs. less than 5%) (rho=-0.4394), while higher FI was associated with large sample size (i.e., greater than 500 patients vs. less than 500 patients) (rho=0.5120).

The robustness of outcomes from trials assessing TNT for LARC was found to be questionable. Most of these outcomes were fragile, as determined by the FI.

In most cases, two or less additional events would have resulted in a loss of statistical significance of the reported results. Those using the results of these studies, including clinicians and health policy experts, should apply caution when interpreting these types of trials. Research Sponsor: None.

8s COLORECTAL CANCER

Background: Trifluridine/tipiracil (FTD/TPI) is a standard of care therapy for patients with refractory metastatic colorectal cancer (mCRC). Recently, FTD/TPI in combination with bevacizumab (BEV) was also approved in this setting based on outcomes from the phase 3 SUNLIGHT trial, including statistically significant improvements in overall survival (OS) compared with FTD/TPI. This study examined demographic/clinical characteristics, treatment duration, OS, and healthcare resource use (HCRU), including outpatient/emergency room (ER) visits and hospitalizations, among patients with mCRC receiving FTD/TPI+BEV versus FTD/TPI in a real-world setting. Methods: This was a retrospective study of adults with CRC, who initiated FTD/TPI as monotherapy or in combination with BEV, identified from the Cerner Enviza electronic health records (EHR) database (12/2020-06/2023). A manual chart review of patients' medical records was conducted where last follow-up was defined as death or last encounter in the EHR. Descriptive statistics were reported for all study variables; Kaplan Meier curves were used to estimate OS. Results: Of 197 patients abstracted, 122 (62%) received FTD/ TPI+BEV combination therapy and 75 (38%) FTD/TPI monotherapy. Mean age was similar between the FTD/TPI+BEV and FTD/TPI groups (60.2 y vs 61.8 y) and 66% vs 63%, respectively, were male. Mean Charlson Comorbidity Index was 8.9 for the FTD/TPI+BEV group vs 8.5 for the FTD/TPI group and body mass index was 26.9 kg/m 2 vs 27.3 kg/m 2 , respectively. Most patients received treatment in the third or fourth line (65% FTD/TPI+BEV; 75% FTD/TPI). Median followup was 5.3 and 4.6 mo, respectively. Mean duration of treatment was 3.7 vs 2.7 mo for FTD/ TPI+BEV vs FTD/TPI monotherapy (Table ). Median OS (from FTD/TPI initiation to death) was 11.5 and 9.6 mo for FTD/TPI+BEV and FTD/TPI groups (number of deaths: 38 and 22), respectively. Patients receiving FTD/TPI+BEV had numerically more outpatient visits (20.5 vs 13.9), but similar ER visits (0.5 each) and slightly fewer hospitalizations (1.1 vs 1.2) compared with FTD/TPI, during follow-up. Overall HCRU costs were similar between groups (27,175 vs 27,891) . Conclusions: This real-world study supports the value of FTD/TPI+BEV combination therapy vs FTD/TPI monotherapy as seen in the SUNLIGHT trial. Patients with FTDTPI+BEV were treated for longer duration with improved OS and no difference in trends for HCRU and associated costs. Research Sponsor: Taiho Oncology, Inc.

Treatment outcomes among patients receiving FTD/TPI+BEV and FTD/TPI.

Characteristic FTD/TPI+BEV (N=122)

FTD/TPI (N=75)

Length of treatment, mean (mo) 3.7 2.7 OS, median (mo) 11.5 9.6 Outpatient visits, mean (n) 20.5 13.9 ER visits, mean (n) 0.5 0.5 Hospitalizations, mean (n)

1.1 1.2 Healthcare event costs, mean ($) 27,175 27,891

35 Poster Session

Use of novel cancer staging model to analyze healthcare costs of commercially insured patients with colorectal cancer. First Author: Rebecca Smith, Milliman, Inc., New York, NY

Background: Earlier colorectal cancer diagnosis can improve patient outcomes, but the payer cost impact of earlier stage at cancer diagnosis is not well understood because stage information is not directly available in administrative claims data. This data gap impairs researchers' ability to fully evaluate the financial impact of earlier neoplasia detection resulting from colorectal cancer screening. In prior work, we used SEER-Medicare data to develop machine learning algorithms to assign AJCC stages to colon (CC) and rectal (RC) cancer patients using treatment flags derived from claims data. These algorithms were 83% (CC) and 69% (RC) accurate at assigning incident cancer patients to their SEER-recorded AJCC stage. This new work applied those validated algorithms to commercial claims data to study the healthcare costs by stage of patients identified with incident CC or RC. Methods: Newly diagnosed CC and RC patients were identified in Milliman's 2019-2020 Consolidated Health Cost Guidelines Sources Data for commercially insured patients. Patients were assigned a cancer stage using a claims-based predictive multinomial logistic regression model (R Statistical Software -v4.1.2 R Core Team 2021; nnet package -Venables and Ripley 2002). Allowed medical and pharmacy costs were summarized by month, starting from each patient's initial claim with a cancer diagnosis through the end of the patient's enrollment or through September 2022. Patients with each cancer type were then grouped by stage, and mean cumulative costs at 12-, 24-, and 36months were calculated. Results: CC patients with stage 4 disease incur costs over 4x greater than those with stages 2B or lower and 1.7x greater than patients with stages 2B/3 during the first year after diagnosis. Cost differentials by stage are smaller among patients with RC. RC patients with stage 4 disease incur costs 2.2x greater than those with stages 2B or lower and 1.3x greater than patients with stages 2B/3 over the first year after diagnosis. For both CC and RC, substantial differences in cost persist over a 3-year period post-diagnosis. Conclusions: We applied a novel cancer staging model to commercial claims to estimate patients' healthcare costs by stage at diagnosis. CC and RC patients' costs increase substantially as their stages at diagnosis increase. In addition to improving patient outcomes, diagnosis of CC and RC at earlier stages among commercial patients could reduce treatment costs. Research Sponsor: Exact Sciences Corporation.

43 Poster Session

The efficacy of chemotherapy for colorectal cancer with early recurrence after adjuvant chemotherapy. First Author: Dai Okemoto, Osaka Medical and Pharmaceutical University, Takatsukisi, Osaka, Japan Background: Adjuvant chemotherapy is the standard treatment for patients with stage III colorectal cancer (CRC) underwent surgery.However, the efficacy of chemotherapy for early recurrence after adjuvant chemotherapy remains unclear. This study aimed to assess the efficacy of chemotherapy for CRC with early recurrence during or after adjuvant chemotherapy. Methods: We retrospectively reviewed CRC patients who underwent surgery at 3 institutions between 2016 and 2021. The inclusion criteria were as follows: ECOG performance status was 0 or 1, histology was adenocarcinoma, patients who received adjuvant chemotherapy following surgical resection, early recurrence during or within 12 months after adjuvant chemotherapy and no prior treatment for CRC after early recurrence. The interval from the last administration of adjuvant chemotherapy to recurrence was defined as the recurrence-free interval (RFI). Overall survival (OS), progression-free survival (PFS), objective response rates (ORR), and disease control rate (DCR) were assessed according to the RFI. Results: Of 448 patients, 32 patients were eligible. Median age was 57 years (range 26-79), 14 patients (44%) were male and ECOG performance status 0 / 1 was 29 (91%) / 3 (9%). RAS wildtype / mutant was 12 (38%) / 20 (62%) and right / left as sidedness was 21 (66%) / 11 (34%). Regarding adjuvant chemotherapy, 4 patients (12%) received single-agent therapy, while 28 patients (88%) received combination therapy with two agents. Palliative chemotherapy after early recurrence included Oxaliplatin-based regimens in 13 patients (41%), irinotecan-based regimens in another 13 patients (41%), and other regimens in 6 patients (18%). For all patients, the median PFS and OS were 10.4 months and 43.0 months, respectively. The ORR and DCR were 34.4% and 75.0%, respectively. When patients were divided into RFI , 6 months and RFI $ 6 months, the ORR was superior in the RFI $ 6 months group to RFI , 6 months group (56 % vs. 26%). The PFS (median 10.4 months vs. 17.8 months, HR 0.92; 95% Cl 0.36-2.38, p = 0.87) and OS (median 31.3 months vs. 43.0 months, HR 0.97; 95% Cl 0.31-3.08, p = 0.97) did not differ between the RFI , 6 months group and the RFI $ 6 months group. Multivariate analysis for OS indicated a trend toward a poor prognosis in the RFI , 6 months group compared to the RFI $ 6 months group (HR 1.78; p = 0.48) . Conclusions: In patients with CRC experienced early recurrence, the RFI , 6 months group had a trend of poor efficacy compared to the RFI of $ 6 months group. Research Sponsor: None.

44 Poster Session

Incidence patterns of colorectal cancer in Norway 1993-2022 by age, site, and morphology. First Author: Mari Fjørtoft Ystgaard, Oslo University Hospital, Oslo, Norway

Background: The incidence of colorectal cancer (CRC) has decreased or stabilized in most highincome countries, but an alarming increase is observed in younger adults. Norway has high CRC incidence, which increased until the past two decades, then stabilized. A national screening program started in 2022; hence, this study is on a screening-naïve population. We aim to describe up-to-date incidence patterns of CRC, with emphasis on age-specific differences in tumor site and morphology. Methods: We extracted data on all CRC cases diagnosed 1993 to 2022 from the Cancer Registry of Norway, with completeness estimated to be .99%. Data was stratified by age groups (20-49, 50-74, and $75) , sex, primary tumor location and morphology. Age-adjusted incidence rates were calculated using Stata 17 and analyzed using Joinpoint regression to provide annual percentage change (APC) and average annual percentage change (AAPC) of incidence rates. Results: There were 107 524 cases eligible for analysis. In the age group $75, overall incidence increased (AAPC 0.8), mainly caused by right-sided colon cancer (RCC), which increased until 2016 (APC 2.5), followed by a slight decrease (APC -0.9). The age group 50-74 had stable incidence (AAPC -0.2). Incidence in the age group 20-49 increased (AAPC 1.3), caused by left-sided colon cancer (LCC) and rectal cancer (RC). When stratifying on morphology, incidence of mucinous carcinomas was stable (AAPC -0.6), approx. 10% of all CRC cases. Neuroendocrine neoplasms (NEN) increased in all age groups (AAPC 4.2), accounting for only 1.4% of all CRC cases; but contributed somewhat to the overall incidence in age group 20-49, in particular RC where 8.8% of cases were NEN. In the age group 20-49, adenocarcinomas had an AAPC of 1.4, mucinous carcinomas -0.8, and NEN 4.1. Conclusions: We found an increasing incidence of CRC in the youngest (,50) and elderly ($75). LCC and RC incidence increased in the youngest age group, still increasing up until 2022. In contrast, the increase in the elderly was mostly due to RCC. Different incidence patterns of primary tumor locations in younger and older age groups may imply differences in etiology and prognosis, different biological features and possibly therapeutic implications. Research Sponsor: None.

Age-standardized incidence (ASR) per 100 000 and AAPC for all CRC 1993-2022 stratified for age groups and primary tumor site.

Age

COLORECTAL CANCER 11s

Visit meetings.asco.org and search by abstract for the full list of abstract authors and their disclosure information. initial diagnosis; 29% had a KRAS mutation (at any time #30 days post-index; 35% not tested). Median time from mCRC diagnosis to index was 35 days. Most common 1L regimens were FOLFOX 6 bevacizumab (48%), FOLFIRI 6 bevacizumab (15%), and capecitabine (13%). Median follow up from index date was 15.6 months (mos); 60% died. LDH testing was performed in 2,547 pts (17%) during baseline and 3,379 pts (22%) post-index. Among those with $1 LDH test during each line of therapy (LOT), median number of LDH tests per pt was 4-6 and median time from line initiation to first LDH test was 7-10 days across the first five LOTs (Table ). Among LDH tested pts during follow-up (n=3,379), 21% and 40% had abnormal and normal LDH values at baseline, respectively (39% missing). Demographic characteristics of abnormal vs normal LDH pts were similar; abnormal LDH pts were more likely to be $65 years (52% vs 49%), African American or Black (12% vs 7%), and reside in the Northeast (30% vs 21%). Median OS (95% CI) in pts with normal vs abnormal baseline LDH was 29.9 (28.3, 31.7) mos vs 16. 8 (14.8, 18. 2) mos. In multivariate Cox proportional-hazards model, pts with abnormal baseline LDH values had higher risk of death (HR 1.91, p,0.0001) after adjustment for pt demographic and clinical characteristics. Conclusions: In RW clinical practice in the USA, only one-fifth of mCRC pts receiving CT undergo LDH testing even though LDH value has been found to be a prognostic factor of OS. Efforts to increase LDH testing may help guide treatment decisions in this setting. Research Sponsor: Bayer. Background: In the phase 2 ReDOS study, REG first-cycle dose-escalation showed comparable activity and lower incidence of adverse events in pts with mCRC vs standard dosing. This retrospective cohort analysis aimed to examine RW dosing patterns of REG and associated duration of treatment (DoT) in pts with mCRC in Europe. Methods: Data from pts with mCRC, aged $18 years who initiated REG monotherapy from January 1, 2019 to April 30, 2022, were collected retrospectively from chart review by physicians recruited from the IQVIA OneKey database. Pts were categorized by dosing regimen to either flexible dosing regimens (ReDOSlike [,160 mg starting dose] or dose-adjusted [160 mg starting dose with dose adjustments during treatment] ) or a standard dosing regimen (160 mg throughout treatment).

Results: Overall, 355 pts (France, n=146; Italy, n=143; Belgium, n=66; 68% male, 54% aged $65 years) were eligible for inclusion. Nearly half (49%) received a ReDOS-like regimen, 32% received a standard dosing regimen, and 19% received a dose-adjusted regimen (Table ). A higher proportion of pts on a dose-adjusted regimen had $3 metastatic sites (64% vs 43% for standard dosing) and most had initiated $3 REG cycles (93% vs 67% and 64% for ReDOS-like and standard dosing regimens, respectively). Pts receiving a ReDOS-like dosing regimen had worse performance status (ECOG PS $2, 35% vs 30% for dose-adjusted and standard dosing) and a higher proportion of KRAS (42% vs 37% and 30% for dose-adjusted and standard dosing regimens, respectively) or NRAS (28% vs 24% and 21% for dose-adjusted and standard dosing regimens, respectively) mutations. Median DoT was longer for ReDOS-like and dose-adjusted regimens vs standard dosing (1.4 and 1.9 vs 1.0 months, respectively; Table ). Conclusions: Pts receiving REG flexible dosing regimens (ReDOS-like, dose-adjusted) had longer DoT compared with a standard dosing regimen despite having a higher frequency of adverse prognostic factors. Thus, this study affirms that flexible dosing strategies are viable options for optimizing REG treatment and outcomes in pts with mCRC. Research Sponsor: Bayer.

48 Poster Session

Real-world (RW) study in patients (pts) with metastatic colorectal cancer (mCRC) with long-term responses to regorafenib in the USA. First Author: Richard D. Kim, Moffitt Cancer Center, Tampa, FL Background: Anecdotal evidence suggests that some pts with mCRC experience significantly longer responses to REG in clinical care settings, including a case exceeding 9 years. However, comprehensive studies on long-term responders to REG are lacking. We evaluated demographic/ clinical characteristics of pts with long-term response (LTR) to REG using duration of treatment (DOT) as a surrogate for treatment response. Methods: This was a retrospective cohort study using the US nationwide de-identified Flatiron Health Electronic Health Record-derived database.

The study period was January 1, 2013 to May 31, 2023, and adult pts with mCRC who initiated REG monotherapy (index date) from July 1, 2013 to December 31, 2022 were included. DOT for pts with LTR of $5 months (LTR5 [primary objective]; mos) or $4 mos (LTR4 [secondary objective] ) were determined. Results: A total of2,326 eligible pts (median age 64 yrs; 56% male) had initiated REG during the study period. Overall, 346 pts (15%; median age 65 yrs) had LTR5 and 503 pts (22%; median age 65 yrs) had LTR4. Among pts with LTR5, 46% had stage IV disease at initial diagnosis, 68% had ECOG performance status (ECOG PS) 0-1 at index, 64% received prior bevacizumab (BEV), and of pts tested at index with results, the median carcinoembryonic antigen (CEA) level was 35 ng/mL, and 51% and 5% had a KRAS and BRAF mutation at index, respectively; pts with LTR4 had similar characteristics (Table ). Median time from initial CRC diagnosis to index date was 39.2 mos for pts with LTR5 and 38.6 mos for pts with LTR4. Of pts who initiated REG before 2019 (n = 1,070), 14% had LTR5 and 21% had LTR4; of pts who initiated REG from 2019 onwards (n = 1,256), 16% had LTR5 and 22% had LTR4. Among pts with LTR5, 33% and 23% had received REG as third-line (3L) or fourth-line (4L) treatment, respectively; among pts with LTR4, 34% and 23% had received REG as 3L or 4L treatment, respectively. Median time to discontinuation of REG was 7.3 (95% CI 6.9, 7.8) mos in pts with LTR5 and 6.0 (95% CI 5.7, 6.2) mos in pts with LTR4. Median follow-up time (from index date) was 13.3 mos and 11.1 mos in pts with LTR5 and LTR4, respectively. Conclusions: This is the first large-scale RW evidence study to describe demographic/ clinical characteristics of pts with LTR to REG. Pts demonstrating LTR typically had favorable ECOG PS at REG initiation, less advanced disease at initial diagnosis, and the majority had received prior BEV. Research Sponsor: Bayer.

Reproductive and fertility-related challenges in female patients diagnosed with early-onset colorectal cancer. First Author: Rachel M. Seifert, University of Utah, Salt Lake City, UT Background: Incidence of early-onset colorectal cancer (EOCRC, defined as onset ,50 years) is on the rise, with rates increasing by 51% from 2000-2015. Knowledge of fertility concerns in patients with EOCRC is important to provide the resources needed for this group. The aim of this study is to examine reproductive concerns after cancer diagnosis in female COLONTOWN patients with EOCRC using a validated and standardized questionnaire "Reproductive Concerns After Cancer" (RCAC). Methods: Female survivors (N=89, age at diagnosis 20 to 47 years) with EOCRC diagnosis were recruited from COLONTOWN. In order to capture the impact of EOCRC diagnosis on sexual health and fertility, a 51-question survey was created that included the RCAC scale as well as questions about pregnancy history, whether fertility preservation counselling occurred, self-reported demographics, and tumor and treatment. RCAC includes 6 subdomains on fertility preservation, partner disclosure of fertility status, child's health, personal health, acceptance of possible infertility, and becoming pregnant, with total score being the sum of these domains. Data collected was analyzed using means, ranges, and standard deviations for continuous variables and frequencies and chi squared tests for categorical variables. Results: The mean age at diagnosis was 35 6 5 years. 72% had discussions with a medical professional about fertility preservation after receiving their cancer diagnosis. Patients with rectal cancer were more likely to have this discussion compared to patients with colon cancer (p=0.04); tumor stage did not affect likelihood of having a fertility discussion (p.0.05). Seventeen (19%) underwent subsequent fertility preservation. Patients with stage IV cancer were less likely to undergo fertility preservation compared to those with stage I-III cancer (p=0.02); the decision to undergo fertility preservation was not affected by tumor site (p.0.05). 13% of all patients had insurance that would cover fertility preservation. Notably, 33 (37%) of patients said they would have considered fertility preservation if it were covered by insurance, and this was not impacted by tumor site or stage (p.0.05). RCAC subcategory scores were 3.47 for fertility preservation, 2.50 for partner disclosure of fertility status, 4.09 for child's health, 3.88 for personal health, 2.27 for acceptance of possible infertility, and 3.49 for becoming pregnant. Conclusions: This study provides evidence that some patients with EOCRC experience concerns about fertility. Patients endorsed concern for child's health and personal health, followed by concerns about becoming pregnant and fertility potential. Interestingly, 37% would have considered fertility preservation had it been covered by insurance. This study provides characterization of the fertility-related concerns of EOCRC survivors and supports the future development of resources and policies to support these patients. Research Sponsor: Utah Grand Challenges Grant.

58 Poster Session

Risk of relapse after surgical resection of localized appendiceal adenocarcinoma. First Author: Mohammad Mahdi Fanaeian, The University of Texas MD Anderson Cancer Center, Houston, TX Background: Appendiceal adenocarcinoma (AA) encompasses a heterogenous mix of histologic subtypes and frequently presents with peritoneal metastases. Data regarding the risk of relapse after surgical resection in patients with localized AA (stages I-III) is limited. More accurate evaluation of features predictive of relapse is critical to counsel patients, determine follow-up, and guide decisions regarding adjuvant therapy. Methods: The Foundry software platform was used to query the MD Anderson Cancer Center (MDA) Electronic Health Record database to identify and extract clinical information from AA patients presented to MDA from 2004 to 2023. Results: We identified 296 patients with localized AA, split into two cohorts: patients who underwent surgery at MDA (n=133) and patients with surgery at an outside institution later referred to MDA (n=163). The most common histologic subtypes were mucinous (n=124, 41.9%) and goblet (n=121, 40.9%) with less frequent colonic-type (n=42, 14.2%) and signet ring cell (SRC, n=9, 3%) . With a median follow-up of 47 months, the relapse rate (RR) for the MDA surgical cohort was only 6% (n=8), with a median time to relapse of 24 months (range=8-74). Evaluating all 296 localized AA patients, histologic subtype was significantly associated with risk of relapse, with goblet AAs having lowest risk (6%, n=7), followed by colonic-type (12%, n=5), mucinous (27%, n=33), and SRC (44%, n=4; overall P, 0.001), with a median time of relapse of 26 months (range=3-96). Patients with a positive LN, higher grade, and/or higher T stage showed a higher RR (Table ). Use of adjuvant chemotherapy (AC) was not associated with RR in our cohort, with odds ratio trending towards increased risk of relapse ( 14

59 Poster Session

Survival benefit and clinical characteristics of patients with metastatic colorectal cancer (mCRC) receiving pulmonary metastasectomy. First Author: Javier Soto Alsar, Hospital General Universitario Gregorio Mara ñón, Instituto de Investigaci ón Sanitaria Gregorio Mara ñón, Madrid, Spain Background: The role of lung metastasectomy in mCRC remains a topic of particular controversy, being uncertain which patients benefit more from it and whether it leads to better survival outcomes. Our aim was to identify clinical and molecular differences and survival data in a cohort from a tertiary care hospital. Methods: We retrospectively analyzed 115 patients with lung metastases from colorectal cancer (CRC) in a tumor registry from 2015 to 2021, analyzing clinical and molecular characteristics, as well as overall survival (OS) data of patients who received lung metastasectomy versus patients who did not. Results: Among all patients, 36 (31.3%) received pulmonary metastases surgery. Patients undergoing metastases resection had more frequently ECOG 0 (51.4% vs 20.8%, p = 0.0011), resected primary tumor (100% vs 78.5%, p = 0.0026), metachronous metastatic disease (75% vs 46.8%, p = 0.0048) and a single metastatic location (79.4% vs 41%, p = 0.0002). In addition, none of them had BRAF mutation (0% vs 17.1%, p = 0.04); however, no statistically significant differences were found regarding KRAS, NRAS, PI3K, HER2 or presence of microsatellite instability (MSI). Patients who received lung metastasectomy had higher BMI (26.1 vs 24.4, p = 0.037) and lower mean levels of CEA (19.5 vs 142.9, p = 0.007), CA 19.9 (30.6 vs 244.9, p = 0.011) and LDH (159 vs 211.9, p = 0.018). We found an OS benefit in patients undergoing metastatic surgery (median not reached (NR) vs 41.4 months, HR for death 0.27, 95% CI, 0.14 -0.53, p , 0.000); a multivariate analysis confirmed that this benefit was independent from the characteristics mentioned above. The median progression-free survival (PFS) after metastases resection was 53.3 months. Conclusions: In our study, patients who were more likely to receive lung metastasectomy were those with ECOG 0, resected primary tumor, metachronous disseminated disease, a single metastatic location, native BRAF mutation status and low CEA, CA 19.9 and LDH levels, with a significant OS benefit associated.

60 Poster Session

Clinical characteristics and survival analysis in patients with isolated pulmonary metastases from colorectal cancer (CRC). First Author: Javier Soto Alsar, Hospital General Universitario Gregorio Mara ñón, Instituto de Investigación Sanitaria Gregorio Mara ñón, Madrid, Spain Background: Recent studies seem to indicate that patients with metastatic colorectal cancer (mCRC) with exclusive pulmonary metastatic disease have better outcomes than those with other metastatic sites. The aim of this study is to identify differences in clinical and survival characteristics between the two groups in a cohort of a third level hospital. Methods: We retrospectively analyzed a sample of 569 patients with mCRC in a tumor registry from 2015 to 2021, studying clinical and molecular characteristics, as well as overall survival data of patients with isolated pulmonary metastases, versus the rest of patients. Results: Of the total sample analyzed, 61 patients (10.7%) had isolated pulmonary metastases. In these patients, several clinical characteristics were more frequent: primary rectal tumor (52.5% vs 23.4%, p , 0.000), resected primary tumor (95.1% vs 78.9%, p = 0.0026), metachronous metastatic disease (62.3% vs 42%, p = 0.0025) and complete response rate to the first line of treatment (19.3% vs 9.9%, p = 0.026). Furthermore, analytically, these patients were more likely to have normal CEA (75% vs 38.3%, p , 0.000), CA 19.9 (84.3% vs 57.7%, p = 0.0002) and LDH (91.1% vs 66.5%, p = 0.0007) levels. In our cohort, we found no statistically significant differences in tumor mutational status (KRAS, NRAS, BRAF, PI3K and HER2). There were no patients with exclusive pulmonary metastatic disease and microsatellite instability (MSI). 70.3% of patients with isolated pulmonary metastases received lung metastasectomy, and up to 58.3% received a second metastases surgery. We also found a numerical benefit in terms of overall survival (OS) in patients with exclusive metastatic lung disease, although it did not reach statistical signification (median OS 77.3 vs 58.1 months, HR for death 0.70, 95% CI, 0.49 -1.01, p = 0.083). Conclusions: In our cohort, patients with isolated pulmonary metastases were more likely to have rectal tumors, primary tumor resection, metachronous metastatic disease, higher rate of complete responses and normal CEA, CA 19.9 and LDH levels, with a possible benefit in terms of OS. Research Sponsor: None.

Real-world impact on overall survival of oxaliplatin-based adjuvant chemotherapy in older patients with colorectal cancer in Mexico. First Author: Marytere Herrera, Gastrointestinal Oncology Unit, Mexico City, Mexico Background: Colorectal cancer (CRC) is one of the most commonly diagnosed cancer both in Mexico and worldwide, with the peak incidence in patients .65 years. The use of adjuvant chemotherapy (CT) improves the prognosis of high-risk CRC. The benefit from fluorouracil (FU)-based CT across all age groups is not questionable, but the use of oxaliplatin (Ox) is controversial. Methods: Original, retrospective, observational study. Included patients diagnosed with CRC adenocarcinoma treated at the Instituto Nacional de Cancerología México, between 2004 to 2022. Statistical analysis required: X 2 and ttest, Kaplan Meier, Log Rank, and Cox Regression. Statistical significance differences were assessed when p was bilaterally ,0.05. Results: From 1,238 patients with localized CRC, 275 patients were included in analysis and divided into 2 groups: young (# 30 years) (n = 54), and older ($ 70 years) (n = 221). Most patients were female for both groups (55%). Comorbidities were observed in 2% of young patients and 51% of older patients (p , 0.001). Stages (S) were: II (31%; 39%), and III (59%; 47%). CT was received in 70% of young and 47% of older patients (p = 0.002). Regarding CT regimens, 56% and 21% of young and older patients respectively, had oxaliplatin (p , 0.001), while 21% of young and 32% of older patients did not complete the CT (p = 0.012). Overall survival (OS) analysis was performed considering age and S. S-II median-OS was not reached (NR) for both groups, while S-III median-OS was 170 months (m) for young versus NR for older (p = 0.690). When including CT in OS analysis, patients S-II median-OS was NR for all groups (p = 0.081), while S-III median-OS was 170 m with and 19 m without CT for young versus NR with and 89 m without CT for older, respectively (p = 0.010, 95% CI 0.059-0.123). In S-III older patients, a sub-analysis was performed considering Ox: 10-year-OS was 71% versus 60% for patients treated with and without Ox respectively (p = 0.030, 95% CI 0.25-0.93). In Cox-Regression analysis for patients with clinical stage III, regimen completion (p = 0.004; HR 0.38, 95% CI 0.201-0.745) and Ox (p = 0.022; HR 0.423, 95% CI 0.203-0.881) remained as predictor factors of OS. Conclusions: There are no studies which compare the administration of CT between young and older patients or the description of these populations in Mexico. Young patients are more likely to receive CT with Ox assumingly due to the lack of comorbidities and life expectancy. The benefit of CT on OS in young patients is not in question. An increase in OS was found in older patients who received CT with Ox, but a higher percentage of treatment discontinuation secondary to toxicity. As recommended by the literature, its essential to integrate assessment in older patients to determine which patients will benefit from complete CT regimens to increase their OS, apart from their chronological age. Research Sponsor: None.

62 Poster Session

Real-world comparison of low-versus high-dose continuous 5FU infusion in patients receiving triplet chemotherapy plus bevacizumab for newly diagnosed metastatic colorectal cancer (mCRC). First Author: William Joseph Chapin, Abramson Cancer Center at the University of Pennsylvania, Philadelphia, PA Background: Several randomized trials demonstrated an overall survival (OS) benefit to triplet chemotherapy (5-FU, oxaliplatin, and irinotecan) plus bevacizumab compared to doublet chemotherapy plus bevacizumab in patients with newly diagnosed mCRC, though with higher rates of neutropenic fever and diarrhea. These trials used high-dose continuous infusion 5-FU (3,200 mg/m2/48 hours), but national guidelines suggest lowdose continuous infusion 5-FU (2,400mg/m2/48 hours) due to lower tolerance in U.S. patients. We performed a retrospective cohort study in a U.S. population to compare the effectiveness of low-vs high-dose continuous infusion 5FU in patients undergoing triplet chemotherapy plus bevacizumab for newly diagnosed mCRC. Methods: We used the nationwide Flatiron Health electronic health record-derived database, comprising deidentified patient-level structured and unstructured data curated via technology-enabled abstraction from ~280 cancer clinics. Patients with newly diagnosed mCRC who initiated triplet chemotherapy plus bevacizumab between 10/23/14 and 10/31/22 with non-missing height, weight, and dosing data were included. 5FU infusion doses of 2,000 -2,799 mg/m2 were categorized as low-dose while those ./= 2,800 mg/m2 were categorized as high-dose. OS from first-line treatment initiation was assessed by dosing group using the Kaplan Meier method with log-rank testing. Multivariable analysis with adjustment for pre-specified variables with imbalance (defined by standardized difference , -0.10 or . 0.10) was performed using multivariable Cox proportional hazards modeling. Missing data were imputed using multiple imputation with chained equations. Results: Among 320 patients included, 244 received low-dose and 76 patients received high-dose continuous infusion 5FU. Imbalance between low-and highdose groups was observed in the use of 5FU bolus (23% vs 3%), year of metastatic diagnosis 2018 -2022 (80% vs 55%), mean irinotecan dose (156.4 vs 160.5 mg/m2), leftsided primary (73% vs 64%), MMR deficiency (3% vs 6%) and mean CEA (478 vs 691 mg/ L). In univariate analysis, median OS was 33 months (95% CI 26 -39) in the low-dose group compared to 34 months (95% CI 24 -48) in the high-dose group (HR 1.16; 95% CI 0.79 -1.69; p = 0.44). After adjusting for imbalanced covariates, there was no difference in hazard of death between low-and high-dose groups (HR 0.99; 95% CI 0.64 -1.53; p = 0.97). Conclusions: In this real-world, U.S. population with newly diagnosed mCRC receiving triplet chemotherapy plus bevacizumab, there was no association with survival between low-vs high-dose continuous infusion 5FU. This supports current guidelines recommending low-dose continuous infusion 5FU (2,400mg/m2/48 hours) for patients with mCRC receiving triplet chemotherapy in the U.S. Research Sponsor: None.

63 Poster Session

Retrospective analysis of the real-world demographics, clinical characteristics, and treatment patterns in metastatic CRC among patients treated with encorafenib in combination with cetuximab in the United States. First Author: Aparna Raj Parikh, Massachusetts General Hospital Cancer Center, Boston, MA Background: The presence of BRAF V600E mutations (BRAF-m) occurs in approximately 7% of patients with metastatic CRC (mCRC). Encorafenib (enco) plus cetuximab (cetux) were approved in April 2020 as the first targeted therapy for the treatment of adult patients with BRAF-m mCRC. The purpose of this study is to assess the demographics, clinical characteristics, and treatment patterns in BRAF-m mCRC among patients treated with enco, based on a claims database in the US. Methods: This was a retrospective cohort study in the IQVIA PharMetrics Plus claims database. Adults $18 years old with $1 claim for enco (first claim for enco on/after 4/1/2020) with concurrent cetux, as approved, or with EGFR panitumumab (pani), $2 ICD-9/10 codes for malignancy of the colon or rectum $30 days apart in the 1 year before index date, and $1 day of pharmacy and medical continuous enrollment during the index date were included. Patients were excluded if they had a record of melanoma or non-small cell lung cancer during the year before index date, were enrolled in a clinical trial any time after the CRC diagnosis date or did not have a treatment regimen starting on or after CRC diagnosis date. Index date was the date of first treatment of enco+EGFR during the identification period (4/1/2020-3/31/2022). Patient demographics and disease characteristics were assessed at baseline, and treatment patterns were evaluated during the pre-index and follow-up periods. Results: 125 patients were included. Median (Q1 [1 st quartile], Q3 [3 rd quartile] ) age at index was 58 (49, 63) years; 52.0% were female; 47.2% residents in the South, 26.4% in the Midwest, 14.4% in the East and 12.0% in the West. In terms of healthcare coverage, 64.0% were under commercial, 27.2% self-insured and 8.8% under Medicare plans. Most patients (60.8%) at the start of enco had metastases in 3 or more sites, predominantly in the liver (76.8%), lymph nodes (50.4%), and lung (43.2%). The 2011 Modified Quan Charlson Comorbidity Index was 0 for 44.8% of the patients, 1-2 for 39.2%, and 3 or more for 16.0%. Mean (SD [standard deviation]) number of pre-index treatment regimens was 0.87 (0.73). Among the enco patients who had a previous treatment computed in claims, FOLFOX +/-bevacizumab (beva) and FOLFIRI + beva were the most common. Among the ones who had a subsequent treatment computed in claims, FOLFIRI +/-beva was the most common. Conclusions: This study provides current RW demographics, disease characteristics and treatment patterns among BRAF mCRC patients treated with enco in the US. Research Sponsor: Pfizer.

64 Poster Session

Retrospective analysis of adherence and persistence of encorafenib in combination with cetuximab among patients with BRAF metastatic CRC in the United States (US). First Author: Aparna Raj Parikh, Department of Medicine, Division of Hematology & Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA Background: The BRAF V600E mutation (BRAF-m) occurs in approximately 7% of patients with metastatic CRC (mCRC). Encorafenib (enco) in combination with cetuximab (cetux) was approved in April 2020 as the first targeted regimen for the treatment of adult patients with mCRC with BRAF-m. The purpose of this study is to analyze the postapproval real-world persistence and adherence to treatment with enco in combination with cetux or with panitumumab (pani), an alternative EGFR, in mCRC, based on a claims database in the US. Methods: This was a retrospective cohort study in the IQVIA PharMetrics Plus claims database (2013) (2014) (2015) (2016) (2017) (2018) (2019) (2020) (2021) (2022) . Adults $18 years old with $1 claim for enco (first claim for enco on/after 4/1/2020) with concurrent EGFR (cetux or pani), $2 ICD-9/10 codes for malignancy of the colon or rectum $30 days apart in the 1 year before index date, and $1 day of pharmacy and medical continuous enrollment during the index date were included. Patients were excluded if they had a record of melanoma or non-small cell lung cancer during the year before index date, were enrolled in a clinical trial any time after the CRC diagnosis date or did not have a treatment regimen starting on or after CRC diagnosis date. Index date was the date of first treatment of enco + EGFR during the identification period (4/1/2020-3/31/2022). Patient demographics and disease characteristics were assessed at baseline, adherence (measured as at least 80% of days covered) and persistence (measured as time to discontinuation by Kaplan-Meier method) were estimated during the follow-up period. Results: 125 patients were included. Median (Q1 [1 st quartile], Q3 [3 rd quartile] ) age at index was 58 (49, 63) years and 52.0% were female. Metastases were present in 3 or more sites in 60.8% of the patients, in 1 or 2 sites in 37.6%. The 2011 Modified Quan Charlson Comorbidity Index was 0 for 44.8% of the patients, 1-2 for 39.2%, and 3 or more for 16.0%. Most patients received cetux as their EGFR combined with enco (77.6%). Adherence to enco + EGFR was high (85.6%); enco + cetux vs. enco + pani: 89.7% vs. 74.1%. Median (Q1, Q3) proportion of time on cetux while on enco was 87.9% (77.9%, 94.3%) and median (Q1, Q3) proportion of time on pani while on enco was 79.9% (70.0%, 90.0%). Median (95% confidence interval) time to enco regimen discontinuation during follow-up was 6.2 (4.9-8.8) months. Conclusions: This up-to-date study provides current real-world evidence on the use of enco + EGFR in mCRC BRAF-m patients in the US. The results show high levels of adherence to the treatment, suggesting high tolerability to encorafenib, and persistence consistent with clinical trial evidence. Research Sponsor: Pfizer.

Timing of primary tumor resection after systemic chemotherapy initiation among patients with metastatic colon cancer. First Author: Munir Buhaya, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX Background: In patients with resectable, metastatic colon cancer, the optimal timing of definitive resection of the primary tumor after initiation of chemotherapy remains unclear. Our goal is to identify factors that influence the interval between chemotherapy and definitive surgical management, and its impact on overall survival. We hypothesize that patients with shorter chemotherapy-to-surgery intervals (less than 60 days or about 2 months) compared to 61-180 days (2-6 months) or greater than 180 days (. 6 months), will have the worst overall survival. Methods: We conducted a retrospective analysis of all patients diagnosed with metastatic colon cancer from 2004-2016 who underwent resection of both primary tumor and distant metastatic site from the National Cancer Database (NCDB). Among those who received chemotherapy prior to surgery, we calculated the interval days between initiation of chemotherapy and primary tumor resection. Descriptive analysis, logistic regression, and overall survival was performed comparing patients with chemotherapy-to-surgery intervals of ,60, 60-180, and .180 days. Results: A total of 2,238 patients were included, of which 143 (6%), 1446 (65%), and 649 (29%) were in the ,60, 60-180, and .180 days groups, respectively. Similar distribution of patients across groups was observed for age, gender, insurance status, income, education level, distance travel, and Charlson-Deyo scores.

Poorly differentiated tumors were more frequent in the ,60 days group (12% vs 2-9% for other grades, p=0.001) as well as presence of lymphovascular invasion (8% vs 4%, p = 0.006). The odds of receiving care at an academic facility were lower in the ,60 days group (OR: 0.52, 95% CI 0.273-0.994). Overall survival was significantly reduced in the ,60 days group compared to 60-180 days (HR= 0.562, 95% C: 0.38-0.82).

Conclusions: In this retrospective study from a national database, shorter chemotherapy-to-surgery interval (,60 days) was associated with poorly differentiated tumors and lymphovascular invasion. The odds of receiving surgery in ,60 days of receiving chemotherapy was lower in academic/research facilities. A reduction in overall survival was observed in the shorter interval (,60 days) group compared to longer intervals. More research is needed to define the optimal chemotherapy-surgery interval and factors that influence this. Research Sponsor: None.

66 Poster Session

Multisite external validation of blood test for colorectal neoplasia screening in a majority average-risk screening cohort of 449 subjects. First Author: Shai Friedland, Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, CA Background: The FirstSight CRC screening blood test was previously shown to have sensitivities of 92.1% and 54.5% for CRC and AA at a specificity of 90.6% for 1,038 subjects from 18 clinical sites. In this report, we describe the independent external validation of the predefined FirstSight CRC screening blood test with new subjects from 16 sites dispersed across the US, 4 of which are new and did not participate in the previous study. Methods: The validation study included subjects from two sources: Average-risk, asymptomatic screening subjects from screening clinics supplemented with diseasedonly subjects from surgical oncology centers. Blood was drawn before bowel prep for colonoscopy or treatment. External validation as well as Monte Carlo cross-validation (MCCV) methods were used to evaluate the performance of the pre-defined FirstSight assay, algorithm, and clinical thresholds in this independent external validation set. Results include sensitivity and specificity to detect CRC and AA and 95% confidence intervals. Results: The study cohort (55.2% female; mean age 56.9 yrs.) consisted of 449 subjects (White 61.7%; Black 14.5%; Hispanic 18%; AAPI and Middle Easterners 5.8%). The majority of them, 376 (84%), were asymptomatic, average-risk screening subjects (including 1 CRC, 53 AA, and all 322 negative subjects). An additional 73 (16%) diseased subjects (39 CRC and 34 AA) were enriched due to low disease prevalence. The FirstSight algorithm derives a test score from 0 to 100 as a quantitative measure of AA and CRC risk with a cutpoint to assign a binary low-or high-risk designation. The previously described cutpoint of 47.2 yielded a test specificity of 90.0%, and 90.0% and 52.9% sensitivity for the detection of CRC and AA, respectively. Here we report a higher cutpoint 50 with identical sensitivities but improved specificity to 90.7%. Point estimates of sensitivity and specificity, including CRC staging, and Clopper-Pearson exact 95% confidence intervals based on the external validation results are presented below. Conclusions: An external validation included 449 subjects from a multi-site, majority average-risk CRC screening study successfully validated the FirstSight Blood Test's high performance as previously established with 1,038 subjects. The results bring forth confidence in the Test's reproducibility in a large-scale clinical trial. Clinical trial information: NCT05127096. Research Sponsor: None.

67 Poster Session

Trends in colorectal cancer screening from NHIS survey: Analysis of modalities impact on overall screening. First Author: Derek W. Ebner, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN Background: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality among men and women combined in the United States (US). Although the national screening rate has increased over the years, it remains below the target of 80% recommended by the National Colorectal Cancer Roundtable for improved CRC outcomes. In most recent years, and particularly during COVID-19, screening-eligible individuals preferred at-home, non-invasive screening options over invasive tests such as colonoscopy due to convenience and accessibility. The objective of this study was to understand the CRC screening trends over the last two decades, and the impact of various screening modalities on the overall CRC screening rate. Methods: Using National Health Interview Survey (NHIS) data from 2005 onwards, we examined CRC screening (colonoscopy, mt-sDNA, FIT/FOBT, and sigmoidoscopy) rates among adults aged 50-75 years. A pseudo-time-series cross-sectional (pseudo TSCS) analysis was conducted including random effects Generalized Least Square (GLS) regression model to estimate the relative impact of each modality on the overall increase in CRC rates from 2018 to 2021. Results: Among 50-75 years old individuals, the estimated CRC screening use increased by 32% from 2005 to 2021 (47.7% to 69.9%). Between 2018 to 2021, the rates increased from 64% to 70%, driven largely by increased use of mt-sDNA, a 62.1% increase from 2018 to 2021 (2.5% to 6.6%). During this time period, colonoscopy utilization increased by 4.4% (61.2% to 64.0%), while FOBT/FIT utilization increased by 3.6% (5.3% to 5.5%). A pseudo-TSCS analysis showed that mt-sDNA contributed substantially to the overall CRC screening rate increase during years 2018-2021 (77.3%; p , 0.0001). Conclusions: While CRC screening rates are increasing, they remain below the national goal of 80%. Mt-sDNA as a home-based, non-invasive screening, recommended at a 3-year interval, has been leveraged to improve overall CRC screening rates, particularly to address the screening backlog created during the COVID-19 pandemic. A collaborative approach between healthcare providers and screening-eligible individuals is needed to empower patients with choice for their CRC screening modality to achieve the national goal. Research Sponsor: Exact Sciences, Inc.

68 Poster Session

Enhanced blood-based colorectal cancer screening with improved performance in detection of early stage disease. First Author: Sven Duenwald, Guardant Health, Redwood City, CA Background: Blood based colorectal cancer (CRC) screening has been validated for use in average risk populations (ECLIPSE NCT#04136002; Guardant Health, USA). Here we present the performance of an enhanced version of a blood-based screening test developed to optimize detection of low shedding tumors by leveraging epigenomic features of cell-free DNA (cfDNA). Test performance was assessed across screenrelevant individuals from the intended use population, including a collection of screendetected CRC and enriched cohort of individuals with endoscopy finding of CRC. Methods: We trained a regression model to classify whether aberrant cfDNA originated from individuals with CRC or non-ACN individuals and compared performance to an original model in a fixed set of screen-relevant samples sequenced to a median of 11M reads per sample across a panel approximately 1Mb in size. Model optimization focused on identifying training settings and samples to maximize detection of low shedding screen-relevant tumors and introduced noise reduction techniques to minimize technical variation. The final enhanced model was trained in over 4500 samples; the calling cut-off was set targeting 90% specificity in the average-risk population following US-Census age distribution. Analytical Limit of Detection (LoD) was estimated using ~5,000 in silico dilution samples generated from blood samples from 25 CRCs and ~1,650 non-ACNs. Changing to either activity or inactivity at T6 or T12 was not significantly associated with allcause mortality (Table ). Conclusions: Maintaining a physically active lifestyle following surgery for stage I to IIA CRC is associated with longer overall survival, reinforcing the recommendations for physical activity. Research Sponsor: None.

88 Poster Session

Angiotensin receptor blockers and severe diarrhea and/or enterocolitis induced by CAPOX in patients with colorectal cancer: A multicentric cohort. First Author: Adriano Fernandes Fernandes Teixeira, Clinica AMO, Vitoria Da Conquista, Brazil Background: While patients (pts) with colorectal cancer (CRC) treated with CAPOX (capecitabine and oxaliplatin) may experience severe diarrhea, risk factors for this toxicity remain undetermined. We have previously shown that concurrent use of angiotensin receptors blockers (ARB), a known inhibitor of TGF-B which is important for gut mucosa proliferation, significantly increased the risk of severe diarrhea and/or enterocolitis. Here we conducted a larger and multicenter study to validate this finding, adjusting for other risk factors. Methods: Multicenter retrospective cohort of CRC pts who received $ 1 cycle of CAPOX. The primary endpoint was grade (G) $ 3 diarrhea and/ or enterocolitis as described by Common Terminology Criteria for Adverse Events version 5.0. Clinical data were retrieved from medical charts. Unadjusted logistic regression was used to evaluate risk factors for $ G3 diarrhea/enterocolitis (use of ARBs or angiotensin-converting enzyme inhibitors [ACEi] , age, ECOG, Age-adjusted Charlson Comorbidity Index [A-CCI], sidedness, presence of ileostomy, treatment intent [curative vs palliative] , use of proton pump inhibitors or antiacid, and center). A multivariable analysis was performed with variables with P , 0.05 deemed significant. Results: From April/2010 to December/2023, 348 pts were included: 175 (50.3%) were female, median age was 61 years (28 -87), 259 (74.4%) had stage III and 76 pts (21.9%), stage IV. 58 pts (16%) had G3 $ diarrhea/ enterocolitis, mostly before 3 rd cycle. Age $ 65 years (Odds ratio [OR] 3.18; P , 0,0001; 95% CI, 1.78 to 5.68 ); right-sided tumors (OR 1.73; P=0.075; 95% CI, 0.95 to 3.17); use of ARBs or ACEi (OR 1.57; P=0.127; 95% CI, 0.88 to 2.79); A-CCI (OR 1.12; P=0.042; 95% CI, 1.004 to 1.23) were associated with $ G3 diarrhea/ enterocolitis in univariate analyses. In the multivariable analysis, age $ 65 years was significant (OR 3.13; P=0.001; 95% CI, 1.58 to 6.20), but use of ARBs or ACEi was not significant (OR 1.16; P=0.635; 95% CI, 0.62 to 2.13). Five out of 9 pts who used Olmesartan had $ G3 diarrhea/enterocolitis. Conclusions: Among pts treated with CAPOX, $ 65 years, but not use of ARBs or ACEi, was an independent risk factor for $ G3 diarrhea/enterocolitis. Concurrent Olmesartan and CAPOX should be used with caution. Research Sponsor: None.

89 Poster Session

Oxaliplatin desensitization in patients with GI malignancies: Experience from a tertiary cancer center. First Author: Jacqueline Connell, The Christie NHS Foundation Trust, Manchester, United Kingdom Background: Oxaliplatin hypersensitivity is not uncommon in patients with gastrointestinal (GI) cancers receiving chemotherapy. The use of oral premeditations (dexamethasone, cetirizine and famotidine) starting 24 hours before treatment and continuing for a total of three days, further intravenous premedication (dexamethasone, chlorphenamine and famotidine) 30 minutes before treatment and the gradual administration of oxaliplatin over 6.5 hours in four separate escalating doses (desensitisation protocol) is commonly used in such cases. While desensitisation is an option, especially in severe cases, responses and survival outcomes upon rechallenge are not well described. Methods: A retrospective chart review of patients with various GI malignancies who received oxaliplatin-based desensitisation chemotherapy after a severe drug reaction between October 2019 and October 2022 at a single cancer centre was performed. Clinicopathological characteristics and oncological outcomes were assessed.

Results: Forty-four patients with a median age of 61 years (range 38-81) were studied.

The majority had a diagnosis of CRC (n=22; 50%), followed by oesophago-gastric (n=19; 4%), appendiceal (n=1), cholangiocarcinoma (n=1), and cancer of unknown primary (n=1). More than two thirds of patients (n=32, 73%) were treated with palliative intent.

The most common regimens associated with oxaliplatin hypersensitivity reactions after a median of 3 cycles (range 1-10) were FOLFOX (n=24, 55%), CAPOX (n=18, 41%), FLOT (n=1) and FOLFOXIRI (n=1). Seven patients (16%) had another reaction after desensitisation, leading to discontinuation of treatment. Thirty-seven patients (84%) completed treatment as planned. Treatment outcomes after desensitisation included 5 (11%) patients with no evidence of disease (NED) after adjuvant treatment, 16 (37%) patients with disease control, including 3 (7%) partial responders (PR) and 13 (30%) patients with stable disease (SD), and 23 (52%) patients with progressive disease (PD).

Conclusions: Oxaliplatin desensitisation is feasible with low discontinuation rates and leads to acceptable oncological outcomes. All patients should be offered desensitisation to allow continuation of active systemic therapy. Research Sponsor: None.

22s COLORECTAL CANCER

Real-world assessment of capecitabine and oxaliplatin (CAPOX) tolerability in patients with localized colorectal cancer undergoing curative-intent therapy: A comprehensive single institution analysis. First Author: Veronica Mears, Department of Pharmacy Services, University Hospitals Cleveland Medical Center, Cleveland, OH Background: The combination of capecitabine and oxaliplatin (CAPOX) is commonly used in patients with localized colorectal cancer (CRC) receiving curative-intent treatment. However, real-world data on the tolerability of CAPOX in this patient population are limited. This study aimed to assess the tolerability of CAPOX in a singleinstitution cohort of patients with localized CRC. Methods: A retrospective analysis was conducted using our institutional pharmacy database to identify patients with localized CRC who received neoadjuvant or adjuvant CAPOX. Demographic information, clinical characteristics, and treatment details were extracted from electronic health records. The primary endpoint was the rate of treatment completion, defined as the receipt of all planned chemotherapy cycles at full dosage, for both the overall cohort and patients aged 65 and above. Secondary outcome measures included the rate of grade 3 or higher adverse events, the frequency of hospital admissions due to CAPOX-related toxicities, and dose reductions. Results: A total of 153 patients were included in the analysis, with a median age of 61 years (range 32-84). Among them, 49% were female, 78.4% had stage III CRC, and the remaining had stage II disease. The racial distribution was 81% White and 15.7% Black. The proportion of patients who completed all planned CAPOX doses was 55.5% (85/153) in the entire cohort and 38% (23/60) in patients aged 65 and above (p = 0.22). Among patients intended to receive 4 cycles of CAPOX, only 57% (37/ 65) completed all 4 cycles. Female patients were less likely to complete treatment than male patients (p = 0.01). Dose reductions for oxaliplatin and capecitabine were observed in 37% (57/153) and 39% (59/153) of patients, respectively. Hospitalizations related to CAPOX-induced toxicities occurred in 18% (27/153) of patients, and 31% (47/153) experienced grade 3 or higher adverse events. A switch to FOLFOX was observed in 5% (8/153) of patients. Conclusions: This study highlights that a substantial number of patients with localized CRC undergoing curative-intent treatment with CAPOX do not complete the planned courses, potentially impacting their overall survival. Moreover, a significant proportion of patients experience grade 3 or higher toxicities with CAPOX, necessitating hospital admissions. These findings underscore the need for careful patient selection and management strategies to optimize the therapeutic benefits of CAPOX in this setting. Research Sponsor: None.

91 Poster Session

Comparison of the disease presentation of early-vs. later-onset colorectal cancer within the prospective ColoCare study. First Author: Zachary Gottschalk, Fred Hutchinson Cancer Research Center, Seattle, WA Background: Within the United States (US), colorectal cancer (CRC) is the third most diagnosed cancer and the second leading cause of cancer-related fatalities, with a median age at diagnosis of 66 years. While the incidence of sporadic CRC is decreasing, the incidence in those aged 18-49 years has steadily increased. Younger patients are not often screened for CRC, and they are often diagnosed at a later stage of disease. Herein, we compare the presenting symptoms and stage at diagnosis of early-onset CRC to disease in those aged 50 or greater. Methods: The ColoCare Study is a prospective cohort enrolling individuals diagnosed with primary CRC across six cancer centers in the US and one site in Germany. Serial questionnaires administered at baseline assessed demographic characteristics and symptoms experienced prior to diagnosis, while clinical data such as staging and pathology were abstracted from medical records. For this analysis, only patients who had available age and tumor stage were included. Patients diagnosed ,50 years old were categorized as "early-onset" and $50 as "lateronset." Fisher's exact test was used to compare demographics, disease state characteristics, and symptoms experienced by age group. Statistical significance was based on a two-sided alpha level of 0.05. Results: 1,996 patients were included in this analysis. Of these, 1,508 (76%) were later-onset (mean diagnosis age 64, range: 50-94), while 488 (24%) were early-onset (mean age: 42, range: 21-49). Demographic data was similar between early-and later-onset patients in terms of gender and primary site. Disease stage at diagnosis was significantly associated with age (p , 0.001). A higher proportion of early-onset patients had advanced disease at the time of diagnosis compared to later-onset for both stage III (43% vs 37%) and stage IV disease (28% vs 17%). For patients with available histologic data, younger patients were more likely to have vascular (35% vs 28%, p=0.03) and perineural invasion (33% vs 21%, p ,0.001) at diagnosis. Early-onset patients were also more likely to report symptoms prior to diagnosis (95% vs 83%, p ,0.001). Specifically, younger patients reported higher rates of abdominal pain (46% vs 23%, p , 0.001), blood in stool (71% vs 54%, p ,0.001), and changes in bowel habits (54% vs 40%, p ,0.001). General weakness and vomiting were also statistically more likely to be noted at presentation in early-onset patients.

Conclusions: In this prospective real-world cohort analysis, patients with early-onset CRC are more likely to be diagnosed with more advanced disease at presentation than later-onset patients. This analysis highlights key symptoms that should raise awareness as possible indicators of a new diagnosis of CRC, even in individuals ,50 years old. Additional disease comparisons between age groups will be presented at the meeting.

Circulating tumor DNA (ctDNA) positivity and its association with clinicopathological characteristics by novel blood-based test for colorectal cancer (CRC) screening from a multi-center large cohort: COSMOS-CRC-01. First Author: Tatsuro Murano, Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Kashiwa, Japan Background: Blood-based CRC screening has yielded performance comparable to stoolbased screening tests and may be a modality that addresses the adherence gap in CRC screening. To investigate the diagnostic performance and its clinical relevance, we evaluated the test performance of a blood-based CRC screening test in a large cohort of individuals enriched for advanced colorectal neoplasia and early CRCs. Methods: 501 individuals presenting to ten institutions in Japan from 2020 to 2021 for treatment of advanced adenomas (AAs) or CRCs were consented and provided a pre-treatment blood sample (40mL whole blood in Streck cfDNA blood collection tubes). All eligible individuals underwent surgery or endoscopic resection within 30 days after sample collection and the pathological specimens were reviewed to determine cancer histology and stage, as well as AA histology. Pre-treatment blood samples were analyzed with a multi-modal (genomic and epigenomic) cfDNA CRC detection assay (Shield, Guardant Health, USA). Final cfDNA results were correlated with clinical data to determine the association of clinicopathological characteristics with test sensitivity. This study is registered as a clinical trial under UMIN000037765. Results: 451/501 (90%) individuals met inclusion/exclusion criteria and provided adequate blood samples that passed testing quality control criteria. Median ) . Conclusions: This study evaluates the performance of a blood-based test for CRC and its clinicopathological relevance in a large-scale cohort. In this population enriched for early colorectal neoplasia, the sensitivity was 88% for CRC and 37% for AAs. This performance is consistent with previous reports. Clinical trial information: UMIN000037765. Research Sponsor: Guardant Health.

70 Poster Session

Prospective study of a multi-modal blood-based test for colorectal cancer screening. First Author: Paloma Peinado, Department of Medical Oncology, Centro Integral Oncológico Clara Campal, Hospital HM Sanchinarro, HM Hospitales, Spain/ Department of Medical Clinical Sciences, Facultad de Medicina, Universidad Camilo José Cela, Madrid, Spain Background: Colorectal cancer (CRC) screening has proven to be a useful tool for the detection and prevention of CRC. However, adherence is low despite the multiple screening options available. A blood-based CRC screening test with optimized sensitivity and specificity may improve screening adherence. We aimed to prospectively evaluate the performance of a multimodal blood-based colorectal neoplasia screening test in individuals presenting for colonoscopy. Methods: This prospective, observational study was developed in four hospitals in Spain and enrolled individuals (45 -84 years of age) undergoing colonoscopy, including diagnostic and screening colonoscopies, between March 2020 and September 2021. Eligible individuals consented to use of medical records for research and to provide a blood sample prior to colonoscopy procedure. Individuals were followed for one year. Whole blood was collected and shipped ambient to a central laboratory for analysis (Shield, Guardant Health, Redwood City, CA, USA). The blood-based colorectal neoplasia test is a 500kb next-generation sequencing based panel and bioinformatic platform that incorporates cell-free DNA (cfDNA) methylation-based partitioning to identify cancer related genomic alterations and epigenomic modifications (methylation and modifications in chromatin state). Results are integrated to yield a binary "positive" or "negative" result. Here we present findings correlating the blood-based test results with colonoscopy findings and findings from available 1-year follow-up data. Results: 556 out of 598 eligible individuals had an evaluable colonoscopy and a blood-based test result that passed quality control standards. Of the 556 individuals, 52% were female; median age was 55 years (21% age 45 -49, 74% age 50 -74, 4% age 75+). Reasons for colonoscopy were symptoms (49%), average risk screening (33%), positive stool-based test (6%), positive family history (11%) or other reasons (1%). Colorectal adenocarcinoma prevalence rate was 1.4%. Sensitivity for CRC detection was 100% (8/8; Stage I, 1; Stage II, 3; Stage III, 2; Stage IV, 2). Sensitivity for advanced adenoma (AA) detection was 22%. Specificity for advanced neoplasia (CRC + AA) was 91%. Negative predictive value (NPV) for CRC detection was 100% and positive predictive value (PPV) was 13%. 1-year follow-up data was available for 504 individuals, of whom 9 patients developed cancer (none CRC), of whom 1 had an initial positive Shield result. Conclusions: In this prospective study of individuals eligible for colonoscopy, sensitivity and specificity of the blood-based test showed a performance consistent with the available stool-based non-invasive screening options. This, combined with a more acceptable mode of testing suggests that this blood-based test may be a viable CRC screening option. Research Sponsor: Guardant Health.

71 Poster Session

Colorectal Cancer Alliance: Promoting prevention and early detection with screening navigation and a personalized recommendation via a digital screening quiz tool for colorectal cancer. First Author: Kim Newcomer, Colo-Colorectal Cancer Alliance, Washington, DC Background: Evaluating the effectiveness of a Colorectal Cancer screening navigation model delivered in a digital platform offered by a patient advocacy organization. Designed as a digital screening quiz tool and live navigation to promote CRC screening, the Colorectal Cancer Alliance's Screening Quiz is a risk stratification tool that connects respondents to live certified cancer care navigators delivering evidence-based interventions to increase CRC screening, education and patient and family support. The framework utilizes small and mass media, one-on-one education and patient navigation services to help address and reduce barriers to care. Critical interventions which research shows that on-time screening for CRC leads to better outcomes. Methods: The Screening Quiz has been promoted through social sharing, community outreach, media, including influencer campaigns to increase outreach to at-risk communities. Questions assess personal and family history, hereditary syndromes, and demographics to provide a CRC screening recommendation based on current USPSTF guidelines. Respondents overdue for screening who opt in, are triaged to the Alliance's patient navigation team for follow-up. This interaction includes phone calls and emails for symptomatic individuals or at high risk for CRC, telephonic and email for average-risk uninsured, and emails for average-risk insured. At-risk individuals are connected to resources, such as financial assistance, free at-home screening tests, and colonoscopy scheduling services. Results: July 2022 to August 2023, the Screening Quiz provided over 30,000 screening recommendations. The median age of respondents was 48; 33% of the respondents were between the ages of 45 to 64. Of the respondents, 29% were male and 71% were female. Most were White (74.3%), but nearly half of those who opted into navigation identified as BIPOC, including 14.4% Black/AA, 17.8% Hispanic or Latino, 7.7% Asian, and 2.5% AI/AN. Most respondents were symptomatic (65.5%) but 7.3% were asymptomatic high-risk. These two groups represented 88% of 1,851 respondents triaged to patient navigation. Conclusions: This digital screening tool and live navigation framework may serve as a key solution in driving CRC screening compared to other interventions. Providing access to live navigation, educational resources, and support services for CRC screening and diagnosis.The Alliance is uniquely positioned with its national network of volunteers, partners, and community presence to effectively reach at-risk communities. Aligning with the science of evidencebased interventions, the Alliance will continue to leverage the Screening Quiz in partnership with healthcare and community stakeholders to close Colorectal Cancer screening gaps. Research Sponsor: None.

73 Poster Session

Comprehensive analysis of differentially methylated regions in colorectal cancer (CRC). First Author: Omid Solari, Natera, Inc., San Carlos, CA Background: Epigenetic alterations have been shown to govern many disease states, including cancer. A key epigenetic mark is the DNA methylation of CpGs. Large studies, like The Cancer Genome Atlas, have shown that DNA methylation can differentiate between cancer status and type. Here, differentially methylated genomic patterns were defined between patients with CRC and healthy individuals by utilizing patterns of comethylation of adjacent CpG loci. Methods: Deep, whole genome bisulfite sequencing (WGBS) was conducted on DNA samples from 100 healthy individuals (median effective coverage of 352x638x) and from 75 patients with CRC (median effective coverage of 48x618x). The two cohorts were chosen to be balanced in terms of age (CRC: 58611 years; healthy: 5768 years) and to represent major ethnicities in the USA, and the CRC cohort was chosen to represent all stages, histologies and morphologies, and microsatellite instability (MSI, 23%). A novel machine learning model was developed to discover differentially methylated regions between the healthy and CRC cohorts as well as between subpopulations within the CRC cohort, including age, sex, stage, histology, and MSI vs microsatellite stability (MSS). Results: In total, we discovered 132,911 differentially methylated regions between healthy and CRC cohorts, spanning more than 1.14 million CpGs. 76% of all discovered regions were hypermethylated (70% CpG islands, 1.3% CpG shelves, 21% CpG shores) and the rest were hypomethylated (7.3% CpG islands, 8.6% CpG shelves, 25% CpG shores). We also discovered 220 hypermethylated regions that were differentially methylated between CRC MSI samples and CRC MSS samples and healthy cfDNA samples. Furthermore, we discovered subtype-specific differentially methylated regions, such as 62 hyper-methylated regions that were differentially methylated between mucinous adenocarcinoma samples and the rest of the cohort. Conclusions: Based on deep WGBS data from heterogeneous cohorts, representative of the US population eligible for CRC screening, we identified many differentially methylated regions as strong biomarker candidates for the early detection of cancer. Compared to recurrently mutated driver genes in CRC, we find that differential methylation profiles of CRC samples are generally much more homogenous and are therefore ideal biomarkers for targeted sequencing panels with the purpose of early cancer detection. Further, analysis of these patterns based on clinicopathologic factors enabled discovery of subtype specific markers, which can be incorporated to ensure equivalent performance for underrepresented subtypes or subpopulations. Research Sponsor: None.

Clinicopathologic characteristics of patients with early-onset colorectal cancer. First Author: Maki Takagi, Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan Background: Although the incidence of colorectal cancer has been declining in the United States in recent years, the incidence of young patients under 50 years of age has been reported to be increasing by several percent per year. Various studies have been conducted to characterize early-onset colorectal cancer (EO-CRC); however, it has been unclear whether it is a different entity from late-onset colorectal cancer (LO-CRC). In this study, we evaluated the clinicopathologic characteristics of EO-CRC in Japan.

Methods: This study included 1,336 patients who underwent surgical resection for colorectal cancer at Tokyo Metropolitan Komagome Hospital from January 2015 to December 2019. We performed genetic testing for patients with suspected Lynch syndrome after providing genetic counseling and obtaining informed consent. The study protocol was approved by the Institutional Review Board. Results: Of the 1,336 colorectal cancer patients, 117 (8.9%) had EO-CRC with a median age at the diagnosis of 44 (17-49) years. Tumors were located at right-sided colon in 23 patients and left-sided colorectum in 92 patients with EO-CRC, respectively. The clinical stage of the tumor was I in 19, II in 23, III in 50, and IV in 23 patients with EO-CRC, respectively. Histologically, differentiated type, undifferentiated type, and mucinous carcinoma were 106, 5, and 3 patients, respectively. KRAS mutation was detected in 25.0% and BRAF V600E was detected in 4.3% of patients with EO-CRC. In the microsatellite status, MSI-High was detected in 6 (5.1%) patients with EO-CRC, of whom 3 (2.6%) were diagnosed with Lynch syndrome by genetic testing. Causative genes were MLH1 in 2 patients and MSH2 in one patient. In hereditary tumors, 2 patients with familial adenomatous polyposis were included in addition to Lynch syndrome. On the other hand, 1,219 (91.2%) had LO-CRC with 34.5% of KRAS mutation and 6.4% of BRAFV600E. MSI-High was detected in 69(5.7%) patients with LO-CRC，of whom 5 (0.4%) were diagnosed with Lynch syndrome. Lynch syndrome was significantly more common in EO-CRC (p=0.026).

Conclusions: The alterations of KRAS and BRAF tended to be more frequent in EO-CRC. The frequency of hereditary CRC was more frequent in EO-CRC than in LO-CRC. Research Sponsor: None.

75 Poster Session

Genetic testing of Japanese patients with serrated polyposis syndrome: A multicentric study. First Author: Akinari Takao, Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan Background: Serrated polyposis syndrome (SPS) is a rare condition associated with an increased risk of colorectal cancer. Previous studies have identified germline truncating variants of the RNF43; however, patients harboring these variants comprise a small part of those with SPS, in most of whom the causative gene remains unknown. To date, no study has described the genetic features of Japanese patients with SPS. The present study aimed to identify candidate causative genes of SPS in Japanese patients.

Methods: Captures for equal to or more than 55 gene regions were performed using Agilent HaloPlex or Ion AmpliSeq technologies in SPS patients enrolled in The Study Group for Establishment of Diagnosis of Hereditary Gastrointestinal Tract Cancer Syndromes Based on a Next-Generation Sequencing Technology (SGHGCS). Whole exome sequencing of tumor tissue was performed whenever a candidate gene was identified. Results: Eleven patients (four males, seven females) were enrolled. Of these, nine had a history of colorectal cancer; four had a family history of colorectal cancer; and two had a family history of polyposis. Genetic testing identified two variants of VUS, POLD1 c.670C.T (p.R224C) and BRCA2 c.4169T.G (p.L1390W). Additionally, a nonsense variant, BUB1:c.1543G.T p.Gly515Ter was deemed likely to be pathogenic.

The patient with the BUB1 variant was 47-year-old female with transverse colon cancer with more than 50 serrated polyps. She was a non-smoker. The variants detected in the transverse colon cancer did not include the canonical variants in common colorectal cancer, such as APC, KRAS or TP53 and were mostly transition substitutions (C.T).

Conclusions: BUB1 was identified as a novel candidate causative gene of SPS in a patient with SPS with no smoking habit. These findings will hopefully contribute to our understanding of the genetic basis of SPS. Research Sponsor: None.

76 Poster Session

One of these is not like the others: A descriptive study of the attenuated phenotype of PMS2. First Author: Edward D. Esplin, Invitae, San Francisco, CA Background: Data from Lynch syndrome (LS) registries reveal that patients (pts) with PMS2 pathogenic germline variants (PGVs) have the lowest cancer risk. This retrospective study of pts undergoing germline genetic testing (GGT) for any indication compared the phenotypes of PMS2 carriers to other LS pts. We hypothesized that PMS2 pts were more likely to have no cancer or non-LS associated cancers than other LS pts.

Methods: All Pts with a single PGV in any LS gene were identified from a commercial laboratory database. Demographics and personal and family cancer history data were clinician-reported on the test requisition form. Data from PMS2 pts were compared to MSH6 and MLH1/MSH2/EPCAM pts using descriptive statistics, unpaired two-samples t tests, Chi-square tests, and multivariate logistic regression analyses that also included patients with no PGVs, with p,0.05 defining significance. Results: 17,711 pts met inclusion criteria (5,189 PMS2, 5,182 MSH6, and 7,340 MLH1/MSH2/EPCAM). PMS2 pts were significantly older at testing (mean 55.1616.0y) than MLH1/MSH2/EPCAM (48.7615.7y) and had significantly less family cancer history (84.9%) than both MSH6 (86.8%) and MLH1/MSH2/EPCAM (86.6%) pts. PMS2 pts had lower odds of any colorectal and uterine cancers than the MSH6 and MLH1/MSH2/EPCAM cohorts (Table ). All LS-related PGVs were significantly associated with lower odds of breast, pancreatic, and prostate cancer. Conclusions: Pts with PMS2 PGVs were older at the time of testing and had lower odds of any and LS-related cancers than other LS pts. These data are consistent with prior registry studies and can aid in counseling and management of PMS2 pts. Research Sponsor: None.

Results of multivariate logistic regression analyses; each adjusted for sex, age, family history, ethnicity, and number of genes analyzed. Multiple testing correction for p-value and CI based on number of outcomes (10) and genes (3) with a = 0.004. Background: LS is among the most common cancer (CA) syndromes affecting 1:280 individuals and portends high lifetime CA risk. Clinical trials are currently evaluating whether frameshift peptide vaccination (FSPVAX) could reduce LS CA risk. FSPVAX enhances immune response to diverse FSP neoantigens in MSI-H tumors and has shown promising results in an MSH2-mutant mouse model and metastatic MSI-H CRC. However, negative public attitudes towards vaccination and evidence suggesting low uptake of ASA chemoprevention (CP) among patients with LS could undermine success of this novel therapy. Here, we benchmark attitudes towards FSPVAX for CA prevention against colonoscopy (COLO) and aspirin or NSAID chemoprevention (CP).

Cancer

Methods: The PREVENTLynchII survey (IRB 20-8014) was distributed electronically to 1) participants in the Fox Chase Cancer Center (FCCC) Risk Registry and 2) members of two online LS support groups. Patients were invited to complete the one-time survey after providing informed consent. Demographic and personal CA history were collected. Attitudes were measured on 9-point scales indicating low vs high agreement with belief statements: e.g. "Colonoscopy is a convenient way to lower my risk of LS-related CA." Results: Overall 296 participants at FCCC, nationally, and internationally completed the survey. Median age was 52.6 years , 84% female, and 95% White. Affected genes included MLH1 (20.3%), MSH2/EPCAM (35.5%), MSH6 (28.7%), and PMS2 (15.5%). Use of CP was uncommon (32.1% and 5.1% respectively). Stratified analyses of COLO perceptions by sex, age, and personal history of CA showed no differences. Interestingly, US pts viewed ASA as more convenient than non-US, and with lower risk of side effects (p=0.007), but were no more likely to use or recommend CP. Compared to COLO, FSPVAX was overall viewed as more convenient, but side effect concerns were higher, and perceptions of efficacy were lower (all p,0.001), while compared to CP, FSPVAX was less convenient and fostered greater concerns about side effects, but was viewed as having higher potential preventive efficacy (all p,0.001). FSPVAX perceptions showed high variability: pts .50 (p=0.003) and CA pts (p=0.01) saw FSP as more convenient (p=0.003) than younger and unaffected pts. CA pts reported higher reassurance than unaffected (p=0.04), while those .50 were more likely to participate in an FSPVAX study (p=0.04). US pts perceived more side effect risk of FSPVAX than non-US (p=0.003).

Conclusions: Concerns about ASA CP and FSPVAX convenience, side effects, and efficacy are common among US and international patients with LS. Research Sponsor: None. Impact of revising colorectal cancer screening guidelines on health care resources in Canada. First Author: Brendan Chia, BCCA, Vancouver Cancer Centre, Vancouver, BC, Canada

Background: The rising incidence of early-onset colorectal cancer (CRC) has prompted U.S. organizations to lower the recommended CRC screening age for average risk adults from 50 to 45 years old, while Canadian programs remain unchanged. Canadian guidelines also differ from the U.S. in preferentially screening with a fecal immunochemical test (FIT) and recommending against colonoscopies as a screening test. Differences in national healthcare administration warrants investigation into the resource impact of updating screening guidance in Canada. Methods: Microsimulation modeling was performed using OncoSim (version 3.6) to project health and economic outcomes of different CRC screening strategies based on Canadian population data. Four simulated birth cohorts of the Canadian population born between 1973-1992 were tracked for a 40-year span from the year the oldest in each cohort turned 40 until the youngest in the same cohort turned 75. Colorectal adenoma rates were adjusted according to cohort risk ratios estimated from historical incidence data to reflect real-world CRC rates. Outcomes were reported for the cumulative cohort.

79 Poster Session

Clinicopathological features of post-colonoscopy colorectal cancer in patients with Japanese Lynch syndrome: A multicentric retrospective observational study. First Author: Akinari Takao, Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan Background: Due to the high incidence of heterochronic and concurrent colorectal cancer in Lynch syndrome (LS), colonoscopic surveillance is recommended in Japan every 1-2 years. Even with regular colonoscopic surveillance, post-colonoscopy colorectal cancer (PCCRC) often occurs in the intervals between surveillance, but there are currently no reports of the details of PCCRC in LS in Japan. Methods: Of 1756 colonoscopies performed between 2009 and 2018 in 316 patients with a diagnosis of LS confirmed by genetic testing who were enrolled in a nationwide, Japanese, multicentric study conducted by the Committee of Hereditary Colorectal Cancer of the Japanese Society for Cancer and Rectum, 1203 colonoscopies in 256 patients were assessed to determine the clinicopathological characteristics of PCCRC, after including cases of first-time surveillance, previously untreated lesions, and inadequate pretreatment. Then, the incidence of PCCRC was compared between patients with a median surveillance colonoscopy interval , 12 months (group A) and . 12 months (group B).

Results: There were 49 cases of PCCRC with a total of 84 lesions. The number of lesions per tumor depth was 66, one, five, seven, four, and one for pTis, pT1, pT1a, pT1b, pT2, and pT3, respectively. Two (2.4%), 20 (23.8%), 21 (25%), four (4.8%), 18 (21.4%), and 19 (22.6%) lesions were localized in the cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum, respectively. In pTis-pT1b, the macroscopic type was 0-IIa in 33 lesions (41.8%), 0-IIc in four lesions (5.1%), 0-IIa+IIc in five lesions (6.3%), 0-IIb in one lesion (1.3%), 0-Is in 15 lesions (19%), 0-Ip in one lesion (1.3%), 0-Isp in 16 lesions (20.3%), and unknown in four lesions. In pT1b-pT3, seven lesions (63.6%) were smaller than 20 mm. In terms of the median interval between surveillance colonoscopies, 130 patients had a median interval , 12 months (group A), and 126 patients had a median interval . 12 months (group B). In groups A and B, PCCRC, metachronous cases, simultaneous cases, and depths than pT1b were observed in 29 (22%) and 20 (16%) cases (p=0.21); 14 (11%) and two (1.6%) cases (p=0.006); six (4.6%) and one (0.8%) case (p=0.22), and six (4.6%) and four (3.2%) cases (p=1), respectively. Conclusions: In PCCRC in Lynch syndrome, invasive carcinomas , 2 cm should be noted. In addition, a surveillance interval of 12 months may be insufficient in patients with LS. Thus, further investigation is warranted. Research Sponsor: None.

80 Poster Session

Impact of the COVID-19 pandemic on colorectal cancer stage at presentation. First Author: Malcolm Hart Squires, Atrium Health, Levine Cancer Institute, Charlotte, NC Background: The primary study objective was to assess the impact of COVID-19 on the stage at presentation for patients with newly diagnosed colorectal cancer treated within a large cancer center network. Additionally, we aimed to evaluate differences in pathologic stage and treatment modality for patients diagnosed with colorectal cancer both immediately before and during the height of the COVID-19 pandemic. Methods: A retrospective analysis was performed on all subjects newly diagnosed with colorectal cancer between January 2019 and April 2021 at Levine Cancer Institute. Patients had a primary diagnosis of adenocarcinoma of the colon, rectum, or appendix. Patients were categorized into two cohorts based on date of diagnosis, with the pre-COVID-19 group diagnosed between January 2019 and February 2020 and the COVID-19 group diagnosed between March 2020 and April 2021. Chi-squared tests were used to evaluate the association between COVID-19 group and stage at presentation as well as pathologic stage. Results: A total of 1,190 patients were diagnosed with colorectal cancer within the study timeframe.

Of the 613 patients diagnosed pre-COVID-19, 159 (25.9%) had metastatic disease at initial presentation. Comparatively, 577 patients were diagnosed during the COVID-19 study period, with 143 (24.8%) presenting with metastatic disease (p = 0.65).Of the 888 patients who presented with non-metastatic disease, 770 underwent primary surgical intervention for the initial treatment of their cancer, with 396 (87.2%) pre-COVID-19 and 374 (86.2%) COVID-19 patients receiving surgery (p = 0.65). Likewise, no significant difference was observed for T-classification, N-classification, or overall pathologic stage among patients undergoing surgical resection between the pre-COVID-19 and COVID-19 groups (p = 0.20; Table ). Furthermore, amongst patients who presented with non-metastatic disease, chemotherapy was utilized for 200 (44.1%) patients diagnosed pre-COVID-19 and 190 (43.8%) patients diagnosed during COVID-19 (p = 0.93). Conclusions: We did not observe a significant difference in the proportion of patients presenting with metastatic colorectal cancer during COVID-19 versus those presenting pre-COVID-19. Furthermore, there was no significant difference observed among non-metastatic patients between the two groups for rates of initial surgical resection, pathologic stage, and treatment with chemotherapy.

81 Poster Session

Alteration of metabolic syndrome and the risk of colorectal cancer in individuals younger than 50 years. First Author: Eun Hyo Jin, Seoul National University Hospital, Songpa-Gu, South Korea Background: Colorectal cancer (CRC) is a significant global health concern, with a rising incidence of early-onset cases in individuals under 50. This trend may be influenced by various factors, including metabolic syndrome (MetS), obesity, dietary habits, and lifestyle choices. However, the impact of changing MetS status on the risk of early-onset CRC remains understudied. Methods: A total of 3,340,635 Korean national insurance beneficiaries that received two consecutive biennial mandatory health exams (2009) (2010) (2011) were followed-up until 2019. Participants were categorized into MetS-free, recovered, developed, or persistent groups. The study assessed CRC risk patterns associated with these MetS dynamics, considering factors like age, sex, smoking, alcohol consumption, exercise, and income status. Results: Among 20-39-year-olds, those with persistent MetS had a 16% higher risk of CRC (adjusted hazard ratio [aHR] 1.16; 95% CI, 1.00-1.33) compared to MetS-free individuals. Furthermore, persistent MetS was associated with a 29% higher risk of rectal cancer in this age group, while recovery from MetS also increased rectal cancer risk by 28%. Among 40-49-year-olds, the MetS-persistent group had a 22% higher risk of CRC (aHR 1.22; 95% CI, 1.14-1.30), with a 34% higher risk of distal colon cancer, while those who developed MetS showed a 26% higher risk of CRC compared to the MetS-free group. Conclusions: This study highlights that the persistence of MetS in young adults is associated with an increased risk of early-onset CRC. The findings suggest that managing MetS in young individuals through lifestyle modifications, such as weight reduction and regular exercise, could be beneficial in reducing the risk of early-onset CRC. Research Sponsor: None.

20s COLORECTAL CANCER

COLONTOWN Searching Safari: Education to remove barriers to pursue clinical trials for patients with metastatic colorectal cancer (mCRC). First Author: Julie Clauer, Paltown/Colontown, Burbank, CA Background: Clinical trials can expand otherwise limited treatment options for patients with metastatic cancer. Yet, the complexity of the trial landscape can prevent patients from pursuing trials. Even in mCRC patients motivated to participate in trials, 79% described trial search negatively, mainly 'overwhelming.' We hypothesized that "clinical trial-literacy" and familiarity with the tools/process of pursuing trials were critical precursors for patients to incorporate trials into their treatment plan. To test this, we, as managers of COLONTOWN, a large, online CRC patient/caregiver community, developed an interactive course. Methods: We reviewed many posts from the COLONTOWN clinical trial groups to identify gaps between the desire to participate in a trial and the knowledge/tools needed to do so. We then determined those most likely to benefit as mCRC MSS patients interested in, but not in urgent need of, trials. We developed a 4-week long course with 5 hours of live online sessions and 5 hours of homework. Participants built fluency in the language of clinical trials, learned about available tools, and identified and assessed trials in the context of their personal needs and disease dynamics. Unlike most other trial resources, the focus was on informed patient-centered decision-making, not on the science or mechanics of trials. The course was offered 3 times in 2022/23 with iterative improvements after each session. Participants (n=48) were assessed for their attitudes around trials before and after the course to measure impact. Results: We found that our repeatable, scalable course improves mCRC patient perceptions of and skills to pursue trials as evidenced by pre-course vs. post-course surveys. This included average response to "How prepared do you feel to find a clinical trial?" increasing from 2.1 to 3.8 on a 5-pt scale and positive sentiment about the process rising from 7% to 71% (table ). Positive feedback on meeting course objectives and amount of coursework being 'just right' (96% and 92% of responses, respectively) support the material's value for time invested. Conclusions: Through systematic skill building, self reflection, and practical tools, our guided course can build confidence and empower patients and caregivers to take the next step to pursue clinical trials. Patient education can indeed help overcome oftenoverlooked emotional and knowledge barriers to pursuing clinical trials present even in a motivated patient population. Next, we plan to create and assess the benefit of an additional ondemand e-learning course and to expand to other patient groups. Research Sponsor: None.

83 Poster Session

Real-world adoption of 3 months of adjuvant oxaliplatin chemotherapy in patients with stage III colorectal cancer (CRC). First Author: Tharani Krishnan, BC Cancer -Vancouver, Vancouver, BC, Canada

Background: Based on the IDEA analysis, 3 months (mos) of adjuvant chemotherapy (ACT) with CAPOX has emerged as an option for both low-risk and high-risk stage III CRC. This has resource utilization, cost and toxicity benefits (particularly less neurotoxicity) without compromising efficacy. This study examines the patterns of uptake of CAPOX vs FOLFOX and duration of ACT in a contemporary post-COVID real-world cohort of patients (pts) in the province of British Columbia (BC), Canada. Methods: The provincial pharmacy database was used to identify pts with resected stage III CRC who received adjuvant CAPOX or FOLFOX between January 2021 and December 2022. Pts with rectal cancer requiring neoadjuvant chemotherapy or radiotherapy were excluded. Demographic, tumor, and treatment information was collected. "High-risk features" were defined as pT4 or pN2 tumors. "Urban" setting was defined based on the population size of the regional health authority. Descriptive statistical analyses were performed to examine baseline characteristics and Fisher's exact test was used to examine univariate associations. Results: 452 pts were included, of which 234 (52%) and 218 (48%) were planned to receive 3 and 6 mos of ACT respectively (see table

84 Poster Session

Local excision to enhance organ preservation in rectal cancer after favorable response to total neoadjuvant therapy. First Author: Aron Bercz, Memorial Sloan Kettering Cancer Center, New York, NY

Background: Total neoadjuvant therapy (TNT) for rectal cancer (RC) can achieve clinical complete response (cCR) and organ preservation in as many as 45% of patients, with watch-and-wait (WW) management. For tumors that persist or regrow after TNT, standard management is total mesorectal excision (TME), which can result in poor bowel function or permanent colostomy. In certain cases, only residual adenoma or mucosal based carcinoma may remain after TNT. Local excision (LE) is a minimally invasive surgical alternative that preserves the rectum. Here we evaluate case selection, safety, and efficacy of LE for small tumors that persist or regrow after TNT. Methods: Our retrospective review identified 72 RC patients from August 2010 -July 2023 who underwent LE for tumors that either remained after TNT or achieved cCR and later regrew. Median follow up from end of TNT was 3.2 years. LE was selectively offered if the tumor was suspected to arise from an adenoma or a small cancer confined to mucosa, based on clinical impression and biopsy. Collected data included tumor characteristics and pathology, surgical complications, length of stay (LOS), local and distant tumor recurrence, and organ preservation. Results: Pretreatment MRI staging was 5% T1, 23% T2, 68% T3, and 4% T4. Median distance from anal verge was 4.8 cm. 90-day complications after LE included dehiscence (6%), rectal pain (5%), transient urinary retention (4%), bleeding (4%), and minor incontinence (4%). One patient developed pelvic sepsis requiring drainage of perirectal abscess and fecal diversion. Median LOS was 1 day (range 0-4). Pathologic review demonstrated invasive cancer in 27 LE specimens, while 45 had either benign pathology or carcinoma in situ (table 1 ). R1 pathology was present in 8 of 27 (30%) invasive cancer specimens. 6 of 27 (22%) patients with invasive cancer (3 ypT1, 3 ypT2) subsequently underwent TME. 3 of 27 patients (11%) developed distant metastases. Of the 45 patients with benign LE pathology, 3 (7%) later required TME for subsequent cancer regrowth (range 4-22 months after LE). 4 of 45 patients (8%) developed distant metastases. Overall organ preservation rate following LE was 87.5%, with median follow-up of 2.4 years after surgery. For all 9 LE patients who ultimately underwent TME, there were no pelvic recurrences and one distant recurrence. Conclusions: Small, mucosal based tumors that contain minimal or no invasive cancer are common findings after TNT. For appropriately selected patients, LE is a safe and effective initial option, given high observed rates of local control and organ preservation, with low surgical morbidity. If more advanced disease is encountered on final pathology, TME should be considered. These data support the use of LE as an important adjunct to WW management.

85 Poster Session

The impact of multidisciplinary care for locally advanced rectal cancer referrals: A systems perspective. First Author: Victor Lo, University of Ottawa, Ottawa, ON, Canada Background: Locally advanced rectal cancer patients require multidisciplinary care for treatment planning. We sought to determine whether the order of surgical and radiation oncology consultation in relation to medical oncology consultation affects the time from cancer diagnosis to treatment initiation and the requirement for additional pre-treatment visits with medical oncology. Methods: We conducted a retrospective chart review of adult patients referred to The Ottawa Hospital with locally advanced rectal adenocarcinoma, seen in consultation by a surgical, radiation, and medical oncologist between January 2018 and December 2022. Results: Of 195 patients, the median time from diagnosis to treatment was 55 days . Both surgical and radiation oncology consultation preceded medical oncology consultation in a minority of patients (72; 37%), and 48 (25%) patients required multidisciplinary cancer conference (MCC) discussion. However, the time from cancer diagnosis to treatment initiation was not significantly different between patients who were and were not seen by the surgeon and radiation oncologist prior to the medical oncologist (56 vs. 55 days respectively), nor if MCC discussions were or were not required (55 vs. 55 days). However, almost half of all patients (93; 48%) required an additional pre-treatment visit with their medical oncologist, and patients who saw both surgical and radiation oncology prior were significantly less likely to require additional pre-treatment visits with medical oncology (25% vs. 61%; p,0.0001). Conclusions: The time from cancer diagnosis to treatment initiation was not significantly impacted by the order of specialist consultations with the multidisciplinary team, nor if patients required MCC discussion or additional pre-treatment visits with medical oncology. However additional pre-treatment visits with medical oncology were significantly more likely to occur when patients were seen by medical oncology prior to surgical and/or radiation oncology, representing a logistical and financial inefficiency in the system, and a potential area for process improvement. Research Sponsor: None. Retrospective review of compliance with guideline-directed germline testing in microsatellite instability-high colorectal cancer treated at the Veterans Health Administration. First Author: Karly Williams Silva, University of Washington, Seattle, WA Background: Lynch syndrome (LS) is an autosomal dominant inherited cancer syndrome that confers an increased risk of colorectal cancer (CRC). As clinical and history features under-recognize LS cases (3-5% of CRC), universal screening of CRCs for LS is recommended. Patients whose CRCs are mismatch repair protein deficient (dMMR) and/ or microsatellite instability high (MSI-H) are recommended to have subsequent genetics evaluation to screen for germline mutations. Confirmed LS changes cancer surveillance recommendations for affected patients and their relatives. Within Veterans Health Administration (VHA), GT is ordered by genetic counselors at genomic medicine telehealth centers (GMTC), after initial consultation. We aim to quantify rates at which CRC patients treated at the VHA complete germline testing (GT) when indicated. Methods: The electronic health records (EHRs) of VHA patients with known dMMR/MSI-H CRC were reviewed. Cases were extracted from both Veterans Affairs (VA) Puget Sound and referral VA MSI testing laboratories. Surgical pathology reports and clinical documentation were reviewed in Joint Longitudinal Viewer (JLV) to determine if GT was indicated and reason for non-testing, if not performed. Patients with known LS prior to development of CRC were excluded, and patients with dMMR in MLH1 or MSI-H with concurrent BRAFV600 mutation and/or MLH1 hypermethylation were considered to have sporadic CRC. Results: Of 110 patients with abnormal tumor LS screening; 39 (36%) patients' tumor tissue underwent IHC for dMMR, 16 (14%) underwent PCR for MSI, and 55 (50%) had both. 45 (41%) patients were classified as somatic MSI-H. 65 (59%) patients met criteria for referral for GMTC and GT. Of these 65, 49 ultimately did not undergo GT and 16 did, which confirmed 4 cases of LS and revealed 1 variant of uncertain significance in the MLH1 gene. Reasons for non-testing were: 7 (14%) declined all cancer testing and treatment after CRC diagnosis or were lost to follow-up/declined establishment of cancer care, 3 (6%) declined referral to GMTC, 14 (29%) accepted referral to GMTC but never had consultation, 7 (14%) accepted referral to GMTC but declined GT when offered, and 18 (37%) were never offered GMTC referral or GT.

Conclusions: A majority of dMMR/MSI-H cases with an indication for GT were referred for genetic counseling, but only a small subset completed testing. This analysis identified multiple areas for improvement, including a lack of recognition by providers for the need for GT, and lack of completion of testing by patients at multiple levels. Further evaluation of VHA-specific barriers is needed to improve the quality of delivered care.

Research Sponsor: None. Poster Session

Associations of postdiagnosis changes in physical activity with all-cause mortality among patients with stage I-IIA colorectal cancer. First Author: Karel Smit, Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands

Background: Several observational studies show an association between physical activity (PA) at diagnosis and reduced risk of mortality among colorectal cancer (CRC) patients, but there has been limited research examining the potential benefit of changes in PA levels after CRC diagnosis. Here we investigate the association between change of PA and all-cause mortality in patients with stage I-IIA CRC receiving resection with curative intent. Methods: Data were used from two large Dutch CRC cohort studies (PLCRC & COLON), which assessed PA at diagnosis (T0), six (T6) and twelve (T12) months after diagnosis, using the SQUASH questionnaire. A total of 2540 stage I-IIA CRC patients with repeated PA measures (i.e. a T0 and at least a T6 or T12 questionnaire) were used for this analysis. Total PA was quantified by calculating Metabolic Equivalent Task (MET) hours per week and categorized as low, moderate, and high PA, based on tertiles of an age-and sex-matched sample of the general population. PA changes were evaluated at T6 and T12 relative to T0. Being active was defined per timepoint as being in the moderate or high total PA group, or adhering to the PA guideline (minimum of 150 minutes per week of moderate-intensity PA). Cox proportional hazards models were used to study the association between PA variables and all-cause mortality, adjusted for age, sex, BMI, and tumor location (colon vs rectum). Results: Median follow-up time was 35 months (interquartile range 19 -55) during which a total of 133 deaths occurred. Being active at both T0 and T6 compared to being inactive at these timepoints, was associated with a lower rate of all-cause mortality for both PA variables (adjusted hazard ratio (HR) 0.39 [95% confidence interval 0.24-0.63] and 0.41 [0.23-0.72] for total PA and guideline adherence, respectively). Similar results were found when comparing T12 to T0 (being active according to total PA HR 0.20 [0.09-0.42] and guideline adherence HR 0.31 [0.14-0.72]).

Analytical Limit of Detection (LoD) was estimated using ~5,000 in silico dilution samples generated from blood samples from 25 CRCs and ~1,650 non-ACNs. Results: This training approach yielded a 2X improvement in the analytical LoD95 (0.004% vs 0.008%) compared to the original model validated in the ECLIPSE trial. The model also yielded an increase in overall CRC clinical sensitivity from 84% to 91%, N=45, with notable sensitivity improvement from 76% to 88% in detecting early localized stage I/II CRC, N = 25, while maintaining specificity at 91%. Conclusions: This enhanced cfDNA-based CRC screening blood test shows improved performance in early stage CRC detection demonstrating the potential of continuous improvement in the performance of cfDNA-based screening tests powered by data and clinical insights. Research Sponsor: Guardant Health.

92 Poster Session

A single-institution experience of acute toxicities in patients treated with short course hypofractionated radiotherapy in locally advanced rectal cancer. First Author: Katie Nadine Lee, Harvard Radiation Oncology Program, Boston, MA Background: Hypofractionated short course radiation treatment (SCRT) as part of a total neoadjuvant treatment (TNT) approach to treat rectal cancer has increased in popularity since the publication of the RAPIDO trial. However, the literature on SCRT for rectal cancer has not reported significant acute toxicities in the weeks immediately following the completion of treatment. This study examines the acute toxicities in patients treated with hypofractionated radiation therapy as part of their definitive treatment for rectal cancer. Methods: At our institution, we retrospectively analyzed 71 patients with locally advanced rectal cancer treated between 2016-2022 with SCRT (25 Gy in 5 fractions) as part of definitive treatment. Acute toxicity caused by radiation was defined as that occurring from the start of radiation treatment to either 30 days post radiation completion, the start of chemotherapy, or date of surgery, whichever occurred first. Acute neuropathic lumbosacral (LSN) pain was defined as bilateral radiating pain down the lower extremities.

Matched patients without reported LSN pain were identified and matched on N stage, location of tumor, and treatment position. Organs at risk were contoured on the CT planning scan and dosimetric analysis was conducted on the patient's treatment plan.

Results: In 71 patients treated with SCRT, we identified diarrhea (n=34, 47.9%), rectal pain (n=15, 21.1%), rectal urgency (n=15, 21.1%) nausea (n=14, 19.7%), and rectal bleeding (n=12, 16.9%) as frequent acute toxicities in the setting of SCRT. For patients with rectal pain, 31.2% required steroids. We also identified an acute toxicity of LSN pain in 10 patients (14.1%). Patients rated this LSN pain between moderate and severe; median time to LSN pain was 2 days (range 1-6 days). For LSN pain, management was conservative for 3 (30%) patients and symptoms self-resolved. The other 7 patients required ibuprofen and acetaminophen treatment; 2 of these patients had persistent symptoms and one was treated with topical hydrocortisone and gabapentin and the other with a burst of methylprednisolone. Dosimetric analysis of the lumbosacral nerve plexus area did not detect a statistically significant difference in dose parameters between symptomatic and asymptomatic patients. Conclusions: We have identified acute toxicities in patients treated with short course hypofractionated radiation, including diarrhea, rectal pain requiring steroid treatment, and previously underappreciated neuropathic lumbosacral pain. Toxicities mainly occurred within one week of treatment and resolved. Further analysis will seek to identify predictive factors of these acute toxicities and to determine whether there is a correlation between these observed acute toxicities and long-term outcomes. Research Sponsor: None.

93 Poster Session

Median Number of Lines of

Prior Therapies (range) , 46, 4 mo (95% CI 38, 1) for MR and 30, 7 mo (95% CI 23, 4) for HiR pts (p=0,02); ECOG performance status was an independent prognostic factor (p=0,002) for OS. Median PFS was 88,0 mo (95% CI 6,9-169,0) for LR, 12,9 mo (95% CI 9,1-16,7) for MR and 7,7 mo (95% CI 5,9-9,4) for HiR pts (p,0,001); positive resection margins and prior induction chemotherapy (CT) were additional independent negative prognostic factors for PFS (p,0,001). Conclusions: These results suggest a significant association between relapse risk after surgery for CRLM and both OS and PFS. The CERR score can be used to select potential candidates for CRLM surgery and improve the impact of this intervention in pts with CRC. The link between induction CT and worse survival may reflect selection bias as these pts possibly had a higher volume of disease and therefore received initial systemic therapy. Prospective studies are required to confirm these results. Research Sponsor: None.

3 (1-11) 2 (0-6) 2 (1-7) 1 (1-3) 3 (1-8)

97 Poster Session

First-line Nivolumab in patients (pts) with advanced gastrointestinal (GI) cancers with high plasma tumor mutational burden (pTMB): Results from a SCRUM-Japan GOZILA phase II trial. First Author: Yoshiaki Nakamura, Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan Background: TMB is a biomarker for immune checkpoint inhibitors (ICIs). Analysis of circulating tumor DNA (ctDNA) has the potential to non-invasively identify pts likely to benefit from ICIs by assessing pTMB. We conducted a phase II basket trial as part of the SCRUM-Japan GOZILA umbrella/basket trial to evaluate the efficacy and safety of nivolumab monotherapy in pts with advanced GI cancers with high pTMB.

Methods: Eligibility criteria included histologically confirmed unresectable or recurrent GI cancers; ECOG PS of 0 or 1; refractory or intolerant to the standard therapies; and high pTMB identified by Guardant360 CDx, a 74-gene ctDNA assay. Pts received intravenous nivolumab monotherapy of 360 mg every 3 weeks until progressive disease. The primary endpoint was objective response rate (ORR) per investigator assessment. The pTMB score was calculated by adjustment of mutation count by tumor fraction, and initial pTMB thresholds were determined based on previously reported ORR for ICI treatment for each GI cancer in the cohort. The cohort 2 proceeded only for esophageal cancer, and an ultra-high TMB cohort was created to include pts in the top 2% for pTMB scores.

Results: Fifty-one pts with high pTMB in the cohort 1/2 (n=32) and the ultra-high TMB cohort (n=19) were enrolled. The median duration of follow-up was 7.5 months (range, 0.9-51.3). Deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H) was observed in 1 pt in cohort 1/2 and 2 in ultra-high TMB cohort. The number of major comorbidities was computed using ICD-9-CM/10 codes within 1 year prior to 2L (Quan, 2005) . Time to next treatment (TTNT) was defined from the start of 2L to the start of next line treatment (excluding maintenance). For survival outcomes, the median survival time and 95% confidence interval (CI) were estimated using the Kaplan-Meier method. Uni-and multi-variable analyses (UVA and MVA) were performed with the cox proportional hazard model. All covariates were evaluated in UVA, and those significant were included in MVA with adjusted hazard ratio (HR) and 95% CI. Results: 3,215 patients met criteria; most previously received a biologic with 1L (70.5% prior anti-angiogenesis and 5.9% prior anti-EGFR) and had 0 structured major comorbidity diagnoses (82.1%). In the 2L, FOLFIRI was the most used chemotherapy backbone (90.6%, vs iri 9.4%), 79% of patients also received a biologic, and patients who received FOLFIRI were younger (median age 61 vs 65 years) and had better ECOG performance status (87.8% vs 81.8% ECOG 0-1).

105 Poster Session

A retrospective analysis of the prognostic impact of KRAS G12D mutation in patients with RAS-mutated metastatic colorectal cancer. First Author: Toshiharu Hirose, National Cancer Center Hospital, Chuo City, Japan Background: KRAS is an oncogene that is mutated in about half of all metastatic colorectal cancers (mCRC). Recently, a novel therapy targeting KRAS G12C mutation has demonstrated promising efficacy for advanced solid tumors, including mCRC. A therapy targeting KRAS G12D mutation is also under development and promising efficacy is expected. However, the prognostic impact of the KRAS G12D mutation in patients with mCRC is still unclear. Methods: We retrospectively reviewed the medical records of patients with mCRC harboring RAS mutation who received first-line chemotherapy between January 2013 and December 2022 at our hospital in Japan. We compared the survival outcomes between patients with KRAS G12D mutation (G12D group) and those with non-KRAS G12D mutations (non-G12D group) in terms of progression-free survival (PFS) and overall survival (OS), using the Kaplan-Meier method and the log-rank test.

Hazard ratios (HRs) and 95% confidence intervals (95%CIs Results: 10 pts with advanced CRC and BRCA1 mut (n=3), BRCA2 mut (n=5), or both (n=2) were enrolled from February 2020 to June 2021. Germline or somatic status was not reported in 7 of 10 pts, 2 pts had somatic BRCA2 muts and 1 pt had a germline BRCA2 mut. 2 pts had left sided tumors, 2 had right sided, 3 had rectal tumors, and 3 pts had tumors that were site undetermined. All pts were evaluable for efficacy and toxicity. Median TTD (95% CI) of the AAIs and anti-EGFR groups in 2L were 6.2 mo (5.8-6.9) and 6.1 mo (5.2-7.4), respectively. Among patients with recurrence within 6 mo (72.6%), the median TTD (95% CI) for AAIs and anti-EGFR groups were 6.1 mo (5.5-6.5) and 5. Background: Standard first-and second-line chemotherapy regimens for mCRC are FPDbased. In the phase 3 SUNLIGHT trial, the addition of BEV to FTD/TPI significantly improved overall survival (OS) compared with FTD/TPI alone in patients with mCRC who had received no more than two prior chemotherapy regimens. Here, we assessed the effect of timing of prior exposure to FPD on efficacy outcomes among patients treated in SUNLIGHT. Methods: In this post-hoc analysis, OS, progression-free survival (PFS), and disease control rate (DCR) were assessed in patients treated with FPD within 2 months of enrollment (,2 months FPDfree exposure) and patients who had not received FPD for $2 months prior to enrollment ($2 months FPD-free exposure). Differences in OS between FTD/TPI + BEV and FTD/TPI alone were assessed in each subgroup. The Kaplan-Meier method and log-rank test were used to compare differences in OS/PFS; DCR was compared using Fisher's exact tests. The hazard ratio (HR) for OS was estimated using a Cox proportional hazards model. Results: Of 246 patients randomized to FTD/TPI + BEV, 79 had $2 months FPD-free exposure and 167 had ,2 months FPD-free exposure. Median OS (95% CI) was 11.8 months (9.4-not estimable) for patients with $2 months FPD-free exposure and 10.5 months (8.6-11. 3) for patients with ,2 months FPD-free exposure (P=0.095); median PFS was 6.7 months (4.6-7.5) and 5.2 months (4.2-5.7), respectively (P=0.043). The DCR among patients treated with FTD/TPI + BEV was 79.8% for patients with $2 months FPD-free exposure and 64.7% for patients with ,2 months FPD-free exposure, with a between-group difference of 15.1% (95% CI: 3.6%-26.5%; P=0.018). Of 246 patients randomized to FTD/TPI alone, 91 had $2 months FPD-free exposure and 155 had ,2 months FPD-free exposure. Median OS was 9.3 months (6.7-10.9) and 6.8 months (6.0-7.8) for patients with $2 and ,2 months FPD-free exposure, respectively (P=0.106) and median PFS was 3.6 months (2.1-3.9) and 2.1 months (2.0-2.7) (P=0.002). The between-group difference in the DCR was 13.8% (50.6% vs. 36.7% for $2 and ,2 months FPD-free exposure; 95% CI: 1.0%-26.6%; P=0.044). Compared with FTD/TPI alone, FTD/TPI + BEV resulted in longer OS in both the $2-month (HR 0.61, 95% CI: 0.41-0.93) and ,2-month (HR 0.59, 95% CI: 0.45-0.78) groups, respectively. Conclusions: Owing to imbalances between the $2and ,2-month FPD-free exposure groups, the data need to be interpreted with caution. However, with both FTD/TPI + BEV and FTD/TPI alone, OS, PFS, and DCR were numerically higher in patients with $2 months FPDfree exposure than in those with ,2 months FU-free exposure, potentially reflecting the better prognosis of the former group. The survival benefits of adding BEV to FTD/TPI were maintained regardless of the timing of exposure to FPD prior to enrollment.

116 Poster Session

Quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) analysis of fruquintinib + best supportive care (BSC) compared with placebo + BSC in metastatic colorectal cancer (mCRC): Results from the FRESCO-2 trial. First Author: Sebastian Stintzing, Department of Hematology, Oncology and Cancer Immunology, Charité -Universitätsmedizin Berlin, Berlin, Germany Background: As mCRC and its treatment can adversely impact quality of life (QoL), maintaining QoL is an important treatment goal in addition to improving survival outcomes, particularly as patients progress through lines of therapy. In the global, randomized, double-blind, phase 3 FRESCO-2 trial (NCT04322539), fruquintinib (F) + BSC vs placebo (P) + BSC demonstrated significantly improved overall survival (OS) (median 7.4 months vs 4.8 months; HR 0.66, 95% confidence interval [CI] 0.55-0.80) and progression-free survival, with a manageable safety profile and without deterioration of QoL in heavily pretreated patients with refractory mCRC. The objective of this post-hoc Q-TWiST analysis was to assess the quality-adjusted survival benefit of F + BSC in the context of the FRESCO-2 trial. Methods: The Q-TWiST analysis was applied to all 691 randomized patients from FRESCO-2 (F + BSC n=461 vs P + BSC n=230). Survival time of each patient was partitioned into 3 health states: time spent with treatment-emergent adverse events of CTCAE grade 3 or 4 before disease progression (TOX), time before disease progression without toxicity (TWiST), and time between disease progression and death or censoring (REL). Assuming utility coefficients of 1 for TWIST and 0.5 for TOX and REL, Q-TWiST was calculated as the utility-weighted sum of the time spent in each health state. The mean time spent in each of the 3 health states was calculated for each treatment group using Kaplan-Meier analysis, and a 95% CI for the difference between treatment was calculated using the nonparametric bootstrap method. Results: Q-

117 Poster Session

Neoadjuvant botensilimab plus balstilimab in resectable mismatch repair proficient and deficient colorectal cancer: NEST-1 clinical trial. First Author: Pashtoon Murtaza Kasi, Weill Cornell Medicine, Englander Institute of Precision Medicine, NewYork-Presbyterian Hospital, New York, NY Background: There is an unmet need to have an effective systemic immunotherapeutic option for patients with mismatch repair proficient/microsatellite stable (pMMR/MSS) colorectal cancer. The neoadjuvant platform presents an ideal setting as a window of opportunity to evaluate new drugs. The NEST-1 trial explored the safety and efficacy of neoadjuvant botensilimab (BOT), an Fc-enhanced next-generation anti-CTLA-4 antibody, alongside balstilimab (BAL; an anti-PD-1 antibody) in patients with colon and rectal cancer who were candidates for surgery. Methods: NEST-1, was a single-arm trial testing the feasibility, safety, and efficacy of the BOT/BAL regimen in neoadjuvant settings for patients with colorectal cancer before resection. All patients received 1 fixed dose of 75 mg of BOT and 2 fixed doses of 240 mg of BAL 2 weeks apart. Patients could proceed to surgery 1 week after completion of the 2 nd dose of BAL. Less than 25% of patients were allowed to be mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H). Other inclusion and exclusion criteria were in accordance with ongoing immunotherapy-based clinical trials. Results: The study met its primary endpoints. A total of 12 patients with colon and rectal cancers were safely treated with the BOT/BAL combination without delaying surgery or increasing the risk of any severe adverse events. Significant regression of tumors was noted (Table ). Spatial biology analyses on pre-treatment biopsy and post-treatment surgical samples using RareCyte Inc. revealed novel mechanisms of action and patterns of response/regression; most of the viable tumor if present was superficially oriented near the luminal surface. ctDNA reductions correlated with pathological responses. Conclusions: BOT/BAL appears to be a safe and active regimen both in pMMR/MSS and dMMR/MSI-H colon as well as rectal cancers. The downstaging observed may spare surgery and/or adjuvant chemotherapy. Given the findings, the study has now expanded to two additional cohorts that are now enrolling to study further the dosing, and timing and/or need for surgery in these patients. Clinical trial information: NCT05571293. Research Sponsor: Agenus Inc. patients 2, 3, 7, and 9 ).

First report of the randomized phase III study of bi-weekly trifluridine/ tipiracil (FTD/TPI) plus bevacizumab (BEV) vs. FTD/TPI monotherapy for chemorefractory metastatic colorectal cancer (mCRC): JCOG2014 (ROBiTS). First Author: Hironaga Satake, Department of Medical Oncology, Kochi Medical School, Nankoku-City, Japan

Background: FTD/TPI has been widely used as one of the standard therapies in the late-line treatment for patients with mCRC, and the efficacy of FTD/TPI plus BEV combination was also recently reported in the SUNLIGHT trial. However, the combination of FTD/TPI plus BEV increased the frequency of hematologic toxicity. On the other hand, several phase II studies suggested that modifying the FTD/TPI schedule in combination with BEV from 4-week intervals (2 weeks-on, 2 weeks-off) to bi-weekly dosing (1 week-on, 1 week-off) reduced hematologic toxicities without reducing efficacy. Therefore, we commenced a phase III study to confirm the superiority of bi-weekly FTD/TPI plus BEV to 4-week intervals FTD/TPI monotherapy. Methods:

120 Poster Session

Trifluridine/tipiracil (TAS-102) in combination with anti-EGFR re-challenge versus TAS-102 plus anti-VEGF in patients with mCRC who experienced first-line anti-EGFR-based chemotherapy. First Author: Ching Tso Chen, De-Department of Oncology, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan Background: TAS-102 is one of the standard treatments for refractory metastatic colorectal cancer (mCRC). Add-on bevacizumab to TAS-102 has been proved to improve progression-free survival (PFS) and overall survival (OS). However, the two strategies of combination with anti-EGFR or anti-VEGF in RAS/RAF wild-type mCRC patients have not been compared. Methods: We retrospectively collected mCRC patients who received TAS-102 treatment from December 2018 to March 2023 at National Taiwan University Hospital. The key inclusion criteria included RAS/RAF wild-type, first-line treatment with anti-EGFR therapy, and TAS-102 in combination with anti-EGFR re-challenge, or with anti-VEGF therapy. Concurrent use of other chemotherapies was allowed. The patients with combination duration less than 4 weeks were excluded. Results: A total of 30 patients were enrolled. There were 20 patients who received TAS-102 plus anti-EGFR rechallenge, and 10 were treated with TAS-102 plus anti-VEGF. The median treatment line of TAS-102 combined with targeted therapies was 5 (Range 3-11). There was no significant difference in baseline characteristics between the two groups (Table ). For TAS-102 plus anti-EGFR vs VEGF, the ORR was 30.0% vs 0%, and the DCR was 70.0% vs 30.0%, respectively. The median PFS was 4.0 vs 2.3 (p=0.389) months, respectively. The median OS was 12.67 vs 9.93 (p=0.722) months, respectively. Conclusions: TAS-102 plus anti-EGFR re-challenge showed a higher ORR than TAS-102 plus anti-VEGF. The PFS and OS were comparable in both arm and numerically longer in the and offering non-operative management (NOM). This phase II study sequences FOLFOX followed by SCRT with the primary aim of evaluating the rate of cCR. Methods: Treatmentnaïve adults with non-metastatic clinical T2-3N0 or T1-3 with N1-2a rectal adenocarcinoma were eligible to participate in this open label, single-arm clinical trial. Low rectal tumors defined as patients requiring abdominoperineal resection were excluded. This trial evaluated TnT with 5-fluorouracil, leucovorin and oxaliplatin (mFOLFOX6) every 2 weeks for 10-12 cycles followed by SCRT. SCRT consisted of 25 Gy in 5 fractions to rectal tumor and 20 Gy in 5 fractions to lymph node regions. Primary endpoint was the rate of cCR, defined as normal digital rectal exam (DRE) and endoscopic evaluation with normal appearing mucosa or scar but no nodularity or ulcerations. Near complete response (nCR) was defined as DRE with smooth or minor mucosal abnormalities and endoscopic exam with superficial ulceration or erythematous scar. Those with cCR or nCR after TnT were offered NOM and close surveillance; all others underwent total mesorectal excision (TME). Secondary endpoints included 1-year disease-free survival (DFS) from time of cCR (for NOM) or time of TME, overall survival (OS), and R0 surgical resection rate. Results: Twelve patients enrolled with a mean age 51.4 years; 7 were male. Mean distance of the primary tumor from the anal verge was 9.7 cm. Median duration of follow-up was 3.1 years. Three patients (25%) achieved cCR and 1 achieved nCR. All 4 with at least nCR underwent NOM per protocol. The patient with nCR had local regrowth and underwent TME and all 3 patients with cCR remain free of disease on NOM.

In regards to secondary outcomes, 1-year DFS was 100%. Median OS was not reached. One patient had died at the time of analysis; this patient had lung nodules thought to be benign at enrollment but ultimately were deemed metastatic disease. All surgical resections were R0 with no local recurrence after TME. The study was closed early after published OPRA trial results demonstrated benefit of giving radiation first in TnT sequencing. Conclusions: Our study suggests that TnT with FOLFOX followed by SCRT may be a valid approach in treating LARC. In this small study, excellent local control was demonstrated with no local recurrence after TME and 25% of pts remaining on NOM at the time of analysis. The 33% of subjects offered NOM is much lower than the published 74% in OPRA, suggesting that chemo followed by SCRT may not be the most optimal approach if organ preservation is the primary treatment aim. Clinical trial information: NCT03781323. Research Sponsor: None.

123 Poster Session

A prospective multicenter phase II trial of total neoadjuvant therapy for locally advanced rectal cancer in JAPAN: ENSEMBLE-1 study. First Author: Yoshinori Kagawa, Department of Gastroenterological Surgery, Osaka General Medical Center, Osaka, Japan Background: The short-and long-term prognosis of total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC) is elucidated in the world. We evaluated the feasibility and safety of TNT for patients with LARC in Japan. Methods: This prospective, multicenter, open-label, single-arm phase II trial was conducted at five institutions. The key eligibility criteria were age $20 years, LARC within 12 cm from the anal verge, and cT3-4N0M0 or TanyN+M0 at the time of diagnosis that enabled curative resection. Preoperative short-course radiation therapy (SCRT) 5 Gy 3 5 days (total 25 Gy) + CAPOX (6 courses) followed by total mesorectum excision (TME) was the treatment protocol. Non-operative management (NOM) was allowed if clinical complete response (cCR) was obtained in the preoperative evaluation. The primary endpoint was the pathological complete response (pCR) rate. With a pCR rate threshold of 5%, an expected value of 28%, a one-sided significance level of 5%, and a power of at least 80%, the sample size required by the exact binomial distribution method would be $19 patients. Considering a few dropouts, ineligible cases, and patients in which resection was not performed, the target sample size was set to 27 patients. Results:

125 Poster Session

Regorafenib plus FOLFIRI with irinotecan dose escalated according to UGT1A1 genotyping in patients with metastatic colorectal cancer. First Author: Chao-Yuan Wang, Division of Colorectal Surgery, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan Background: This multicenter, phase II, randomized, open-label, 2-arm parallel trial aims to compare the efficacy and safety profiles of regorafenib plus irinotecan doseescalated FOLFIRI according to UGT1A1 genotyping with regorafenib alone in previously treated patients with metastatic colorectal cancer (mCRC). Methods: A total of 153 patients were planned to randomize at a ratio of 2:1 for receiving regorafenib plus FOLFIRI (arm A, 102 patients) or regorafenib alone (arm B, 52 patients), respectively. For both arms, regorafenib were given for 21 consecutive days (Day 1 to 21) of each 28-day cycle at a maintained dose of 120 mg. However, for arm A, patients received regorafenib plus FOLFIRI with dose-escalated irinotecan according to UGT1A1 genotypes. FOLFIRI were on the first day of each 28-day cycle only. The primary end point was progressionfree survival (PFS). Secondary end points included overall survival (OS) and disease control rate (DCR), and adverse events (AEs). Results: Finally, a total of 116 patients were enrolled to be analyzed, including 74 in arm A and 42 in arm B. The significantly better PFS was observed in arm A, 4.8 and 3.0 months, respectively (p = 0.016). Moreover, in patients withRAS wild type, the significantly better PFS was observed in arm A, 6.3 and 2.1 months, respectively (p = 0.003). The OS was not significantly different between group A and B, 9.8 and 12.6 months, respectively (p = 0.970). However, in patients with RAS wild type, the trend of better OS was observed in arm A, 14.3 and 6.9 months, respectively (p = 0.158). The marginally significant better DCR was observed in arm A, 55.4% and 38.1%, respectively (p = 0.055). The marginally significant better DCR was observed in arm A, 55.4% and 38.1%, respectively (p = 0.055). Combination treatment of regorafenib plus FOLFIRI was independent favorable prognostic factor for PFS (P = 0.008; hazard ratio [HR], 1.892; 95% CI, 1.182 -3.027). Regarding severe AEs, there were no significant differences between the two groups (all P.0.05 Transcriptomic analysis of zelenirstat treated cell lines identified an expression signature that predicts cancers most likely to be responsive to NMT inhibition; high sensitivity scores were seen in colorectal carcinomas and diffuse large B-cell lymphoma. The objectives of this phase I study were to determine the safety, tolerability, and maximum tolerated dose (MTD) of zelenirstat monotherapy in patients (pts) with refractory cancers. Methods: Pts with advanced solid malignancies or relapsed/ refractory B-cell lymphomas were dose escalated with daily oral zelenirstat in 28day cycles until progressive disease or dose-limiting toxicity (DLT). Results: Between September 2021 and July 2023, pts received 28-day cycles of zelenirstat ranging from 20 mg/d to 280 mg/d. In 21 evaluable patients, DLT was not observed up to and including the 210 mg/d cohort. Gastrointestinal DLTs were seen in the 280 mg/d cohort, establishing 210 mg/d to be the MTD. In doses up to and including 210 mg/d, gastrointestinal adverse events were the most common, reported in 29% of pts; these were primarily Gr 1 or 2 diarrhea, nausea or vomiting. Transient Gr 2 thrombocytopenia was seen in 3 pts. Zelenirstat did not induce neuropathy, alopecia, or prolong QT intervals. Plasma concentrations peaked between 1h and 4 h, terminal half-lives were 6.7 to 12 h, and steady state was achieved by day 8. Proton pump inhibitors lowered exposure and were prohibited in the higher dose cohorts. At 100 mg/d and higher, trough plasma concentrations exceeded the levels predicted to be therapeutic. Background: Maintenance treatment with capecitabine and bevacizumab after capecitabine, oxaliplatin, and bevacizumab therapy in metastatic colorectal cancer (mCRC) is shown to be effective with observation as an acceptable alternative. Metastatic burden might aid in shared decision-making and the aim of this exploratory analysis is to assess the prognostic and predictive value of number and total volume of metastases in mCRC patients included in the CAIRO3 study. Methods: Patients in the CAIRO3 study with liver and/or lung metastases were included. Every individual liver and lung metastasis was counted and volumes were assessed using deep-learning automatic segmentation software (SAS analytical platform and Philips IntelliSpace). Lymph node metastases were counted manually. Each scan was supervised by a dedicated radiologist. Kaplan-Meier analyses were used to estimate progression-free survival (PFS) and overall survival (OS) using log-rank testing for statistical comparison. Hazard ratios (HR) were estimated using Cox regression models. Results: A total of 156 patients were included with 154 OS events, in which 8198 metastases were identified: 5179 were liver metastases, 2835 lung metastases, and 184 lymph node metastases. Patients had a mean age of 63 years and 67% were male. At randomization, the median number of metastases was 9 and mean total metastatic volume was 116 cm 3 . HR, 1.77; p = 0.01) . PFS was similar between the two groups (median PFS, 13.0 vs. 15.8 months; HR, 1.18; p = 0.39). Fewer patients in the LR+ group received second-line CTx compared with the LR-group (68 vs. 83%, p = 0.06). The proportions of patients with PS $ 1 (78 vs. 52%, p = 0.007) and PS deterioration at progression after first-line CTx (59 vs. 27 %, p = 0.002) were higher in the LR+ group compared with the LR group-. The most common cause of PS deterioration in the LR+ group was LR-related pain (77%). Among patients with LR-related pain, the proportion of patients receiving subsequent second-line CTx was numerically lower in patients who did not receive palliative RT than in patients who did receive palliative RT until disease progression after first-line CTx (75 vs. 54%, p = 0.23). Multivariate analysis revealed that receiving subsequent second-line CTx was an independent prognostic factor for PPS in LR+ patients (adjusted HR, 4.77; p = 0.006).

The presence of LR is associated with poor prognosis in URRC, which may be due to worsening PS caused by LR-related symptoms and the lower proportion of subsequent CTx. Thus, palliative RT should be recommended more actively when LR becomes symptomatic. Research Sponsor: None.

The IFNg score was significantly lower in LMTK3 Q4 while the TIS score was significantly higher in LMTK3 Q4 (q , 0.0001). Conclusions: Our data show a strong association between LMTK3 gene expression and distinct molecular features and TME immune cell infiltration in CRC. These findings suggest that LMTK3 may be an important molecular factor that plays a role in determining the composition of the Background: In pts with CRC, the clinical usefulness of ctDNA testing after curative resection has been strongly suggested. Prognostic biomarkers are also needed for pts with resectable metastases to identify high-risk patients who may be spared unnecessary surgery or local ablation. We aimed to create a prediction model to estimate the risk of post-operative recurrence using an integrated analysis of preoperative ctDNA level and radiographic imaging. Methods: The GALAXY study (UMIN000039205) included 645 pts with newly diagnosed or recurrent CRC with resectable metastatic lesions. Pts without liver or lung metastases and those who had received chemotherapy within 3 months prior to ctDNA measurement were excluded. We used the ratio of preoperative ctDNA levels [mean tumor molecules (MTM)/mL] to tumor metastasis volume (mL) from radiographic imaging (ctDNA/volume) to predict recurrence. Cutoff ctDNA/volume values were determined from receiver operating characteristic curves using Youden index. Pts with above and below the cutoff values were defined as high and low risk, respectively. Disease-free survival (DFS) was calculated from the date of definitive surgical resection to first recurrence or death. Results: In this cohort of 110 pts with liver metastases and 24 with lung metastases, the median follow-up was 13.2 months (range: 0.7-30.9). The cutoff values for the ctDNA/volume model were 0.837 (liver) and 0.496 (lung) MTM/mL 2 . Among the pts with liver metastases, the high-risk group predicted by the ctDNA/volume model had a median DFS of 14.7 months (95% CI: 6.1-not reached) versus not reached (95% CI: not reached-not reached) in the low-risk group (HR = 3.6, P = 0.021). Among the pts with lung metastases, the median DFS was 2.9 months (95% CI: Targeted sequencing was used for analysis, and mutations were considered positive if detected in either biopsy or surgical samples, with an allele frequency of 5% or higher and not classified as variants of unknown significance (VUS). Additionally, we examined 334 cases of locally advanced rectal cancer that underwent preoperative treatment using publicly available data in cBioPortal. Results: The median recurrence-free survival (RFS) was 1,415 days (range: 97-2,868) with 15 recurrences, and the median overall survival (OS) was 1,702 days (range: 97-2,868) with 8 deaths (6 from the original disease, 1 from other cancers, and 1 of unknown cause). Among the 4 cases that showed histological response to NAC (AJCC Tumor Regression Grade 0-1), there was 1 recurrence, but no deaths occurred. RFS and OS in TRG0-1 were favorable compared to TRG2-3, but the differences were not statistically significant (3-year RFS: 75% vs. 65%, P=0.557; 3-year OS: 100% vs. 92%, P=0.339). In targeted sequencing analysis, TP53 mutations were found in 32 cases, KRAS mutations in 19 cases, APC mutations in 14 cases, FBXW7 mutations in 5 cases, SMAD4 mutations in 4 cases, PIK3CA mutations in 3 cases, and NRAS mutations in 2 cases. Co-mutations were observed in 13 cases for TP53/KRAS, 8 cases for TP53/APC, and 5 cases for KRAS/APC. One case each of these co-mutations was observed in TRG0-1. FBXW7, SMAD4, PIK3CA, and NRAS mutations were not found in TRG0-1. In the publicly available database, TRG0-1 showed significantly better RFS and OS compared to TRG2-3 (RFS: P=0.002, OS: P=0.089). SMAD4 mutations were significantly more frequent in TRG3 (P=0.02 The associations between the QuantCRC features and pCR were evaluated using Wilcoxon rank-sum tests and logistic regression models while adjusting for primary tumor location and NAT.

Results: The identified 288 pts had the following demographics: median age 60, 59% male, 52% distal tumor, 42% TNT. Pts who achieved pCR had smaller pre-treatment tumors (p=0.03), higher TILS, and lower %immature (stroma) (Table 1 ). After multivariable adjustment, higher TILS and lower %immature (stroma) remain to be significantly associated with a higher likelihood of pCR. A higher % mature (stroma) and %mature stroma (tumor bed) were also identified, in multivariable models, to be associated with a higher rate of pCR Methods: In this study, using a total of 30 colorectal cancer patient samples from Windsor Regional Hospital Cancer Program, we performed comprehensive targeted gene sequencing to identify single nucleotide variants, small insertions/deletions, copy number variants in over 500 genes that are implicated in cancer. Mean age of the patients in this study was 44 years and only patients without any personal or family history of colon cancer /other malignancies or IBD were enrolled in the study. Results: While identifying previously known colorectal cancer associated genetic variants, our preliminary data shows distinct missense mutations in several genes potentially contributing to the development and progression of cancer in these patients. In addition to showing pathogenic mutations in colorectal cancers associated genes, such as PIK3CA (H1047R, E545K, E545G, R93W, V344A), KRAS (G12V, G12D, A146T) and APC, our study showed recurring missense mutations in several genes including AXIN2, ALK, CDKN1A, MAP3K1, ROS1, EPCAM, KDM5A and AURKA in over 50% of our samples. Conclusions: The genomic profiling performed using biopsies from young colorectal cancer patients through this study provides a unique ability to identify the potential "genomic triggers" for the development and progression of cancer in young sporadic colorectal cancer patients. This information can not only be used to develop targeted treatment options for these patients but also to design new screening protocols as well as optimal surveillance strategies. Research Sponsor: Windsor Cancer Centre Foundation.

Serum angiopoietin-like protein 2 level in patients who received bevacizumab-containing chemotherapy for metastatic colorectal cancer.

First Author: Jung Hoon Kim, Pusan National University Yangsan Hospital, Yangsan-Si, South Korea Background: Anti-angiogenic agents are important for treating patients with advanced colorectal adenocarcinoma, however, their efficacy is not long-lasting and survival benefits are modest. Reliable biomarkers and novel targets for angiogenesis are still required in this era. Angiopoietin-like protein 2 (AGLP-2) is an emerging biomarker for angiogenesis in cardiovascular disease, but its role in the oncology area is yet to be elucidated. Methods: Serum samples from patients with advanced colorectal carcinoma treated with bevacizumab-containing chemotherapy were retrospectively studied. Blood samples at baseline and at disease progression of the first line systemic therapy were selected. Serum angiopoietin-like protein 2 (AGLP-2) concentrations were measured using ELISA kit, serial changes, and the relationship with progression-free survival and overall survival on the systemic therapy were statistically analyzed. Results: 68 patients were enrolled. Their median age was 66 years old (range, 38-82), and 14 (20.6%) patients had metastatic lesions at 3 or 4 organs. The median serum AGLP-2 levels at baseline and at disease progression (PD) were 41,618 pg/ml (95% confidence interval (CI) 34,560-40,713), and 49,706 pg/ml (95% CI 39,853-49,017), respectively. There was a tendency of difference between AGLP-2 levels at baseline and at PD (p=0.057

210 Poster Session

Identification of somatic alterations associated with brain metastases from a colorectal origin. First Author: James S. Strong, Memorial Sloan Kettering Cancer Center, New York, NY Background: Colorectal brain metastases (cBM) confer a devastating prognosis with survival of less than 13 months. Identifying genomic signatures to predict and guide treatment for these patients would be a valuable adjunct. This study evaluated genomic and clinicopathological features specific to cBM. Methods: cBM patients from the MSK-MET cohort were evaluated in comparison to other colorectal cancer patients with extracranial metastases (cOM). Clinicopathologic features and genomic alterations were analyzed with MSK-IMPACT, a targeted DNA sequencing panel for solid tumors and matched blood specimens. We considered mutations, copy number alterations, and fusions. Analyses of genomic features were restricted to microsatellite stable (MSS) patients. q-values were computed using Benjamini-Hochberg correction to account for multiple hypothesis testing. Patient record review identified patients with sequenced matched samples from the primary colorectal tumor and the brain metastases, which were then examined for loss and gain of assessed genetic alterations. Results: Of 130 patients with cBM identified from the cohort, 20 samples were from brain metastases, 52 from the primary CRC, and 58 from other metastatic sites. Average time to diagnosis of cBM was 3.5 years after primary colorectal cancer diagnosis and average time to death was 10 months after cBM diagnosis. Compared to the 3,383 cOM patients, cBM patients had significantly higher rates of both MSS CRC primaries (p,0.001, 122/130 cBM were MSS vs. 3,038/3,382 cOM) and primaries that originated in the rectum (p,0.002, with 38/130 cBM primaries from the rectum vs. 695/ 3,382 cOM rectal primaries). Somatic alterations in the KRAS, BRCA2, CDK8 and ERCC5 genes were significantly more frequent in patients with cBM compared to cOM patients (all p,0.001) (Table 1 ). Of the 9 patients who had matched primary and metastatic brain tissue sequenced, KRAS alterations were shared between the primary and brain metastasis in 2/9, ERBB3 and ERCC5 in 2/9, p53 in 6/9, and APC in 6/9 patients. In addition, newly acquired private alterations found only in the brain metastasis samples of matched patients included PIK3RI, ARID5B, NOTCH4, CYLD and SMAD4. Conclusions: We identify new genomic and clinical factors in cBM patients, including somatic alterations in potentially clinically actionable targets. To further explore potential clinical utility, these findings require validation in an independent cBM clinicogenomic dataset. Research Sponsor: None. We performed an integrated molecular and clinical analysis for 253 patients with MMRd sporadic CRC who received MSK-IMPACT genomic profiling at Memorial Sloan Kettering Cancer Center. Tumors were classified based on BRAF-V600E variants and gene fusion events. We evaluated the tumor burden of molecular alterations and disproportionate co-occurrence of specific driver variants of significance between each subtype. We used allele-specific FACETS analysis and MLH1 promoter hypermethylation assessments to infer the MMR-gene inactivation mechanism per tumor. We also examined differences in tumor phenotype and patient clinical outcomes. Patient progression-free-survival after treatment and overall survival was assessed with the Kaplan-Meier curves, and multivariable analyses were performed with Cox proportional hazards regression modeling. Results: Patients exhibited BRAF-V600Emutated (mut: n=178), BRAF-V600E-wt/gene-fusion positive (n=42), and BRAF-V600Ewt/fusion-negative (n=33) disease. Gene fusion events were mutually exclusive with BRAF-V600E variants and occurred in NTRK1 (n=13), NTRK3 (n=8; one with co-occurring NTRK1 fusion), RET (n=8), BRAF (n=8), ALK (n=5), and FGFR2 (n=1). BRAF-V600E-mut and fusionpositive tumors display similar predominant MLH1 silencing, WNT-signaling activators, and co-alterations. In contrast, BRAF-V600E-wt/fusion-negative tumors exhibit MLH1 inactivation associated with increased copy number alterations, and exhibit distinct cooccurring APC and TCFF7L2 variants. Both fusion-positive and BRAF-V600E-wt/fusionnegative tumors disproportionately arise in the transverse and left colon. In a multivariable analysis of 73 patients with stage IV MMRd CRC, fusion-positive status was an independently-significant, positive prognostic marker. For patients treated with immune checkpoint inhibitors (ICIs), tumor regression rates were high in BRAF-V600E-mut (63%; n=22/35) and fusion-positive (62.5%, n=5/8) subtypes, with slightly poorer outcomes in BRAF-V600E-wt/fusion-negative (40%, n=2/5) tumors. Patients with fusion-positive tumors exhibited clinical benefit to NTRK inhibition. Conclusions: In sporadic MMRd CRC, gene fusion-positive tumors exhibit an improved prognosis with similar molecular and treatment outcomes to BRAF-V600E-mut tumors. BRAF-V600E-wt/fusion-negative tumors are a unique sporadic MMRd subtype driven by alternative WNT-activation and potentially lower immunotherapy responses in small numbers of patients. Research Sponsor: NIH; Colorectal cancer alliance.

212 Poster Session

Prognostic value of circulating tumor DNA (ctDNA) testing in patients (pts) with rectal cancer after neoadjuvant therapy (NAT) and surgery. First Author: Sakti Chakrabarti, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Cleveland, OH Background: ctDNA is a highly prognostic biomarker for pts with GI malignancies. However, its utility in perioperative treatment decision-making is not established. We evaluated the association of post-NAT and post-surgical ctDNA status with outcomes in rectal cancer pts. Methods: We analyzed 1,656 longitudinal plasma samples from 257 rectal cancer pts (clinical stages I: 7%; II: 23%; III: 65%; IV: 5%). A personalized, tumor-informed assay (Signatera, Natera, Inc.) was used for ctDNA detection and quantification. In this cohort, 169 (66%) pts received NAT followed by surgery, 26 (10%) received surgery alone, and 62 (24%) had nonoperative management (NOM) after NAT. NAT included total neoadjuvant therapy (N=183), chemoradiation (N=33), and chemotherapy (N=15). Post-NAT time point (tp) was taken after completion of NAT and before surgery (surgery cohort) or between 2-16 weeks post completion of NAT (NOM cohort). Event-free survival (EFS) was defined as the interval from end of NAT to the date of clinical progression (NOM cohort). Disease-free survival (DFS) was defined as the interval from surgery to radiological recurrence. Results: The median follow-up was 619 (0-2,535) days. Pre-treatment ctDNA results were available for 50/257 pts; 94% (47/50) of whom were ctDNA+. Post-NAT tp was available for 87 pts, of whom 29.9% (26/87) were ctDNA+ and were less likely to achieve a clinical response to NAT [complete response: 8% (ctDNA+) vs. 51% (ctDNA-), p=0.0017]. Of the 87 pts with post-NAT tp, 48 underwent surgery, 39.5% (19/48) of whom were ctDNA+ post NAT and had worse pathological response [TRG score .2 (ctDNA+) vs. 0-2 (ctDNA-), p,0.001]. The remaining 39/87 pts underwent NOM, of whom 21.9% (7/39) were ctDNA+ and had significantly worse EFS compared to ctDNA-pts (HR: 7.6, 95% CI: 1.9-31, p,0.001). Among the pts who underwent surgery + NAT (N=195), ctDNA was measured in the MRD window (2-12 weeks post-surgery, prior to adjuvant therapy) for 128. Of these, 14.8% (19/128) were ctDNA+ (MRD+). Clinical recurrence was observed in 79% (15/19) of MRD+ pts and in 11% (12/109) of MRD-pts. Notably, of the MRD-pts who clinically recurred, 83% (10/12) did convert to ctDNA+ on subsequent blood draws. MRD+ pts had significantly worse DFS compared to MRD-pts (HR: 18, 95% CI: 7.9-39, p,0.0001). Similar results were observed regardless of whether the pts received NAT (DFS; NAT: HR=13, 95% CI: 5.8-31, p,0.0001; no NAT: HR=12, 95% CI:5.29-7957, p,0.001). Conclusions: Post NAT ctDNA status is associated with clinical/pathological response and survival outcomes. As such, ctDNA can potentially guide treatment decision-making in rectal cancer pts. The post-NAT tp was prognostic of recurrence in pts who had NOM. In pts receiving surgery, ctDNA status in the MRD window was highly prognostic of outcomes. Further studies are warranted to evaluate ctDNA-guided management in the post NAT and NOM settings. Research Sponsor: None.

52s COLORECTAL CANCER

Correlation of exploration of immune profile and genomic with microsatellite stable/tumor mutational burden-low colorectal cancer. First Author: Hassan Mohammed Abushukair, Jordan University of Science and Technology, Irbid, Jordan Background: Microsatellite stable/tumor mutational burden-low (MSS/TMB-L) tumors, represent the majority of colorectal cancer (CRC) patients and derive limited benefit from immune checkpoint inhibitors (ICI). Given the vast heterogeneity of this population, some patients may be candidates for ICI. Herein, we study the tumor immune microenvironment (TIME) and genomic correlates associated with favorable immune response in MSS/ TMB-L CRC patients. Methods: Using The Cancer Genomic Atlas Colorectal Adenocarcinoma (TCGA-COAD) cohort (n = 594), MSS patients (MSI Mantis score , 0.4) with TMB-L (,10 mutations/megabase) were identified. The CIBERSORT algorithm was used to calculate the fraction of 22 immune cells using RNA-seq data.

Relevant immune expression signatures from the CRI iAtlas were used to assess TIME profiles. An antitumor immune activity (AIA) score was constructed using CD8+ T cells, T regulatory cells, and M1 & M2 macrophage fractions. Enriched mutations in MSS/ TMB-L patients with favorable antitumor immune scores were identified and used to stratify patients into favorable and unfavorable immune profiles (FIP & UIP). Comparisons were made using the Mann-Whitney U T-test and Fisher's exact test. Results: We identified 430 (72.4%) MSS/TMB-L patients among the TCGA-COAD cohort. The AIA score ranged from -0.44 to 0.62 (higher scores denote favorable AIA activity). The majority of patients (77%) had scores , 0. Top enriched mutated genes associated with higher scores included HMX2, BBS12, IFNLR1, SLC30A2, WDR48, ZNF329, H4C11, PARD3B, ENAM, ASCC1, CCDC88B, CMKLR1, IL21, KLHL11, and OTOP2. Patients harboring a mutation in one or more of these 15 genes were categorized in the FIP group (n=50, 11.6%) and patients with no mutations were categorized in the UIP group (n=360, 88.4%). The FIP group had significantly (p , 0.05) higher levels of TMB, CD8+ T cells, activated NK cells, M1 macrophages, immunogenic SNV mutations, and cytotoxic activity while patients with UIP had higher levels (p , 0.05) of M2 macrophages, neutrophils, and a trend for higher regulatory T cells and TH17 cells. Gene set enrichment analysis showed upregulation of T cell proliferation, interferon signaling, and Fanconi anemia pathway in FIP. Compared to UIP, FIP patients had a trend for better diseasespecific survival after adjustment for CC subtype (colon vs. rectum) and age (HR: 0.26, 95% CI: 0.06-1.09, p = 0.066). Conclusions: Findings from this analysis highlight a subset of MSS/TMB-L CRC patients, with features of favorable anti-tumor immune response and unique mutation profile, that might derive benefit from immunotherapy. Further investigation is underway to further explore the genomic correlates in this subset of patients. Research Sponsor: None.

214 Poster Session

Surveillance of resected metastatic colorectal cancer utilizing circulating DNA. First Author: Nikolas Naleid, Department of Internal Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH Background: There is limited data to guide surveillance in patients with metastatic colorectal cancer (CRC) who have had curative resection using circulating tumor DNA (ctDNA) in addition to labs and imaging studies. Minimal residual disease (MRD) assays utilize circulating tumor DNA (ctDNA) for the purposes of monitoring for early recurrence and predicting therapeutic response. In this study, we aim to investigate the utility of ctDNA monitoring in the setting of resected metastatic CRC. Methods: Patients were identified through retrospective search at a tertiary care and several satellite settings to identify patients with metastatic CRC who had undergone curative resection and later had ctDNA monitoring (using Signatera assay). IRB approval was obtained for the study. We recorded demographic information (sex, race, age at diagnosis), disease characteristics (stage at diagnosis, site of primary cancer, site of metastasis), treatment regimens, clinical outcomes (recurrence, survival) and follow-up data.

216 Poster Session

"Choosing wisely" in oncology: The example of surveillance positron emission tomography-computed tomography (PET-CT) for patients with colorectal cancer (CRC) treated with curative intent. First Author: Roi Tschernichovsky, Davidoff Cancer Center Rabin Medical Center, Petah Tikva, Israel

Background: Healthcare overuse is a major challenge for healthcare systems. Professional guidelines, such as "Choosing Wisely", have been put in place to mitigate specific areas of overuse. We examined whether the rate of unwarranted PET-CT in CRC patients treated with curative intent was successfully reduced following the adoption of "Choosing Wisely". Methods: We used the large Clalit Health Services dataset in Israel to identify patients with CRC who received adjuvant chemotherapy for localized disease between January 2017-December 2021. We then examined the number of PETCTs performed for each patient.

133 Poster Session

Immune checkpoint blockade combined with targeted therapies to provide disease control in mismatch repair-proficient colorectal cancer with peritoneal metastases. First Author: Neal Bhutiani, The University of Texas MD Anderson Cancer Center, Houston, TX Background: Metastatic colorectal adenocarcinoma (mCRC) with proficient mismatch repair (pMMR) is associated with poor response to cytotoxic chemotherapy in the refractory setting, with a median overall survival (OS) of 10.8 months. Recent immunotherapy (IO) regimens utilizing a combination of immune checkpoint blockade (ICB) and tyrosine kinase inhibitors (TKIs) that suppress tumor-associated macrophages (TAMs) have shown promise for extra-hepatic, but not hepatic metastases. However, few studies include patients with peritoneal metastases (PMs) and the response rate of PMs to these therapies is unknown. We sought to examine the disease control rates (DCR) and OS of patients treated with PM who were treated with ICB regimens. Methods: Patients with pMMR tumors treated with ICB and TKI after progression on 1st and 2nd-line therapy from 2015 to 2022 were identified. Date of start of therapy, end of therapy, last follow up and vital status were determined from the medical record. Radiographic disease response within each metastasis site at 6 months and at last follow-up on therapy was determined for each patient. Overall survival was estimated using the Kaplan-Meier method. Results: A total of 93 patients treated with an ICB and TKI after at least two lines of cytotoxic systemic therapy were identified. Five were excluded due to dMMR/MSI-H status and eight due to lack of follow-up. A total of 33 patients with PM, with or without other metastases, had a median follow-up on therapy of 6.1 months and median follow-up until death or censoring of 9.8 months. Median OS was 15.1 (9.7-29.5) months, and 18-month survival was 43% (95%CI: 24-62%). OS was not associated with either BRAF (HR 0.98, p=0.98) or RAS (HR 1.50, p=0.37 ) mutation status. Partial response of PM was noted in 5 patients (15%), stable disease in 14 (42%) and progressive disease in 14 (42%), resulting in DCR of 57%. Disease control for all metastatic sites was noted in 9 (27%) of patients, and median OS was not reached at 2 years.

Median OS for patients without peritoneal progression was 22.0 months [12.3-NR], and PM progression was associated with worse OS (HR 0.66, p=0.024). A total of 32 patients with any metastatic site were treated for at least 6 months. Median follow-up was 16.1 months for this cohort. DCR at 6 months for CRLM was 23% (3/13), PM was 58% (14/24, p=0.08 vs CRLM) and for LM was 62% (8/13, p=0.11 vs CRLM)

140 Poster Session

A phase I dose-escalation study of an all-in-one 5-fluorouracil and leucovorin co-formulation administered after failure of standard treatment. First Author: Daniel Brungs, Cancer Care Wollongong, Wollongong, NSW, Australia

Background: 5-fluorouracil (5-FU) and its biomodulator leucovorin (LV) are an efficacious treatment option for various solid tumours, and are considered the backbone of therapy for colorectal cancer. Standard administration schedules require sequential administration of the two agents due to their chemical incompatibility; given the importance of LV in modulating 5-FU activity, their simultaneous administration is expected to enhance anti-tumour efficacy.

Deflexifol is an all-in-one injectable reformulation of 5-FU and LV at physiological pH. An initial phase I trial demonstrated the safety and efficacy of Deflexifol when administered as a bolus or infusion, with a maximum tolerated dose (MTD) of $25% more 5-FU than established for standard regimens. This subsequent phase I study sought to investigate Deflexifol administered as a combined bolus and infusion schedule. Methods: Patients with advanced malignancy who had failed standard treatment were administered Deflexifol as a bolus followed by a continuous 46-hr infusion. The infusional dose was escalated across four levels (2400 mg/ m 2 to 3800 mg/m 2 ) in the absence of Dose Limiting Toxicity using a traditional 3+3 design; the bolus dose was fixed at the previously declared MTD of 525 mg/m 2 . The stated Deflexifol dose represents the dose of standard 5-FU delivered. Primary trial objectives were to determine the safety and tolerability of a bolus plus infusion regimen of Deflexifol, with a secondary objective to determine the pharmacokinetics and MTD. Efficacy was an exploratory objective.

Results: Nineteen patients with mainly colorectal (n=13) and breast (n=4) cancers were enrolled and treated with Deflexifol. Approximately two-thirds of patients had previously received fluoropyrimidine treatment. Deflexifol was generally well tolerated, with the MTD declared as a 525 mg/m 2 bolus plus 3400 mg/m 2 infusion. Treatment-related toxicities were consistent with standard 5-FU/LV therapy; the most frequent Grade 1/2 adverse events were fatigue, mucositis, and diarrhea. Grade $3 adverse events were reported in 6/19 patients, including mucositis (2/19) and haematological toxicity (5/19). One treatment-related death occurred at the highest infusion dose level of 3800 mg/m 2 due to haematological toxicity.

Quantifiable 5-FU and LV concentrations were exhibited at all time-points. Disease control, including one partial response, was achieved in 9/13 evaluable patients. Conclusions: Deflexifol is safe and well tolerated at doses of 5-FU up to 40% higher than typically administered by the standard modified de Gramont regimen. 5-FU and LV co-exposure extended throughout the entire dosing period, substantially longer than reported for standard treatment. Disease control was achieved in 69% of patients. Clinical trial information: ACTRN12619001533189. Research Sponsor: FivepHusion.

141 Poster Session

Real world effectiveness of regorafenib in heavily pretreated patients with metastatic colorectal cancer. First Author: Anastasia Danilova, Moscow City Oncology Hospital 62, Krasnogorskiy Rayon, Russian Federation

Background: Metastatic colorectal cancer (mCRC) remains a challenge with a significant impact on patient survival and quality of life. Over the past decade, targeted therapies have emerged as promising treatment options for mCRC, including regorafenib. While clinical trials have established efficacy and safety of regorafenib in mCRC, based on the CORRECT and ReDos trials, the real-world utilization and outcomes associated with this therapy have gained increasing importance. This abstract presents a real-world data analysis focused on the use of regorafenib in patients with metastatic colorectal cancer in a community based comprehensive cancer center in Moscow, Russia. The data were collected from 2 outpatient medical oncology departments from 2018-2022 and we evaluated the real world patterns of use, effectiveness and safety. Methods: We evaluated all patients who were issued Regorafenib at a medical pharmacy of our cancer center. We evaluated all Regorafenib issued from 2018-2022 in our center -348 patients received Regorafenib and 311 of them were patients with metastatic colorectal cancer and identified patterns of use, toxicity and outcomes in this patient population. Results: The median age was 61.2 and 49.5% were female (50.5were male%) Primary tumor was right sided in 20.9% of all patients, left sided -49.1% and rectum in 29.9% De novo metastatic colorectal cancer was in 208 patients and 103 patients were those who progressed after initial treatment. Mutation status was identified in 91% of all patients. 46% had KRAS mutation, 3.8% were BRAF mutated and 4.2% were NRAS mutated. MSI status was known for 71% of the patients and it was negative. We understand the selection bias, because most of MSI-h patients would have gone on to receive immunotherapy rather than a TKI. The patients identified in our practice were more heavily pretreated (93.5% of them received more than 3 lines of prior therapy) and 1/3 of all patients were ECOG 2-3 performance status. Toxicity data were available only in 61% of the patients which reveals data caveats when using real world data outside of a clinical trial. Any grade toxicity was noted in 53% of all patients. Using Kaplan Myer Survival Analysis, the median PFS was 2 months and median OS was 5.3 months in the evaluated population.

The real world data analysis shows that while Regorafenib is another treatment option, and our data confirm the results of clinical trial, its utilization and use provides only modest clinical benefit for patients. Research Sponsor: None.

Subgroup analysis is underway to find a subgroup that could potentially benefit more from this therapeutic option. (39%) progressed on ICB. The majority of these were treated with monotherapy anti-PD1 (49, 83%) while only 10 (17%) were treated with combination ICB. Of those that progressed, 29 (49%) were considered intrinsic while 30 (51%) were considered adaptive. In the adaptive group, average TTP was 21 m. The majority progressed at a metastatic site (51, 86%) and at a prior site of disease (47, 80%). Progression was oligometastatic in 30 (51%) patients and systemic in 29 (49%) patients. The median TTP for oligometastatic progression was 9 m while median TTP for systemic progression was 4 m (p=0.005). The median OS for those with systemic progression was 17 m while the median OS for oligometastatic progression was not reached (p=0.027

Patient Characteristics

146 Poster Session

The interaction of radiotherapy and dual inhibition of BET and HAT/p300 in colorectal cancer. First Author: Michael Matthew Pennock, Montefiore Einstein Comprehensive Cancer Center, Bronx, NY Background: Colorectal cancer (CRC) is characterized by extensive DNA methylation at the promoters of tumor suppressor genes and enhanced activity of histone modifying proteins such as histone acetyltransferases (HATs) or histone readers such as bromodomain and extra-terminal domain (BET) proteins. BET inhibition has been associated with the reduced expression of DNA repair proteins and therefore can be used in combination with radiotherapy (RT) and chemotherapy. In the current study, we have evaluated the therapeutic potential of a clinical stage (phase 1) dual BET and CBP/p300 inhibitor, EP31670 (EP), in combination with RT. Methods: HCT116 CRC 2-D cultures were treated with EP 4 hours before RT. After pretreatment with EP (0, 0.1, 0.5, 1, 2, 5, and 10mM), cells were irradiated with various doses (0, 2, 4, 6, and 8Gy) of RT (300-kv xrays). Crystal violet (CV) assay at 48 hours post RT was used to determine growth inhibition and viability between the various drug, RT, and combination groups. Synergy between treatments was evaluated by estimating the combination index (CI) values via mass-action law CompuSyn calculations using CV data. CI values of ,1 from the growth inhibition assay suggested that EP synergized with RT for enhanced cytotoxicity in HCT116 CRC cells. Flow cytometry was used to assess DNA damage (gH2Ax), apoptosis and total death (Annexin V-PI assay), cell cycle analysis, and proliferation (EdU).

Results: There was a significant dose-dependent increase in the residual DNA damage at 6 hours (8Gy + EP 0.5mM vs. 8Gy, p,0.0001) and 24 hours (8Gy + EP 0.5mM vs. 8Gy, p=0.002) for combination therapy over RT alone. Four-hour treatment with EP promoted G2 cell-cycle arrest (8Gy + EP 0.5mM vs. 8Gy, p,0.001) and significantly reduced the number of HCT cells in S-phase (8Gy + EP 0.5mM vs. 8Gy, p,0.001) and proliferation (EdU) of the HCT cells (8Gy + EP 0.5mM vs. 8Gy, p=0.0003) compared to RT alone. There was a significant increase in apoptotic cells the combination group (8Gy + EP 0.5mM vs. EP 0.5mM, p=0.008) when compared to the unirradiated cells. The combination group also showed significant increase in the total death compared to RT alone (8Gy + EP 0.5mM vs. 8Gy, p=0.03) at the G1-S checkpoint.

155 Poster Session

Sex-based differences in the transcriptomic metabolic profiling in young onset colorectal cancer (YOCRC). First Author: Deepak Vadehra, Roswell Park Comprehensive Cancer Center, Buffalo, NY Background: The incidence of YOCRC has been rising rapidly. We recently showed that the YOCRC population has significantly different transcriptional metabolic and immune profiles than their older counterparts. In a separate study, we found that the metabolic and immune environments are affected by the sex of the patient. Based on these findings, we hypothesize that significant differences in transcriptional metabolic and immune profiles of males and females exist within the YOCRC population. The primary objective of this study was to identify those differences and compare them with the average onset colorectal cancer (AOCRC) population. Methods: Using TCGA (YOCRC N=48) and ORIEN CRC (YOCRC N=96) datasets, patients were separated into younger onset (,50) and older (.60) patient populations, comparing male and female transcriptional programs within each of the age groups. Subsequently, their transcriptional profiles were compared and assessed via differential gene expression analysis (DESeq2), gene set enrichment analysis (GSEA), immune deconvolution (TIMER2.0), and metabolic pathway analysis (MetaPhOR). These pathways were then mapped to assess transcriptional dysregulation, and patterns of predicted metabolic flux. Results: Our analysis revealed different transcriptional, metabolic, and immune signatures between males and females in differing age groups. Amongst the young patients, females were enriched for lipid metabolism (cholesterol and steroid metabolism), decreased macrophage signatures, and a proliferative phenotype. Conversely, males were enriched for glucocorticoid metabolism, urea cycle metabolites, metastasis, and CD4+ T Cell populations. Further, CTLA4 and PD-L1 response signatures were decreased in young males compared to young females, with a notable increase in inflammatory pathways. Immune deconvolution revealed no difference in the predicted infiltration of immune cells between younger males and females. In older patients (.60), females were enriched for lipid metabolism (testosterone, linoleic acid metabolism), CD8+ T cell signatures, and a proliferative phenotype. In contrast, males were enriched for lipid metabolism (cortisol), epigenetic alterations, and decreased macrophages. Like the younger population, CTLA4 and PD-L1 response signatures were decreased in older males, compared to older females, with a notable increase in inflammatory pathways.

159 Poster Session

An online rectal cancer tumoroid biorepository: A resource to facilitate multimodal data integration. First Author: Janet Alvarez, Memorial Sloan Kettering Cancer Center, New York, NY Background: Advancing genetic and computational technologies have increased the complexity and quantity of data available in the field of rectal cancer research. As such, there is a need for a centralized source of data to aid and organize current research efforts. To this end, our team has created a unique online biorepository of rectal cancer tumoroids which may serve as a resource for a community of researchers. Methods: The rectal cancer tumoroid biorepository was created in cBioPortal in 2015.

Organoids were derived from patient tumor samples (tumoroids). These samples represented multiple treatment timepoints and included primary, recurrent, and metastatic tumors. These tumoroids were further analyzed by various assays such as MSK-IMPACT and IC50 (to fluorouracil, FOLFOX, and FOLFIRI) to obtain patient-specific genomic and chemosensitivity data. A tumoroid profile was then created in cBioPortal for each sample. Clinical information was collected by chart review and annotated into the tumoroid profiles using the unique features of cBioPortal. These included interactive filters and graphical depictions of patient demographics, clinical and pathologic staging, treatment course, clinical response, overall survival, and disease-free survival. Results were organized in an intuitive visual display for convenient analysis. Novel features such as chemosensitivity plots and an interactive patient timeline were incorporated as well.

Results: In total, 401 rectal cancer tumoroids have been derived from 177 unique patients. Approximately 32% of the tumoroids were from patients 50 years or younger, and 63% of patients have a treatment naïve sample in our repository. Ten percent of tumoroids were derived from T1-T2 tumors, 56% from T3 tumors, and 17% from T4 tumors. Additionally, 14% of tumoroids were derived from primary tumor recurrences while 6% were derived from metastases. Of the 78% of tumoroids with completely annotated clinical data, 8% were MSI-H, 11% were clinical complete responders, and 5.5% were pathologic complete responders. Lastly, complete IC50 data with clinical correlates has been established for 20% of tumoroids. These data show that tumoroids with a high sensitivity to chemotherapy (FOLFOX) correlated with a 3.3-fold increase in clinical complete response rates in the corresponding patients (p=0.0263

171 Poster Session

Preclinical analysis and clinical validation to identify biomarkers of regorafenib efficacy in patients with metastatic colorectal cancer. First Author: Mitsukuni Suenaga, Clinical Oncology, Tokyo Medical and Dental University, Tokyo, Japan Background: In the identification of biomarkers for anticancer drugs, the lack of objectivity in the selection of candidate factors makes it difficult to interpret the mechanism. We performed preclinical analysis and translational validation study to identify the candidate cytokines for regorafenib efficacy in metastatic colorectal cancer (mCRC) patients. Methods: As a first preclinical process, we selected candidate cytokines according to our gene chip analysis using a panel of human cancer cell lines (JFCR39). We then validated predictive value of the cytokines in mCRC patients receiving regorafenib (discovery, N=54) and FTD/TPI (control, N=16). Blood samples were obtained at baseline (BL), before second cycle (2nd) and progressive disease (PD), and cytokine levels were measured using ELISA. Finally, we measured changes in cytokine levels and cell number in colorectal cancer cell lines treated with regorafenib. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier curves. Results: Our gene chip analysis showed association between high matrix metalloproteinase (MMP)-14 expression and high sensitivity to regorafenib, and the MMPs pathway was examined in blood samples. 8 .1 vs 4.6%) (q , 0.0001); however, these associations were no longer significant in pMMR/MSS tumors. In the pMMR/ MSS cohort, LMTK3 expression was highest in CMS4 (1.09 median TPM) followed by CMS2 (0.98), CMS1 (0.88), and lowest in CMS3 (0.70, all intergroup q , 0.05). LMTK3 high showed differential rates of mutations and copy number alterations (CNA) in several genes, including higher mutation rates of APC, TP53, and CDX2 CNA, while lower mutation rates of KMT2A/D, ASXL1, ATM, SMAD4, RNF43 and AMER1 in the overall cohort (q , 0.05). In the pMMR/MSS cohort, the associations with APC, TP53, SMAD4 and ATM mutations and CDX2 CNA still held true (q , 0.05). High LMTK3 was associated with higher immune CI in the TME, including B cells, neutrophils, NK cells, CD4+ T cells, monocytes and dendritic cells, while macrophages and Tregs were lower regardless of tumor MSI status (fold change: 0.83-2.4, all q , 0.0001).

Primary endpoint is event-free survival (EFS) (events: recurrence based on radiological assessment by blinded independent central review or pathological assessment of new lesions, disease progression precluding surgery, treatment (tx)-related toxicity precluding surgery, or death). Secondary endpoints include pathological response, OS, and safety. Disease assessments will consist of CT scans of chest, abdomen, and pelvis. Pts will undergo safety follow-up at end of tx and at 30 and 90 days after last dose. Efficacy will be assessed in all pts randomized (intent-to-treat) and safety in all pts who receive surgery or $1 dose of study tx. A stratified log-rank test will be used for primary analysis. The primary analysis for EFS with .90% power will be conducted after all pts have been followed for $3 years. An interim EFS analysis will be conducted ~12 months earlier. Recently amended eligibility criteria include inclusion of rectal cancer pts who have completed neo-adjuvant therapy and surgical resection, as well as enrollment of all stage II and III pts regardless of microsatellite stability status. The Oncotype Colon Recurrence Score® will be assessed on all pts from their surgical specimen, if criteria are met for this testing. ctDNA will be analyzed with an NGS-based tumor-informed MRD assay that identifies somatic genomic alterations from DNA derived from the patient's tumor tissue, subtracts germline variants, and detects a selected subset of tumor-specific (bespoke) ctDNA in their blood. All primary tumor specimens will undergo full exome and transcriptome sequencing using the Onco ExTra assay. If there is evidence of disease recurrence, the metastatic tissue will also undergo Onco ExTra testing and results will be shared with participants. The primary objective is to validate the association of postdefinitive therapy and pre-recurrence follow-up ctDNA positivity with recurrence-free interval (RFI). Further objectives are to assess the: sensitivity and specificity of ctDNA positivity for subsequent clinical recurrence; contribution of post-surgery baseline, postadjuvant therapy, and pre-recurrence follow-up ctDNA results on RFI; time from positive ctDNA to clinical recurrence in participants who had a positive ctDNA result; and to compare the Oncotype Colon Recurrence Score estimate of 3-year recurrence risk with the observed 3-year recurrence rate. The primary analysis will use a Cox proportional hazards regression applied to the RFI with ctDNA result (positive or negative) measured after surgery, or end of adjuvant therapy if received, and serially after that as a single, time-dependent covariate.

TPS243 Trials in Progress Poster Session

NRG-GI008: Colon adjuvant chemotherapy based on evaluation of residual disease (CIRCULATE-NORTH AMERICA). First Author: Christopher Hanyoung Lieu, University of Colorado Cancer Center, Aurora, CO Background: Currently, there are no biomarkers validated prospectively in randomized studies for resected colon cancer (CC) to determine need for adjuvant chemotherapy (AC). However, circulating tumor DNA (ctDNA) represents a highly specific and sensitive approach (especially with serial monitoring) for identifying minimal/molecular residual disease (MRD) post-surgery in CC patients (pts), and may outperform traditional clinical and pathological features in prognosticating risk for recurrence. CC pts who do not have detectable ctDNA (ctDNA-) are at a much lower risk of recurrence and may be spared the toxicities associated with AC. Furthermore, for CC pts with detectable ctDNA (ctDNA+) who are at a very high risk of recurrence, the optimal AC regimen has not been established. We hypothesize that for pts whose CC has been resected, ctDNA status may be used to risk-stratify for making decisions about AC. Methods: In this prospective phase II/III trial, up to 1,912 pts with resected stage IIB, IIC, and III CC will be enrolled.

Based on the post-operative ctDNA status using personalized and tumor-informed assay (Signatera Ô, bespoke assay), those who are ctDNA-(Cohort A) will be randomized to immediate AC with fluoropyrimidine (FP)+oxaliplatin (Ox) for 3-6 mos per established guidelines vs. serial ctDNA monitoring. Patients who are ctDNA+ post-operatively or with serial monitoring (Cohort B) will be randomized to FP+Ox vs. more intensive AC with addition of irinotecan (I) for 6 mos. One cycle of chemotherapy is allowed while awaiting ctDNA testing results for cohort assignment. The primary endpoints for Cohort A are time to ctDNA+ status (phase II) and disease-free survival (DFS) (phase III) in the immediate vs. delayed AC arms. The primary endpoint for Cohort B is DFS in the FP+Ox vs FP+Ox+I arms for both phase II and phase III portions of the trial. Secondary endpoints include prevalence of detectable ctDNA post-operatively, time-to-event outcomes (overall survival and time to recurrence) by ctDNA status, and the assessment of compliance to adjuvant therapy. Biospecimens including archival tumor tissue, as well as post-operative plus serial matched/normal blood samples, will be collected for exploratory correlative research.

LBA246 Oral Abstract Session

Pathological complete response (pCR) to 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) with or without durvalumab (D) in resectable gastric and gastroesophageal junction cancer (GC/GEJC): Subgroup analysis by region from the phase 3, randomized, double-blind MATTERHORN study. First Author: Yelena Y. Janjigian, Memorial Sloan Kettering Cancer Center, New York, NY

The full, final text of this abstract will be available at meetings.asco.org on the day of presentation and in the online supplement to the January 20, 2024, issue of the Journal of Clinical Oncology.

247 Oral Abstract Session

Pembrolizumab plus FLOT vs FLOT as neoadjuvant and adjuvant therapy in locally advanced gastric and gastroesophageal junction cancer: Interim analysis of the phase 3 KEYNOTE-585 study. First Author: Salah-Eddin Al-Batran, Krankenhaus Nordwest, UCT-University Cancer Center and Frankfurter Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest, Frankfurt, Germany Background: The phase 3 KEYNOTE-585 study (NCT03221426) evaluated neoadjuvant/ adjuvant pembrolizumab (pembro) or placebo (pbo) + chemotherapy (chemo) followed by adjuvant pembro vs pbo in locally advanced, resectable gastric or gastroesophageal junction (G/GEJ) cancer. A separate cohort evaluated pembro + FLOT (FLOT cohort). We report results from safety and efficacy analyses of the FLOT cohort at third interim analysis. Methods: In the FLOT cohort, patients (pts) with untreated, locally advanced, resectable G/GEJ cancer were randomized 1:1 to neoadjuvant pembro 200 mg IV Q3W (pembro gp) or pbo (pbo gp) Q3W for 3 cycles + FLOT (docetaxel, oxaliplatin, leucovorin, and 5-FU) Q2W for 4 cycles. After surgery, pts received adjuvant pembro or pbo Q3W for 3 cycles + FLOT Q2W for 4 cycles, then adjuvant pembro or pbo Q3W for 11 cycles. Endpoints evaluated included safety, pathCR rate (BICR), EFS (RECIST 1.1, by investigator), and OS in the ITT. Data cut-off at third interim analysis was 09 Feb 2023.

Results: A total of 203 pts were randomized (100 pembro + FLOT; 103 pbo + FLOT). Among these, 12 (6%) pts had cT1-T2, 161 (79%) had cT3, and 9 (4%) had cT4. 140 (69%) had N+ disease, and 79 (39%) had GEJ adenocarcinoma at baseline. Median follow-up was 31.6 months (mo) and 31.1 mo, respectively, at IA3. A total of 94 of 99 (95%) pts completed the neoadjuvant phase, 87 of 99 (87%) completed the surgery phase, and 45 of 77 (58%) completed adjuvant treatment. The R0-resection rate was 79% vs 80% in the pembro gp vs pbo gp, respectively. The pathCR rate was 17.0% (95% CI, 10.2-25.8) in the pembro gp and 6.8% (95% CI, 2.8-13.5) in the pbo gp, estimated difference (10.2% [95% CI, 1.3-19.7]). Median EFS was not reached (95% CI, 28.2-NR) in the pembro gp and 30.9 mo (22.8-NR) in the pbo gp (HR 0.79; 95% CI, 0.52-1.22). The 24-mo EFS rates were 66% and 57%, respectively. Median OS was not reached in either group (HR 1.04; 95% CI, 0.66-1.66). The 24-mo OS rates were 72% and 73%, respectively. Grade $ 3 drug-related AE rates in all phases combined were 76% and 63% in the pembro vs pbo gp, with serious drug-related AEs in 42% vs 20%, and surgery-related AEs in 20% vs 13%, respectively. A total of 3 (3%) vs 1 (1%) pt in the pembro vs pbo gp died due to a drug-related AE. A two-arm randomized open-label prospective design superiority phase III clinical trial to compare the efficacy of docetaxel-oxaliplatin-capecitabine/5 fluorouracil (DOC/F) followed by docetaxel versus CAPOX/mFOLFOX-7 in advanced gastric cancers (DOC-GC study). First Author: Anant Ramaswamy, Tata Memorial Hospital (HBNI), Mumbai, India

A randomized controlled phase III trial comparing thoracoscopic esophagectomy and open esophagectomy for thoracic esophageal cancer: JCOG1409 (MONET trial). First Author: HIROYA TAKEUCHI, Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan Background: Thoracoscopic esophagectomy (TE) as minimally invasive esophagectomy for thoracic esophageal cancer has become widely prevalent around the world over the past decade. However, results from a large-scale, multicenter randomized controlled trial that compared long-term survival as the primary endpoint between TE and conventional open transthoracic esophagectomy (OE) have not yet been demonstrated. We conducted a multicenter randomized phase III study (JCOG1409) to confirm the non-inferiority of TE to OE in terms of overall survival (OS) for thoracic esophageal cancer (UMIN000017628). Methods: Eligible patients with clinical stage I-III, excluding T4, thoracic esophageal squamous cell carcinoma were randomized to undergo either OE or TE. The primary endpoint was OS, with secondary endpoints including relapse-free survival (RFS), the proportion of patients achieving R0 resection, the proportion of patients needing conversion from TE to OE, adverse events, the proportion of patients requiring re-operation, changes in postoperative respiratory dysfunction, and postoperative quality-of-life score. Non-inferiority would be confirmed if the upper limit of the confidence interval (CI) for the hazard ratio (HR) does not exceed 1. Here we compare between-treatment differences in quality-adjusted survival using a Q-TWiST analysis in all randomized pts (29-month minimum follow-up). Methods: Survival time was partitioned into 3 health states: toxicity (TOX), time without symptoms of disease progression or toxicity (TWiST), and relapse (REL). TOX was defined as time spent with all-cause grade 3/4 adverse events after randomization, prior to disease progression.

TWiST was defined as time prior to REL where pts did not experience TOX. REL was defined as time between disease progression and death, or the last known date alive. Mean duration of time in each state was calculated for each treatment group using descriptive statistics and Kaplan-Meier analysis. Utility values from the 3-level EQ-5D (EQ-5D-3L) questionnaire were used to adjust the time spent within each health state for QoL and to calculate Q-TWiST as the utility-weighted sum of the mean health state durations. Bootstrapping (500 samples) was used to estimate time in each health state and to compare mean Q-TWiST estimates between treatments. A betweengroup difference in Q-TWiST of 5 weeks was prespecified as being clinically important (defined as 10% of OS; based on a median OS in CT group of 10.7 months). Sensitivity analyses were conducted using different combinations of prespecified utility weights for each health state.

Results: 970 pts were randomized 1:1:1 to N+I (n = 325), N+CT (n = 321), or CT (n = 324) and included in the Q-TWiST analysis. Median duration of follow-up for survivors was 155 weeks. Mean time in each health state was significantly longer for pts treated with N+I or N+CT compared to CT (Table ). Between-group differences in Q-TWiST score were considered clinically important: 5.7 weeks (95% CI 5.5-6.0) favoring N+I vs CT and 7.6 weeks (95% CI 7.4-7.9) favoring N+CT vs CT. Sensitivity analyses supported these findings. Conclusions: In CheckMate 648, pts with unresectable advanced ESCC treated with N+I or N+CT had significantly longer OS compared with those treated with CT. Quality-adjusted survival using Q-TWiST also significantly favored N+I and N+CT compared to CT alone. Pts treated with N+I and N+CT not only experienced increased survival time, but also better QoL during their survival time. Clinical trial information: NCT03143153. Research Sponsor: Bristol Myers Squibb (Princeton, NJ, USA).

Mean (95% CI), weeks ) , resulting in approvals in many countries. We present first comprehensive exploratory biomarker analysis results from this trial. Methods: Whole exome sequencing (WES) of baseline tumor tissue and matching blood was performed to assess tumor mutational burden (TMB) and select gene alterations. TMB-high tumors were defined as $ 199 mutations/exome. RNA sequencing of baseline tumor tissue was used to assess gene expression signatures (GES). GES subgroups were defined by signature score tertiles.

N+I (n = 322) N+CT (n = 310) CT (n = 303) Q-TWiST

Results: In total, 60% (191/321) of patients receiving NIVO + chemo were both WES-and GESevaluable; 62% (200/325) and 58% (188/325) of patients receiving NIVO + IPI and 59% (190/324) and 59% (192/324) receiving chemo were WES-and GES-evaluable, respectively. In the NIVO + chemo arm, patients with TMB-high tumors had numerically longer median OS (mOS) compared with TMB-low tumors, whereas mOS was similar between TMB subgroups treated with NIVO + IPI, although the number of patients with TMB-high tumors was small (Table ). Higher inflammation and lower b-catenin GES scores were associated with improved OS benefit of NIVO + chemo or IPI vs chemo (Table ). Lower fibroblast GES scores were associated with improved OS benefit of NIVO + IPI vs chemo (Table ).

Additional biomarker analyses, including select gene alterations and GES in tumor cell PD-L1 subgroups, will be presented. (2016) (2017) (2018) (2019) (2020) was queried to identify all solid (breast, prostate, lung, gastrointestinal, renal and thyroid) cancer patients admitted with spinal cord compression. Multivariate logistic regression was used to evaluate differences in socio-demographics, medical comorbidities and outcomes between MESCC in gastric cancer patients and those with other solid cancers. The primary outcome included inpatient mortality, length of stay (LOS), and total hospital charges (THC). Results: 78,385 patients with the above solid cancers were admitted for spinal cord compression. Among them, 710 had gastric cancer. Patients with gastric cancer were younger (Mean age: 59.1 vs 66.3 years, p , 0.001). They had higher prevalence of anemia (56 vs 41%), protein energy malnutrition (28.9 vs 18.9%, p , 0.001), and lower prevalence of COPD (8.45 vs 18.5%, p =0.003), smoking (22.5 vs 33.6%, p =0.007) and CKD (9.4 vs 12.3%, p =0.03). On multivariate regression, those with GC-MESCC had two-fold higher odds of all-cause mortality (adjusted odds ratio (aOR): 2.0; 95% CI: 1.05-3.96, p = 0.034). On subgroup analysis, mortality was about four times higher for females with GC-MESCC relative to the other group (aOR = 3.8, 95% CI: 1.69-8.52, p = 0.001). There was a trend towards increased LOS (8.9 vs 7.8 days) and THC ($115, 805 vs $96, 074) but it was not statistically significant. Compared with the other cohort, GC-MESCC patients had higher rates of blood transfusion (16.2 vs 9%, p = 0.003). Conclusions: Metastatic epidural spinal cord compression is associated with increased odds of inpatient mortality in gastric cancer patients compared to those with other solid malignancies. Hence, these patients ought to have urgent intervention and close monitoring to prevent adverse outcomes. Research Sponsor: None. compared to those with private insurance 31 weeks (20-47) p,0.001. Multivariate analysis revealed that any treatment, insurance status, and lower income were all predictors of survival. Treated Hispanics demonstrated no difference in survival then their treated non-Hispanic counterparts (median survival 18.5 vs 18.7 months) with overall 5 year survival at 24% and 25% respectively (p=0.66). Conclusions: Despite lower prevalence, there is a disproportionately higher number of metastatic and untreated cases of esophageal cancer among Hispanics. This disparity may be explained by Hispanics' limited access to medical care exacerbated by their socioeconomic and insurance status.

Our findings warrant further clinical and epidemiologic research to reveal other factors impacting these health and health care disparities. Research Sponsor: None.

259 Poster Session

Reliability of computed tomography to determine the eligibility of conversion surgery for gastric cancer with para-aortic lymph node metastasis. First Author: Takeyuki Wada, Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan Background: Although gastric cancer (GC) with para-aortic lymph node (PAN) metastasis is diagnosed as stage IV and basically treated with chemotherapy, it can be the candidate of conversion surgery when PAN metastasis was limited in localized area as oligometastatic status. Recently, we reported that pathological complete response at PAN (pCR at PAN) after chemotherapy was a good surrogate marker in conversion surgery for GC with PAN metastasis. However, it is difficult to predict pCR at PAN before surgery. Computed tomography (CT) is a standard procedure for clinical diagnosis of lymph node metastasis in GC.This study aimed to evaluate the reliability of CT to predict pCR at PAN after chemotherapy. Methods: The study examined patients who received radical gastrectomy with D2 and PAN dissection after chemotherapy for gastric cancer with PAN metastasis (#16a2/b1) from 2004 to 2020. PAN greater than 10mm in long axis was diagnosed as clinically positive. Patients were classified into 2 groups as pPAN-CR and pPAN-nonCR according to the pathological diagnosis of PAN. Accuracy, sensitivity, specificity, positive predictive value, and negative predictive values for PAN diagnosis were retrospectively investigated. Moreover, the relationship between shrinkage ratio at PAN and pathological diagnosis was also investigated. Results: A total of 46 patients were examined in the present study. The number of pPAN-CR and pPAN-nonCR patients were 31 and 15, respectively. 5-year overall survival rate was 76% in pPAN-CR and 0% in pPAN-nonCR patients. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of PAN were 52.2%, 60.0%, 48.4%, 36.0%, and 28.6%, respectively. Median shrinkage ratio of PAN was 38% (-20%-88%) in pPAN-CR and 40% (-20%-75%) in pPAN-nonCR patients. There was no statistically significant relationship between shrinkage ratio and pathological diagnosis of PAN (p=0.655). Conclusions: CT diagnosis for PAN after chemotherapy was not reliable. The indication of conversion surgery for GC with PAN metastasis should not be determined based on the size and shrinkage of PAN. Research Sponsor: None.

Metachronous remnant gastric cancer after proximal gastrectomy. First Author: Kenichi Ishizu, Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan Background: Proximal gastrectomy is frequently selected for early gastric cancer located at the upper third of the stomach. Annual postoperative endoscopy is considered to be useful for the early detection of metachronous remnant gastric cancer (MRGC). Despite that, we sometimes have also encountered cases that are not suitable for endoscopic resection (ER). The aim of this study is to identify the risk factors for the patients who developed MRGC after proximal gastrectomy, received annual endoscopy, but are not eligible for ER (non-ER). Methods: We retrospectively analyzed 191 patients who had received annual endoscopic surveillance after undergoing PG for cT1 gastric cancer at NCCH between 2006-2015. MRGCs were categorized into two groups: ER group and non-ER group. The remnant stomach was defined as three locations: pseudofornix (PF), corpus and antrum. Results: The median observation period was 73 (range 12-168) months. MRGC was observed in 29 cases with 32 lesions. ER was eligible for 20 lesions (ER group, 62.5%), but 12 were not (non-ER group, 37.5%). We compared the characteristics between of ER group and non-ER group in terms of sex, age (.65 years), interval from the initial surgery (.60months), the location (PF vs non-PF), and crosssectional circumference (posterior wall vs. others). In both univariate and multivariate logistic regression analysis, only the location at PF was identified as a risk factor for non-ER group (OR 25.0, 95% CI: 1.8-339, p = 0.015). Among 12 lesions of the non-ER group, the location of PF was found in 6 (50%) lesions. As compared with MRGC at the non-PF, that at the PF (n = 6) was characterized by younger patients (57.5 (range 37-69) years vs. 69 (56-77) years), larger size (36 (7-57) mm vs. 9 (9-24) mm), deeper depth (MP or deeper; 5/6 vs. 0/6), more frequent undifferentiated-type histology (4/6 vs. 0/6) and frequent nodal metastasis (3/6 vs. 0/6). The interval to detect MRGC appears to be longer in the months than that of the non-PF (60 (31-96) months), but the difference was not statistically significant (p = 0.86). Then, we examined the visibility and the mucosal normality of the area developing MRGC in the annual follow-up endoscopy one year before the detection of MRGC (n =32). In 25 lesions at the non-PF, the visibility and the mucosal normality was secured in 21 (84%). while 5 PF lesions were difficult to observe (71.4%, p = 0.01) due to food residues in 4 (57%, p = 0.047) and insufficient expansion of the gastric mucosa in 4 (57%, p = 0.001).

Conclusions: Detection of the MRGC at the PF at an early stage is crucial and challenging. With annual follow-up endoscopy, complete clearance and adequately extending the gastric mucosa could lead to the early detection of MRGC at the PF.

261 Poster Session

Unveiling proteomic diversity: A quantitative study of antibody drug conjugate and chemotherapy targets in gastroesophageal cancer. First Author: Sheeno P. Thyparambil, mProbe Inc., Rockville, MD Background: Gastroesophageal cancer (GEC), is a significant global health concern with a 5-year relative survival of 7% for metastatic GEC. Standard treatments often include surgery, chemotherapy, and radiation therapy, but their effectiveness can be limited. Chemotherapy is frequently utilized in the treatment of GEC, although no biomarkers for chemotherapy are used in the selection of the chemo agent. There are several well-known biomarkers of resistance and sensitivity for various chemo agents. We used targeted proteomics to quantify protein expression levels of several protein biomarkers associated with chemotherapy efficiency in 125 GEC patients. These include resistance markers for platinum agents (ERCC1), and tubulin inhibitors (TUBB3). It also includes sensitivity markers for irinotecan/topotecan (Topo1), and doxorubicin/ etoposide (Topo2A). We also assessed the protein levels of several antibodies-drug conjugate markers (EGFR, Her2, Trop2, FR-alpha, Mesothelin, Axl, CLDN18.2, and Nectin-4). Methods: FFPE tumor tissues from 125 clinical GC patients were microdissected and solubilized for mass spectrometry-based targeted proteomic analysis in our CLIAcertified laboratory. 72 proteins were quantified from 2-3 sections of FFPE tissue.

Results: 5-Fluorouracil (5-FU), taxanes, and platinum agents (such as carboplatin) are among the chemotherapy agents that are frequently used to treat GEC. TYMP, a sensitivity marker for 5-FU, was expressed in 32% of GEC cases. ERCC1, a resistance marker for platinum drugs, was expressed at 34%. Additionally, 48% of GEC exhibited TUBB3, a resistance marker for paclitaxel and docetaxel. Topoisomerase 1 (Topo1) is the target for irinotecan or topotecan, and is also the target for some ADCs (e.g. trastuzumab deruxtecan, sacituzumab govitecan etc.). Topo1 was expressed in 92% of GEC with a 10x range (415 -4195 amol/mg). Another topoisomerase, Topo2A, targetable by etoposide, epirubicin, and doxorubicin, was expressed in 59% of GEC with 19x range (402-7804 amol/mg). ADC targets, such as EGFR (82% detected with 184x range of distribution), Her3 (18%, 4x), AXL (18%,7x), MET (27%, 19x) , and Trop2 (50%, 57x) showed a wide range of protein expression. With a 56x range (318 -17786 amol/mg), Her2 was found in 46% of GEC, of which 12% of GEC had overexpression of Her2 (.740 amol/mg), suggesting that the majority of GEC has low levels of Her2 (318-690 amol/ mg), which is potentially targetable by newer anti-Her2 agents. Conclusions: Every cancer is different, and the ability to quantitate simultaneously 72 protein biomarkers from 2-3 FFPE sections provides a wealth of actionable information that, when combined with other multi-omics biomarker data, will help guide clinical treatment or patient stratification for clinical trials. Research Sponsor: None.

262 Poster Session

Natural history of gastric leiomyoma. First Author: Kwangbeom Park, Nowon Eulji Medical Center, Seoul, South Korea Background: Most gastric leiomyomas are asymptomatic and benign subepithelial tumors (SETs); however, some may increase in size or become symptomatic. Understanding their natural history is therefore important to their management. We investigated the natural history of histologically proven gastric leiomyomas. Methods: We retrospectively reviewed histologically proven gastric leiomyoma cases at a tertiary center. The baseline characteristics of these cases were analyzed, and those with a follow-up period of at least 12 months without immediate resection were evaluated. The primary outcome was the frequency of size increase of more than 25% during the followup period, and the secondary outcome was the histopathologic results in cases that underwent resection. Results: Among the 231 patients with histologically proven gastric leiomyomas, the most frequent location was the cardia (77.1%), and the median size was 3 cm (IQR 2-4 cm). Eighty-four cases were followed up over a median period of 50.8 months (IQR 27.2-91.3 months). During the follow-up period, tumor size increased in two cases (2.4%). Surgical results showed that one case was leiomyoma, and the other was leiomyosarcoma. Among the remaining cases without change in size, 15 underwent surgical resection (n = 10) or endoscopic resection (n = 5), and all cases were confirmed as leiomyoma. Conclusions: Most gastric leiomyomas are benign SETs, and an increase in size is not frequent, even in large-sized cases. Close monitoring with routine follow-up without resection may be sufficient in cases of histologically proven gastric leiomyoma. However, in cases of ulceration or size increase, resection may be beneficial. Research Sponsor: None.

263 Poster Session

Prediction of lymph node status in stage T1 esophageal squamous cell carcinoma. First Author: Yongshun Chen, Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China Background: With the development of endoscopic therapy and the introduction of immunotherapies, it is more important for preserving the esophagus and uninvaded lymph nodes to avoid the damages involving the long-term quality of life and normal immune function caused by esophagectomy with radical lymphadenectomy. Methods: We collected patients with T1 ESCC who underwent endoscopic resection or esophagectomy from 2014 to 2021 in three cancer centers. The primary end point was presence of lymph node metastasis (LNM) in surgical resection specimens or detection of metastases during followup. Univariate and multivariate logistic regression were used to screen the clinicopathological features related to LNM. Using the function 'lrm' constructed the prediction model. The area under the curve (AUC) of receiver operating characteristic and calibration graphs were used to assess the performance of the model. An external validation was conducted to evaluate the generalization of the model. We then prospectively collected 28 surgically resected tissue samples of T1 ESCC to further supplement the model from the cellular and molecular level, and used 6 markers (CK, CD34, D2-40, CD4, CD8, FOXP3) and DAPI dye to process multiple immunofluorescence (mIF) staining. Afterwards, we analyzed the density, spatial distribution of microvessels, lymphatic capillaries and tumor-associated immune cells and the interaction between them and malignant cells in the tumor microenvironment of T1 ESCC to explore the relationship between tumor microenvironment and risk of LNM.

Results: 1109 patients with T1 ESCC were included. 653 patients from two centers constituted the training cohort, and 456 patients from the third center served as the validation cohort. Multivariate logistic regression based on the training cohort showed that tumor invasion into the submucosa, poor histological grade, and lymphovascular invasion were risk factors for LNM in T1 ESCC. Subsequently, we constructed a model based on three variables to predict the risk of LNM in T1 ESCC. The model demonstrated good discriminative ability (AUC 0.858, 95%CI 0.826-0.890). After mIF staining of 28 prospectively collected T1 ESCC tissue samples, we observed that microvessels and lymphatic capillaries were abundant in the mucosa in lymph node-positive samples but not in lymph nodenegative samples. In addition, the average density of FOXP3 + T cells in samples with and without metastasis was 253/mm 2 and 26/mm 2 (P , 0.001), and the average density of CD8 + T cells was 112/mm 2 and 432/mm 2 (P , 0.001) in quantitative analysis, respectively.

Conclusions: This study (RENMIN-237) developed a well-performing LNM risk stratification model of T1 ESCC to reduce both overtreatment and undertreatment, and we found that FOXP3 + T cells in the tumor microenvironment are a risk factor for LNM, while CD8+ T cells can serve as a protective factor against LNM. Research Sponsor: None.

Development and application of an ultra-sensitive ctDNA mutation profiling assay in monitoring therapy response and drug resistance. First Author: Tom Zhang, Predicine, Inc., Hayward, CA Background: Next-generation sequencing (NGS) assays offer efficient high-throughput profiling methods for analyzing circulating tumor DNA (ctDNA) in blood or other liquid biopsy specimens. The ctDNA mutant allele fractions of patients after treatment is often very low and below the detection limit of regular cfDNA assays. Here we report the development and clinical application of a CLIA-certified ultra-sensitive NGS cfDNA assay in detecting the low-frequency ctDNA mutations and monitoring therapy response and drug resistance in patients with metastatic gastroesophageal adenocarcinoma under combined blockade treatments. Methods: PredicineCARE ULTRA cfDNA assay with 100,000X sequencing depth was validated under CLIA settings. Limit of blank (LoB) and limit of detection (LoD) were established by profiling 38 healthy donor plasma samples, 23 contrived human cfDNAs samples from patients with various cancers, and 30 replicates of well-established ctDNA reference standards. In silico down-sampling of FASTQ files was carried out to test the sensitivity of this assay with a lower coverage (50,000X). This assay was then adopted for longitudinal sequencing of 57 serial plasmas from 6 patients with HER2+ gastroesophageal adenocarcinomas (GEC) who underwent combined treatments (capecitabine, oxaliplatin, bevacizumab and trastuzumab) at different time points (baseline, response, and progression

266 Poster Session

A scoring system for selecting nivolumab or irinotecan in the later-line chemotherapy for advanced gastric cancer: A Japanese multicenter retrospective study. First Author: Yusuke Amanuma, Department of Clinical Trial Promotion, Chiba Cancer Center, Chiba, Japan Background: Although Nivolumab (NIVO) or Irinotecan (IRI) monotherapy is one of the later-line chemotherapies for the advanced gastric cancer (AGC) patients, there are no prospective data of their comparison, and no indicators for selection of them. Methods: Clinical data of AGC patients treated with NIVO or IRI as later-line were collected from 7 institutions between September 2015 and September 2018. Efficacy of the two treatment groups was compared in the entire cohort and in the propensity score matching cohort. Factors which affect the prognosis were explored by multivariate analyses and the scoring system was developed using Cox regression. Results: In the analysis of entire cohort (317 patients), the median OS was 4.8 months (95% CI: 3.6-5.8) in the NIVO group and 5.9 months (95% CI: 4.9-7.2) in the IRI group, and those were 4.8 months (95% CI: 3.6-5.7) and 6.0 months (95% CI: 4.5-7.2) in the analysis of the propensity score matching cohort (248 patients), respectively. There were no differences in OS. We developed a risk score involving 1-Neutrophil to Lymphocyte Ratio (NLR), 2age, 3-ECOG performance status, 4-peritoneal metastasis, 5-gastrectomy, and 6-liver metastasis to assess potential effect modification. Based on the result, IRI was favored in the higher-risk group ($4 points, with double weight to 2, 3, and 4) for both OS/PFS. In contrast, NIVO was better OS/PFS in the lower-risk group (,1 point).

Conclusions: According to the real-world data from multicenter in Japan, NIVO and IRI generally showed equivalent outcomes. The scoring system we explored may be useful for selecting appropriate later-line chemotherapy, either NIVO or IRI. Research Sponsor: None.

267 Poster Session

Real-world comparison of treatment outcomes between advanced esophagogastric junction adenocarcinoma and gastric adenocarcinoma. First Author: Toru Kadono, Cancer Chemotherapy Center, Osaka Medical and Pharmaceutical University, Taktasuki, Osaka, Japan Background: The characteristics of esophagogastric junction adenocarcinoma (EGJA) differ from those of gastric adenocarcinoma (GA). Although chemotherapy for advanced GA has been adapted for advanced EGJA, its efficacy remains unknown. This study aims to elucidate the effectiveness of chemotherapy for advanced EGJA in real-world practice. Methods: This retrospective study compared treatment outcomes between advanced GA and EGJA in patients with performance status (PS) 0 to 2 who received doublet or triplet chemotherapy, including platinum agents, as first-line treatment at our hospital between 2010 and 2020. Treatment-related adverse events (TRAEs) occurred in 27 patients (82%), with pruritus (n = 13, 39%), rash (n = 7, 21%), hypothyroidism (n=7, 21%), xerosis (n = 6, 18%), diarrhea (n = 5, 15%), hypopituitarism (n = 5, 15%), pneumonitis (n = 1, 3%), and hepatic dysfunction (n = 1, 3%). Among these TRAEs, one patient developed grade 3 of hepatic dysfunction, which resolved with corticosteroid. TRAEs which led to discontinuation of nivolumab were hepatic dysfunction (n = 1, 3%), diarrhea (n = 1, 3%), and pneumonitis (n = 1, 3%). No treatment-related death was observed. With a median follow-up of 10.3 months, 1-year DFS rate was 63.3% (95% CI, 39.8-79.7%). Among 9 patients who experienced recurrence (locoregional; n = 3, distant; n = 6), 8 patients received subsequent therapy, including systemic chemotherapy (n = 5) and salvage chemoradiotherapy (n = 3).

The safety and short-term efficacy of adjuvant nivolumab after neoadjuvant DCF and surgery was comparable to the results of the CheckMate-577 trial. Our study suggests that adjuvant nivolumab might be a possible treatment option in patients with locally advanced ESCC patients with residual pathological disease after neoadjuvant DCF followed by surgery. Research Sponsor: None.

273 Poster Session

Real-world experience with trastuzumab deruxtecan among patients with gastric cancer: 4 month-interim analysis of an all-patient post-marketing surveillance study in Japan. First Author: Hisato Kawakami, Kindai University Faculty of Medicine, Osaka-Sayama, Japan Background: Interstitial lung disease (ILD) is an important identified risk in the Japanese risk management plan of trastuzumab deruxtecan (T-DXd). In Japan, all-patient post-marketing surveillance (PMS) is underway to investigate the risk of ILD among patients with gastric cancer treated with T-DXd in a real-world setting. We present an interim analysis of the large-scale all-patient PMS. Methods: This is an observational, multicenter, all-patient PMS (jRCT2001200001) with an observation period of 12 months that enrolled all patients treated with T-DXd for HER2-positive unresectable advanced or recurrent gastric cancer between Sep 2020 and Dec 2021. This interim analysis is based on safety data from the first 4 months of all enrolled patients. All potential ILD (identified based on the pre-specified list of AE terms) reported by physicians were adjudicated by an independent ILD adjudication committee (ILD-AC).

Results: 1799 patients were included in our study (Table ). We distinguished localized from metastatic cases based on specific drugs administered or not administered during the followup period (i.e. biologics). For the entire cohort, the median number of PETCTs performed per patient over the study period was 3. 364 (20.2%) patients underwent a single PETCT, 946 (52.6%) patients underwent $2 PETCTs, and 25 patients underwent $ 10 PETCTs. Assuming a single PETCT is considered "guideline concordant" during diagnosis and treatment of localized CRC, 52.6% (946/1799) of patients in our cohort underwent "guideline discordant" PETCT scans. Conclusions: Despite professional guidelines recommending against routine PETCT to monitor for recurrence following curative-intent treatment of CRC, there remains a large volume of "guideline-discordant" PETCTs in this space. Professional guidelines such as "Choosing Wisely" have largely failed to prevent this example of healthcare overuse. Research Sponsor: None.

Patient characteristics.

Characteristic

218 Poster Session

The TGF-beta pathway alterations in young-onset colorectal cancer. First Author: Deniz Can Guven, Hacettepe University Cancer Institute, Ankara, Turkey Background: Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer-related deaths worldwide. The epidemiological evidence suggests an increased incidence of young-onset CRC, defined as the CRC in individuals 50 years old or younger. The TGF-beta alterations are among the pivotal events in the CRC carcinogenesis. However, the rate of mutations leading to TGF-beta alterations are yet to be defined in young-onset CRC. Therefore, we conducted a bioinformatics analysis of the mutations associated with TGF-pathway alterations according to age (#50 years of age vs. .50 years) and primary tumor location (colon vs. rectum). Methods: We used published genomic data of 6286 patients with CRC from the 16 CRC datasets included in the cBioPortal database. The presence of mutations in the following genes was used to define TGF-beta alterations: TGFBR2, TGFB2, TGFBRAP1, TGFBR1, TGFBR3, TGFB1I1, TGFBI, TGFB1, TGFBR3L, TGFB3, TGFA, SMAD1-9, BMPR2, BMPER, BMP3, BMP2K, BMP1, BMP5, BMP10, BMPR1A, BMP15, BMP7, BMP23, BMP4, BMP6, BMPR1B, BMP8B, BMP8A. The presence of TGF-beta alterations according to the age (#50 years of age vs. .50 years) were evaluated with Chi-square tests. The association between primary tumor distribution (colon vs. rectal) and age were evaluated across patients with and without TGF-beta pathway alterations. The effect of WNT pathway alterations on the overall survival and survival after the metastatic stage was evaluated with Kaplan-Meier survival curves. A type-I error level of 5% (p,0.05) was considered the threshold limit for statistical significance. Results: A total of 2280 patients with available age data was included in the analyses.The mutations associated with TGF-beta pathway alterations was more common .50 years of age compared to #50 years of age. (28% vs. 17.4%, p,0.001). Additionally, mutations associated with TGF-beta pathway alterations were more frequent in colon cancer compared to rectum (25.4% vs. 18.7, p,0.001). While progression-free survival was higher in patients with mutations associated with TGFbeta pathway alterations (12.5 vs. 10.7 months, p=0.012), the overall survival (59.6 vs. 58.9 months, p=0.896) and survival after metastatic stage (49.7 vs. 56.5 months, p=0.109) were similar across two groups. Conclusions: In this study, we observed a higher rate of mutations associated with TGF-beta pathway alterations in older CRC patients compared to patients with young-onset CRC. Furthermore, the mutations associated with TGF-beta pathway alterations were more frequent in colon primaries.

The overall survival was independent of these mutations. Further research is required to delineate the association between TGF-beta pathway alterations and onset of CRC, as well as the CRC prognosis. Research Sponsor: None.

219 Poster Session

Application of GPT-4 foundation model for risk prediction and stratification in colorectal cancer. First Author: Antonio Rueda-Lara, Medical Oncology Department, Hospital Universitario La Paz, Madrid, Spain

Background: Deep Learning Language Models (LLMs) show significant potential in analyzing complex data, particularly in oncology, where they can predict and stratify patient risks, detect non-linear interactions, and weigh multiple variables. This study applies LLMs to stage II/III localized colon cancer patients to assess their effectiveness in identifying risk subgroups. Methods: In this retrospective study, we examined a cohort of stage II and III localized colorectal cancer patients diagnosed from September 2016 to December 2022 at La Paz University Hospital. Utilizing the GPT-4 API beta version, patients were stratified into high and low-risk groups for relapse based on various risk parameters outlined in the table. Notably, adjuvant treatment data was excluded from the input. The model was prompted with the question, "Given the following risk parameters for localized colorectal cancer {param}, guess whether the patient is in low risk or high risk for relapse," and the model provided dichotomic responses categorized as either 1 (high risk) or 0 (low risk). Results: Patient characteristics are depicted in the table. During a median follow-up of 23.68 months, 63 recurrence events and 73 deaths were observed. The GPT-4 model stratified patients into low (37.9%) and high-risk (62.1%) groups, with the survival curves showing a significant difference in outcomes between the groups. Low-risk patients had a relapse-free rate of 93% at 36 months vs 63% in the high-risk group. In univariate analysis, the high-risk variable had a hazard ratio (HR) of 4.26 (95% CI: 2.03-8.95; p , 0.005). When stratified by adjuvant treatment, no significant difference in relapse probability was observed for those receiving therapy. However, without adjuvant therapy, high-risk patients had an HR of 12.41 (95% CI: 3.72-41.97; p , 0.005) for relapse. Conclusions: GPT-4 demonstrated its potential in predicting oncology outcomes by accurately understanding colorectal cancer risk factors. To fully harness the benefits of LLMs in the future of oncology, they must be fine-tuned on extensive oncological datasets to improve patient risk stratification and treatment selection, ultimately leading to better patient outcomes. Research Sponsor: None.

220 Poster Session

Comparison of palliative treatment modalities among patients with colon cancer: A review of NCDB Database. First Author: Baqir Jafry, UT Southwestern Medical Center, Dallas, TX Background: Among colon cancer patients some patients present with significant symptom burden needing upfront palliation-directed therapies, aimed to improve the quality of life of patients with severe illnesses. These include palliation-directed surgery, chemotherapy, radiation, pain management, or a combination of these. The extent to which these palliation-directed therapies are utilized in colon cancer remains under-explored. This study's purpose was to understand the trends in utilization and factors associated with palliation-directed treatment modalities among patients with colon cancer. Methods: From the National Cancer Database, we identified patients with colon cancer who received first-line palliation-directed therapies from 2004 to 2016 without an intent to give definitive therapy. We evaluated the use of these treatments over time and compared frequencies of categorical variables using Chi square tests. A multivariate logistic regression was also used to evaluate patient characteristics associated with the use of these treatments. Results: We identified a total of 21,516 patients receiving palliation-directed therapy among patients with colon cancer -19,506 received single palliation-directed therapy, 908 received a combination of palliation-directed treatments without pain management and 1102 received a combination of palliation-directed treatments with pain management. Of the 21,516 patients who received single palliation-directed treatments, 50.6% and 49.4% were male and female, respectively. The mean age was 67 years. Most patients had no existing comorbidities (68.7%), lived in metropolitan areas (81.6%), had grade 2 (59.4%) and AJCC Clinical stage 4 colon cancer (32.6%). Overall, most patients received chemotherapy (50.7%) as a palliative treatment, followed by surgery (25.2%), pain management (14.4%) and radiation (9.7%). The utilization of chemotherapy (39.6% in 2004 to 63.1% in 2016) and pain management (9.7% in 2004 to 12.7% in 2016) increased over time while the utilization of surgery (37.1% in 2004 to 16.9% in 2016), and radiation (13.6% in 2004 to 7.3% in 2016) decreased over time. The type of facility, readmission rates, and proportion of individuals who were whites, elder (age.50), resided in metropolitan areas and had insurance were significantly different between groups. Male patients, patients without existing comorbidities, and patients with grade 2 tumors had higher odds of receiving surgery, radiation, or chemotherapy as palliative therapy compared to pain management. Conclusions: Utilization of first-line palliation-directed chemotherapy has increased significantly from 2004 to 2016 whereas surgery and radiation therapy use has decreased in that period. Notably, patient characteristics such as gender, absence of existing comorbidities and grade 2 tumors influence the choice of therapy. Research Sponsor: None.

Trends in utilization of MSI testing and reporting among patients with gastrointestinal cancers: A review of NCDB Database. First Author: Baqir Jafry, UT Southwestern Medical Center, Dallas, TX Background: MSI-H tumors have a different disease biology and clinical outcomes compared to MSS/MSI-low tumors. The frequency and pattern for MSI testing and reporting is unknown. The aim of this study was to characterize the trends of MSI testing and reporting among GI cancers. Methods: From the National Cancer Database, we identified all GI cancer patients from 2010 to 2016 to determine the number of patients where MSS/MSI low or MSI-H data were available. We describe the basic tumor and disease characteristics and treatment utilization for the two groups. Results: Between 2010-2016, MSI testing was done in 140,602 patients in colon, small intestine and rectal cancers among all GI cancers. MSI testing increased significantly during this study period (11,400 in 2010; 15,021 in 2011; 17,968 in 2012; 20,810 in 2013; 21,973 in 2014; 25,012 in 2015; 28,418 in 2016) . We identified a total of 120,349 patients with MSI status reported, among these three tumor types, most commonly among colon followed by rectal and then small intestinal cancers.

TPS223 Trials in Progress Poster Session

Combination of hSTC810 and capecitabine therapy in metastatic colorectal cancer with resistance or intolerance to oxaliplatin and irinotecan-based chemotherapy: A single arm, phase 1b/2, multicenter study. First Author: Jiwon Lee, Korea University Hospital, Seoul, South Korea Background: hSTC810 is a humanized anti-BTN1A1 monoclonal antibody of the IgG4 isotype that binds to human BTN1A1 and blocks the interaction between BTN1A1 and its ligands. Butyrophilin 1A1 (BTN1A1) is a novel immune checkpoint protein that exhibits an expression pattern mutually exclusive to that of PD-1/PD-L1. BTN1A1 has been shown to inhibit anti-CD3-induced cytokine production and T-cell proliferation and also inhibit anti-CD3-induced p38 mitogen-activated protein kinase (MAPK), cAMP response element-binding protein (CREB) and target of rapamycin (TOR) phosphorylation in human T-cells. Mouse studies demonstrated that an anti-BTN1A1 antibody exhibited antitumor activity both as a single agent and in combination with anti-PD-1/PD-L1 or radiation therapy. In the first in human phase 1 study, investigating the safety and efficacy of hSTC810 in solid tumors, hSTC810 showed acceptable safety profile and the disease control rate (DCR) was 39.3%, which indicates its potential efficacy. Methods: This multi-center, open label phase 1b/2 study evaluates the safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of hSTC810 combined with capecitabine in patients with metastasis/recurrent colorectal cancer. The trial is enrolling adults who are (1) histologically or cytologically confirmed colorectal adenocarcinoma (2) resistant or intolerant to oxaliplatin and irinotecan-based chemotherapy (3) adequate hematologic, hepatic, renal function (4) measurable or nonmeasurable disease by RECIST 1.1 (5) ECOG PS 0~2 (6) resolved acute effects of any prior therapy. Treatment will continue until disease progression or unacceptable toxicity, whichever occurs first. The primary endpoint of phase 1b is to determine dose-limiting toxicity (DLT), and recommended phase 2 dose (RP2D) of hSTC810 combined with capecitabine, each in 21-day cycles. Phase 1 comprises 3 escalation arms, and if the initial dose is deemed unsafe, 2 deescalation arms will be initiated. Once the RP2D is determined, the Phase 2 will enroll up to 39 patients. The primary endpoint of phase 2 is progression free survival (PFS); secondary endpoints include objective response rate, overall survival, disease control rate, duration of response and quality of life. The study began in Q4 2023 and is recruiting patients. AEs are assessed according to CTCAE v5.

Tumor response is determined according to RECIST 1.1 criteria. An exploratory study is underway to investigate the impact of hSTC810 on the tumor microenvironment and cytokines, utilizing both tissue biopsies and blood sampling. Clinical trial information: NCT05990543. Research Sponsor: STCube.

TPS224 Trials in Progress Poster Session

BXQ-350: A phase 1b/2 placebo controlled, double blinded study on the efficacy and safety of BXQ-350 in combination with mFOLFOX7 and bevacizumab in newly diagnosed metastatic colorectal carcinoma (mCRC). First Author: Reema Anil Patel, University of Kentucky, Lexington, KY Background: Ceramides and sphingosine-1-phosphate (S1P) are key bioactive signaling molecules. Ceramides are proapoptotic and mitigate chemoresistance. Conversely, S1P promotes cancer cell proliferation, activates multiple oncogenic pathways, and stimulates immuno-suppressor cell populations promoting a pro-tumoral microenvironment. Several studies in colorectal cancer patients have shown high levels of ceramides are associated with improved survival, while high S1P levels are associated with a poor prognosis. Hence, modulation of sphingolipid metabolism could be a promising therapeutic approach. BXQ-350 is a nanovesicle of Saposin C, an allosteric activator of sphingolipid metabolism, that lowers systemic S1P and increases C18 ceramide. BXQ-350 was investigated in a Phase 1 dose-escalation safety study in an cancer patients with advanced solid malignancies (NCT02859857). BXQ-350 was safe and well-tolerated (no DLT, no MTD). Also, 13 patients (~17.8% of evaluable patients) had a clinical benefit up to cycle 6 and beyond (PR, SD). Among patients with PFS . 6 months, there were 4 recurrent CRC patients: 1 patient had a PFS of ~12 months, 2 of ~18 months, and 1 is still on study after 6 years. Furthermore, there were signs that BXQ-350 may alleviate symptoms of CIPN as 4 out of 10 patients with chronic CIPN at time of enrollment experienced an improvement of their symptoms. Methods: BXQ-350 is being investigated in a Phase 1b/2 study in combination with mFOLFOX7 and Bevacizumab in newly diagnosed mCRC patients (NCT05322590) to assess the efficacy and safety of BXQ-350. Design of the Phase 1b (open label study): A safety dose escalation part to establish the RP2D: patients will initially receive 1.8 mg/kg BXQ-350 in combination with mFOLFOX7 and Bevacizumab. If safe (no MTD), dose of BXQ-350 will be increased to 2.4 mg/kg and 9 additional patients will be entered at this dose level. If safe, then this dose will be the RP2D and 21 additional patients will be enrolled, completing a 30 patient expansion cohort; Efficacy will then be evaluated for all patients entered at the RP2D. Primary objectives of the Phase 1b are to assess safety, identify RP2D, and assess preliminary efficacy of BXQ-350 in this combination. A secondary objective is to determine if BXQ-350 decreases CIPN. Design of the Phase 2, a doubleblinded, placebo-controlled study: Eligible patients (up to 160 patients) will be randomized in a 1:1 fashion to receive either BXQ-350 or placebo with mFOLFOX7 + Bevacizumab. Primary and secondary objectives include efficacy, safety and CIPN incidence. Enrollment in the Phase 1b dose escalation portion is completed. After review of the safety results, the DSMB approved enrollment of the expansion cohort, with a planned 30 patients at the Phase 2 dose. Available Phase 1b data will be presented.

TPS227 Trials in Progress Poster Session

Phase 1/2 evaluation of revumenib in patients with advanced colorectal cancer and other solid tumors. First Author: Aparna Raj Parikh, Massachusetts General Hospital Cancer Center, Boston, MA Background: Aberrant transcription in cancer can be reversed by targeting critical epigenetic regulators. For example, in acute leukemias driven by increased HOX gene expression, inhibition of the menin-KMT2A interaction by revumenib induced remission in patients with heavily pretreated disease (Issa et al 2023). In solid tumors promoted by the aberrant activation of the Wnt/b-catenin pathway, in vitro data and in vivo studies have shown that small molecule inhibition of the menin-KMT2A interaction restricts growth, with potential therapeutic benefit in colorectal cancer (CRC), castration-resistant prostate cancer, estrogen receptor-positive breast cancer, gastrointestinal stromal tumors, and Ewing sarcoma. To test the therapeutic strategy of inhibiting the menin-KMT2A interaction in solid tumor malignancies, this study (NCT05731947) will evaluate revumenib in patients with CRC and other solid tumors. Revumenib is an oral, potent, selective inhibitor of the menin-KMT2A interaction. Methods: This phase 1/2 study is evaluating revumenib in adults aged $18 years with locally recurrent or metastatic CRC who have failed $1 prior line of therapy and in patients with other solid tumors who have failed available standard therapies. Inclusion criteria include diagnosis of microsatellite stable/proficient mismatch repair CRC or other solid tumors. Patients with CRC must be unable to receive or have disease that progressed on oxaliplatin, irinotecan, and bevacizumab; if left-sided RAS wild-type CRC, the patient must have received anti-epidermal growth factor receptor therapy. The primary phase 1 objectives are to determine the safety, tolerability, maximum tolerated dose, and recommended phase 2 dose of revumenib in patients with CRC and other solid tumors and to assess its antitumor effects. The phase 2 primary objective is to assess the antitumor effects of revumenib by blinded radiographic review. Phase 1 consists of all-comers' dose escalation (phase 1a), and signal-seeking expansion in CRC (phase 1b). Using a rolling 6 design, the revumenib starting dose will be 163 mg 3 times daily in 28-day cycles. Up to 6 patients will be enrolled in a dose cohort. Dose escalation cohorts may be expanded and used for signal seeking in non-CRC tumor types. Phase 1b in CRC will begin when a potential phase 2 dose has been identified. The disease control rate at 6 cycles and overall response rate will be used to assess antitumor activity and will determine initiation of phase 2. In phase 2, patients with advanced CRC will be randomized 2:1 to revumenib or investigator's choice of 1 of 2 standard-of-care therapies. Patients will be followed for progression-free survival, with response assessments evaluated locally and confirmed by blinded radiographic review. As of September 5, 2023, 13 patients were enrolled in phase 1a of this study. Clinical trial information: NCT05731947. Research Sponsor: Syndax Pharmaceuticals.

TPS228 Trials in Progress Poster Session

An open-label clinical trial of RP2 and RP3 oncolytic immunotherapy in combination with atezolizumab plus bevacizumab for the treatment of patients with advanced colorectal carcinoma. First Author: Heinz-Josef Lenz, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA Background: Colorectal cancer (CRC) is the third most frequently diagnosed cancer and the second leading cause of cancer-related mortality worldwide. PD-1/PD-L1 inhibition, in combination with other modalities, has demonstrated significant benefit in patients (pts) with microsatellite instability-high or mismatch repair-deficient CRC. However, these agents have limited, if any, clinical benefit in pts with microsatellite stable (MSS) or mismatch repair-proficient (pMMR) CRC. RP2 is an enhanced potency oncolytic herpes simplex virus type 1 which expresses the fusogenic gibbon ape leukemia virus glycoprotein with the R sequence deleted (GALV-GP-R-), granulocyte-macrophage colony-stimulating factor (GM-CSF), and an anti-CTLA-4 antibody-like molecule; RP3 additionally expresses 4-1BB and CD40 activating ligands but does not express GM-CSF. Both agents have demonstrated preliminary safety and antitumor activity in pts with solid tumors. This study will evaluate the safety and activity of RP2 and RP3 in combination with atezolizumab (Atezo) plus bevacizumab (Bev) in pts with advanced MSS/pMMR CRC (NCT05733611). Methods: Pts with a histologic diagnosis of unresectable and/or metastatic CRC, with documented MSS or pMMR status, and previously treated with up to 3 standard-of-care systemic regimens will be enrolled in the RP2 + Atezo + Bev or RP3 + Atezo + Bev treatment groups (30 pts per group). Further key inclusion criteria include Eastern Cooperative Oncology Group performance status 0 to 1 and adequate hepatic, renal, and hematologic function. RP2/RP3 will be injected into tumors by direct or image-guided injection. Pts will receive 8 total doses of up to 10 mL of RP2 or RP3, with a first dose concentration of 1 3 10 6 plaque-forming units (PFU)/mL, followed by 3 doses of 1 3 10 7 PFU/mL every 2 weeks, and then 4 doses of 1 3 10 7 PFU/ mL every 3 weeks. Pts may receive a second course of up to 8 injections of RP2/RP3 if study criteria are met. Bev will be administered starting on week 1; Atezo will be administered starting week 7. The primary endpoint is objective response rate; secondary endpoints are safety, overall survival, progression-free survival, duration of response, and complete response rate. Antitumor activity will be evaluated using Response Evaluation Criteria in Solid Tumors version 1.1 as modified for this study. Safety will be assessed by physical examination, clinical laboratory evaluations, vital signs, and monitoring for adverse events (AEs; including serious AEs Given the proven efficacy of triplet chemotherapy in metastatic colorectal cancer, this study aims to assess the effectiveness and toxicity of modified 5-fluoropyrimidine (5-FU)/ leucovorin plus irinotecan and oxaliplatin (mFOLFIRINOX) in comparison with the current standard of care-modified oxaliplatin and 5-FU (mFOLFOX-6)-as an adjuvant treatment for patients diagnosed with high-risk stage III colon cancer. Methods: This multicenter, randomized (1:1), open-label, phase II trial aims to compare the adjuvant treatment efficacy of mFOLFIRINOX and mFOLFOX-6 in patients with high-risk stage III colon cancer. The trial aimed to enroll 312 eligible patients aged between 20 and 70 years with an Eastern Cooperative Oncology Group performance status of 0-2, or between 70 and 75 years with an Eastern Cooperative Oncology Group performance status of 0. All patients underwent radical resection and were randomized into two arms: Arm A experimental arm, received 12 cycles of mFOLFIRINOX every 2 weeks, while arm B, the reference arm, received 12 cycles of mFOLFOX 6 every 2 weeks. The primary endpoint of this study was the 3-year disease-free survival, whereas the secondary endpoints included assessing the 3-year overall survival and treatment toxicity. Discussion: The Frost trial is expected to elucidate the safety and oncologic efficacy of mFOLFIRINOX compared to mFOLFOX 6 as adjuvant treatment for high-risk stage III colon cancers, and provide evidence about this treatment, and contribute to improve the prognoses ultimately. Clinical trial information: NCT05179889. Research Sponsor: The Korean Society of Coloproctology; Korea National Enterprise for Clinical Trial.

TPS231 Trials in Progress Poster Session

Colorectal cancer metastatic dMMR immuno-therapy (COMMIT) study: A randomized phase III study of atezolizumab (atezo) monotherapy versus mFOLFOX6/bevacizumab/atezo in the first-line treatment of patients (pts) with deficient DNA mismatch repair (dMMR) or microsatellite instabilityhigh (MSI-H) metastatic colorectal cancer (mCRC)-NRG-GI004/SWOG-S1610. First Author: Michael J. Overman, The University of Texas MD Anderson Cancer Center, Houston, TX

Background: Approximately 45% of dMMR/MSI-H mCRC in the immunotherapy arm progressed at 12 mos (KEYNOTE 177). We hypothesize that dMMR/MSI-H mCRC pts may be more effectively treated with the combination of PD-1/PD-L1 (PD-1) pathway blockade and mFOLFOX6/bevacizumab (bev) rather than with anti-PD-L1 therapy (atezo) alone. Preclinical work demonstrated synergistic effects between anti-PD-1/anti-VEGF as well as between oxaliplatin/anti-PD-1 in murine CRC models, and phase II data showed activity of anti-PD-1/ anti-VEGF in chemotherapy refractory colon cancer. QD or BID (25 to 800 mg total daily; arm 1) and pts with previously untreated non-smallcell lung cancer (NSCLC) with PD-L1 tumor proportion score $1% receiving MK-1084 from 25 to 400 mg total daily dose plus pembrolizumab 200 mg IV Q3W (arm 2). Toxicity was manageable during dose escalation of these 2 arms. Based on these initial findings, the study design has been updated to assess an alternate MK-1084 formulation and MK-1084 in combination with other therapies in KRAS G12C-mutated tumors. We present the study design for the new arms that include patients with gastrointestinal cancers. Methods: Eligible pts are aged $18 years with measurable disease per RECIST version 1.1 by investigator, ECOG performance status 0/1, adequate organ function, and advanced solid tumors (arm 3), or metastatic CRC with progression on 1 or 2 lines of prior therapy (arm 5), or previously untreated metastatic CRC (arm 6), all with KRAS G12C mutation. Pts in arm 3 receive the alternate MK-1084 formulation. Pts in arms 5 and 6 receive MK-1084 with one of the following: cetuximab 500 mg/m 2 IV Q2W (arm 5); or cetuximab 500 mg/m 2 IV Q2W, oxaliplatin 85 mg/m 2 , leucovorin 400 mg/m 2 , and 5-fluorouracil per label IV Q2W (arm 6). Each arm has a safety run-in prior to expansion. The primary objective is to assess the safety and tolerability of MK-1084 as monotherapy and in combination with these other agents. Secondary endpoints include objective response and duration of response. AEs will be evaluated from baseline through 30 days after cessation of study treatment (90 days for serious AEs). Tumor imaging by CT or MRI will be performed at baseline, every 6 weeks up to week 18, every 9 weeks for the remainder of the first year, and then every 12 weeks. Radioimmunotherapy offers a promising therapeutic modality for rectal cancer. Progenitor T exhausted cells are abundant in tumour-draining lymph nodes and play an important role in immunotherapy. Conventional irradiation fields include the mesorectum and regional lymph nodes, which might cause considerable damage to T lymphocytes and radiation-induced fibrosis, ultimately leading to a poor response to immunotherapy and rectal fibrosis. This study investigated whether node-sparing modified short-course irradiation combined with chemotherapy and PD-1 blockade could be effective in patients with microsatellite stable locally advanced rectal cancer. Methods: Our clinical trial investigates the safety and efficacy of node-sparing modified short-course radiotherapy combined with CAPOX and tislelizumab for microsatellite stable locally advanced middle and low rectal cancer. This phase II study will recruit 32 patients to receive node-sparing modified short-course radiotherapy (the irradiated planned target volume only included the primary tumour bed but not the tumour-draining lymph nodes, 25 Gy/5f, 5 Gy/f) followed by CAPOX and tislelizumab. 2 of planned 32 patients have been enrolled. CAPOX and tislelizumab will be started two days after the completion of radiotherapy: oxaliplatin 130 mg/m 2 intravenous infusion, day 1; capecitabine 1000 mg/m 2 oral administration, days 1-14; and tislelizumab 200 mg, intravenous infusion, day 1. There will be three 21-day cycles. TME will be performed at weeks 11-12. We will collect blood, tumour, and lymphoid specimens; perform flow cytometry and in situ multiplexed immunofluorescence detection; and analyse the changes in various lymphocyte subsets. The primary endpoint is the rate of pathological complete response. The organ preservation rate, tumour regression grade, local recurrence rate, disease-free survival, overall survival, adverse effects, and quality of life will also be analysed.

TPS235 Trials in Progress Poster Session

Phase 2A trial of Ad5.F35-GUCY2C-PADRE vaccine for recurrence prevention in gastrointestinal (GI) adenocarcinomas post definitive surgery and adjuvant therapies. First Author: Babar Bashir, Sidney Kimmel Cancer Center at Thomas Jefferson University Hospital, Philadelphia, PA Background: A significant proportion of patients with GI adenocarcinomas remain at high risk of recurrence despite adjuvant therapies. Guanylyl cyclase C (GUCY2C) is expressed by normal intestinal cells and immunologically compartmentalized. Its overexpression in GI adenocarcinomas makes it an appealing target for anti-cancer therapies. We previously completed a phase I study of the Ad5-GUCY2C-PADRE vaccine in patients (pts) where it was safe and well tolerated (NCT01972737). Pre-existing neutralizing antibodies (NAbs) to the Ad5 vector opposed vaccine-induced immune responses. To overcome this challenge, we generated a GUCY2C vaccine employing a chimeric viral vector composed of the Ad5 capsid and Ad35 fiber protein (Ad5.F35). The extracellular domain of GUCY2C, along with the PADRE CD4 + helper T-cell epitope, were cloned into the Ad5.F35 viral vector to generate a replication-incompetent vaccine. Preclinical studies showed that Ad5.F35-GUCY2C-PADRE was less sensitive to pre-existing Ad5-specific immunity. Methods: This is a Phase 2A, dose-finding, single-center, open-label, randomized trial (NCT04111172) to evaluate the safety and immunogenic activity of three dose levels of Ad5.F35-GUCY2C-PADRE vaccine in adult pts with select solid tumors (colorectal, pancreatic, gastric, esophageal, or small bowel) who are at risk of relapse post definitive surgery and adjuvant therapy. Pts must enroll at 4-24 weeks from completion of standard therapies. Other key eligibility requirements include ECOG status of 0-1 and adequate organ function. Pts are randomized to one of three dose levels (10 11 vp or viral particles, 10 12 vp, or 5x10 12 vp) with stratification by disease type. After completing an initial safety run-in for 9 pts (3 pts in each arm), the study will recruit up to 81 pts in total (27 in each arm). Pts will receive three successive doses of vaccine (4 weeks apart) and will undergo end-of-treatment assessment 4 weeks after their last vaccine. Pts are followed for disease status by scheduled follow-up until 2 years or recurrence, whichever occurs first. An interim futility analysis will be performed after 15 patients have completed treatment in each arm based on the Simon minimax design. Study objectives include assessment of safety and tolerability (primary), as well as T-cell and antibody responses to GUCY2C (secondary). Additional exploratory objectives include evaluating the relationship between NAbs and immune responses to GUCY2C, GUCY2C protein expression in tumors, circulating tumor DNA kinetics in relation to vaccination, and disease-free and overall survival (where applicable).

TPS236 Trials in Progress Poster Session

Alliance A022101: A pragmatic randomized phase III trial evaluating total ablative therapy for patients with limited metastatic colorectal cancer-Evaluating radiation, ablation, and surgery (ERASur). First Author: Kathryn Hitchcock, University of Florida/UF Health Cancer Center, Gainesville, FL Background: For patients with oligometastatic colorectal cancer (CRC), aggressive local therapy of isolated metastases, particularly in the liver, has been associated with long-term progression-free survival and overall survival (OS) primarily based on retrospective evidence. However, in patients with limited metastatic CRC that is deemed inoperable or those with additional disease outside of the liver or lungs, the role of local ablative therapies, including microwave ablation (MWA) and stereotactic body radiation therapy (SBRT), to render patients disease free is less clear. Further, despite the long history of treating oligometastatic CRC with local therapy, which is provider biased and not evidence based, questions remain regarding the benefit of extending the paradigm of metastatic directed therapy to patients with more extensive disease. This trial seeks to use a pragmatic multimodality approach that mirrors the current clinical dilemma. This study is designed to evaluate the safety and efficacy of adding total ablative therapy (TAT) of all sites of disease to standard of care systemic treatment in those with limited metastatic CRC. Methods: A022101 is a National Clinical Trials Network randomized phase III study planned to enroll 364 patients with newly diagnosed metastatic CRC (BRAF wild-type, microsatellite stable) with #4 sites of metastatic disease on baseline imaging. Liver-only metastatic disease is not permitted, and lesions must be amenable to any combination of surgical resection, MWA, and/or SBRT with SBRT required for at least one lesion. Patients receive first-line systemic therapy for 4-6 months and are then randomized 1:1, stratified by number of metastatic organ sites (1-2 vs. 3-4), timing of metastatic disease diagnosis (de novo vs. secondary), and presence of metastatic disease outside the liver and lungs in at least one site. Patients in Arm 1 will receive TAT which consists of treatment of all metastatic sites with SBRT 6 MWA 6 surgical resection followed by standard of care systemic therapy. Patients in Arm 2 will continue with standard of care systemic therapy alone. The primary endpoint is OS. Secondary endpoints include event-free survival, treatment-related toxicities, and local recurrence with exploratory biomarker analyses. The study needs 346 evaluable patients combined in the 2 arms to demonstrate an improvement in OS with a hazard ratio of 0.7 to provide 80% power with a one-sided alpha of 5%. The trial utilizes a group sequential design with two interim analyses (25% and 50% of events) for futility. The trial activated in January 2023 and recruitment is ongoing. Support: U10CA180821, U10CA180882; https://acknowledgments.alliancefound.org. U10CA180820 (ECOG-ACRIN); U10CA180868 (NRG); U10CA180888 (SWOG). Clinical trial information: NCT05673148.

Research Sponsor: NCI-NCTN.

No operation after short course radiotherapy followed by consolidation chemotherapy in locally advanced rectal cancer: The prospective, single arm NOAHS-ARC trial. First Author: Felipe Fernando Quezada, Complejo Asistencial Doctor Sotero del Rio, Santiago, Chile Background: A Watch and Wait (W & W) strategy has been advocated for selected patients with a locally advanced rectal cancer (LARC) and a clinical complete response (cCR) after neoadjuvant treatment (NAT). In this context, total neoadjuvant therapy (TNT) has emerged as a strategy to enhance treatment response. Currently, TNT has reported higher rates of pathological complete response (pCR) and organ preservation when compared to long course radiotherapy (LCRT). However, the best TNT strategy is still unknown. We therefore hypothesize that in LARC patients, the use of a TNT strategy based on short course radiotherapy (SCRT) followed by consolidation chemotherapy is associated with a higher rate of pCR and sustained (.1year) cCR when compared to an historic cohort treated with LCRT. Methods: This is a prospective, single arm, phase II study that is currently enrolling patients with LARC (AJCC TNM cT3-T4 w/wo secondary lymph nodes according to clinical staging) . 18 years old from a tertiary hospital from Santiago, Chile. We included patients with biopsy proven palpable (,7cm from anal verge) adenocarcinoma from the middle-lower rectum.

We excluded patients with contraindications to SCRT and/or chemotherapy. All patients receive SCRT (5x5 Gy) followed by systemic consolidation chemotherapy 7-14 days after last dose of SCRT, using either 9 cycles of FOLFOX or 6 cycles of CAPOX. Patients will be evaluated to determine the degree of response at 3 time points during TNT: baseline, mid-TNT (9 weeks after TNT beginning) and post-TNT (18 weeks after TNT beginning). At each time point, patients will be clinically evaluated with a DRE, flexible sigmoidoscopy (photos & video) and a magnetic resonance image of the rectum. CT scan will be performed at baseline and complete TNT. Treatment response will be categorized as cCR, near-cCR and incomplete response (IR) according to the Memorial Sloan Kettering Regression Schema previously validated in the OPRA Trial. Patients with an IR will be offered TME. Patients with a cCR will be offered a W & W strategy, if accepted. Patients with a near-cCR will be evaluated again in 4 weeks to define cCR versus IR. In cases of TME, surgical specimens will be processed in a standardized manner and tumor regression grade will be assessed using the American College of Pathologist's Scale. Additionally, validated quality of life questionnaires will be administered at the baseline, post-NAT and at 6,12 and 24 months of follow-up. Finally, a repository for endoscopic/MRI imaging, tumoral tissue and serum will be obtained. For statistical analysis, an a level of error of 5% will be set. For sample size calculation, a pCR rate of 12% was used based in historic data. Using a previously reported design and considering a 30% of combined pCR/sustained cCR, sample size to prove statistical significance with b power of 80% and error of 10% will be 73 patients. Clinical trial information: NCT04864067. Research Sponsor: Agencia Nacional de Investigaci ón y Desarrollo.

TPS238 Trials in Progress Poster Session

Combining low-dose regorafenib with pembrolizumab for patients with MSI-H colorectal cancer: REGPEM-CRC-01. First Author: Ibrahim Halil Sahin, University of Pittsburgh Medical Center, Pittsburgh, PA Background: Treatment for microsatellite instability-high (MSI-H)/mismatch repair deficient (MMR-D) colorectal cancer (CRC) has rapidly evolved in the last decade. The KEYNOTE 177 trial recently established pembrolizumab as a frontline therapy for patients with MSI-H CRC. However, in this study, approximately 40% of patients were noted to have disease progression within 6 months of treatment. Furthermore, an additional 10% of patients experienced acquired resistance to therapy. Therefore, there is an unmet need to improve outcomes for patients with MSI-H CRC. Preclinical studies have shown vascular endothelial growth factor (VEGF) signaling to be overactive in MSI-H compared to MSS CRC (Hansen et al. Colorectal Dis. 2011) . Moreover, exploratory analysis of CALBG-80405 and PARADIGM trials showed that patients with MSI-H CRC were more likely to benefit from anti-VEGF therapy than those with MSS disease. Regorafenib, an FDA-approved agent for patients with mCRC, is a potent VEGF inhibitor with immune modulatory effects on the tumor microenvironment. We hypothesize that adding low-dose regorafenib to pembrolizumab as frontline therapy may create synergistic activity in addition to the known clinical activity of each agent in MSI-H CRC. Methods: In the lead-in arm of this prospective study, 22 patients will be enrolled. Patients will receive regorafenib 60 mg daily on days 1-14 (2 weeks on) followed by 7 days off (1 week off) in combination with pembrolizumab 200 mg in the cycle 1. In the following cycles, patients will receive regorafenib 90 mg daily for 2 weeks on 1 week off in combination with pembrolizumab 200 mg every 3 weeks. The primary outcome for the lead-in arm is overall response rate (ORR) within 12 months of treatment by RECIST 1.1. criteria. A formal one-sided hypothesis test will be conducted for futility, assuming that we will reject the null hypothesis of a target ORR only if we have strong evidence. In this study, we assume a null hypothesis that ORR is 0.60, which would reflect significant clinical improvement over the current standard of ORR = 0.43 from KEYNOTE 177. The alternative hypothesis is that ORR is less than 0.60. For the lead-in phase of the study, the emphasis is on controlling Type I error to be small, approximately 0.05. In the randomized phase of the study, patients will receive pembrolizumab monotherapy or pembrolizumab in combination with regorafenib 90 mg.

The sample size for the randomized phase of trial was determined based on an assumed median of PFS of 28 months with pembrolizumab and regorafenib combination (investigational arm). The standard of care pembrolizumab monotherapy results in a median PFS of 16 months when given as a first-line therapy. We hypothesize the proposed treatment will increase median PFS to 28 months from 16 months (N=132; H0: 16 months vs., H1: 28 months; Type I error: 0.05, power 80%). Clinical trial information: NCT06006923. Research Sponsor: None.

TPS239 Trials in Progress Poster Session

A phase 1/2 study of REGN7075 (EGFRxCD28 costimulatory bispecific antibody) in combination with cemiplimab (anti-PD-1) in patients with advanced solid tumors, including colorectal cancer: Trial in progress update. First Author: Neil Howard Segal, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY Background: REGN7075 is a human costimulatory bispecific antibody designed to bridge epidermal growth factor receptor (EGFR)-expressing tumor cells with CD28 on the surface of T cells to drive co-stimulation and recognition of endogenous tumor antigens. EGFRtargeted therapies are approved in head and neck squamous cell carcinoma, non-small cell lung cancer (NSCLC), and colorectal cancer (CRC). Methods: This is an open-label, Phase 1/2, first-in-human, international study evaluating the safety, tolerability, PK, and antitumor activity of REGN7075 6 cemiplimab (anti-PD-1) in patients (pts) with solid tumors (NCT04626635). Here we focus on the cohorts of pts with microsatellite-stable-CRC (MSS-CRC). The study includes a dose-escalation phase (Part 1) and a dose-expansion phase (Part 2). In Part 1, pts will receive a 3-week REGN7075 monotherapy once-weekly (QW) lead-in prior to combination therapy with REGN7075 QW or every 3 weeks (Q3W) + cemiplimab Q3W. Concurrent Q3W dosing with cemiplimab may be conducted for dose levels for which the lead-in is tolerable; to date, this has been up to a dose of 900 mg. After a tolerable dose and schedule of interest is identified in Part 1, Part 2 may consist of eight tumor-specific expansion cohorts, including two cohorts of pts with metastatic MSS-CRC or locally advanced CRC (not candidates for curative surgery/radiation), who have received at least one prior line of therapy (anti-EGFR for RAS wild type disease, anti-VEGF, or documented reason why not appropriate). One cohort will include pts with MSS-CRC with active liver and/or peritoneal metastases, and the other will include pts with MSS-CRC with only lung and/or lymph node metastases. Overall, key inclusion criteria are: evidence of a protocol-defined advanced solid tumor, an ECOG performance status of 0 or 1, and no previous anti-PD-1/anti-PD-(L)1 therapy (Part 2 only). The analyses of Part 1 will be descriptive and exploratory in nature. . Pts stratified by clinical tumor/node (TN) staging will be randomized 2:1 to receive dostarlimab pre-and post-surgery, or surgery followed by SOC (adjuvant FOLFOX/CAPEOX for 3-6 months or watch and wait approach per physician's discretion). Primary endpoint is event-free survival (EFS) (events: recurrence based on radiological assessment by blinded independent central review or pathological assessment of new lesions, disease progression precluding surgery, treatment (tx)-related toxicity precluding surgery, or death).

278 Poster Session

Ten-year overall survival of localized lower thoracic and esophagogastric junction carcinoma receiving trimodality therapy: A National Cancer Database analysis. First Author: Hanna Kakish, University Hospitals Cleveland Medical Center, Cleveland, OH Background: Trimodality therapy, consisting of chemotherapy and radiation followed by esophagectomy, represents the prevailing standard of care for most patients with localized lower thoracic and esophagogastric junction (EGJ) carcinoma. However, robust data reporting the survival of this patient group treated in the real-world setting is lacking. The primary objective of the current study was to comprehensively analyze the long-term survival of this patient population receiving treatment in a real-world setting and the variables that significantly influence the survival. Methods: We identified adult patients in the National Cancer Database with localized (cT1N+M0 or cT2-T4N+/-M0) lower thoracic or EGJ adenocarcinoma (AC) or squamous cell carcinoma (SCC) receiving trimodality therapy between 2004 and 2020 with multi-agent chemotherapy and $ 4139 cGy of radiation followed by esophagectomy. The primary endpoint of the analysis was overall survival (OS), estimated using the Kaplan-Meier method. The impact of clinical and demographic features on OS was determined using the log-rank test. We performed a multivariable (MV) Cox analysis to evaluate the independent association of clinical and demographic variables on OS (data presented as hazard ratio [HR] and 95%

279 Poster Session

Comprehensive molecular characteristics of clinical responses to PD-1 inhibitors plus anti-angiogenic agents (PA) in metastatic HER2-negative gastric adenocarcinoma. First Author: Jingyuan Wang, Department of Medical Oncology, Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China Background: Anti-angiogensis agents were reported to enhance the efficacy of PD-1 inhibitor by inhibiting the infiltration of suppressive immune cell populations. Clinical studies indicated the synergistic anti-tumor effect of the combination of PD-1 inhibitors and anti-angiogenesis agents (PA). We aim to assess the efficacy of PA versus chemo-PA regiment in mGC, as well as the potential predictive biomarkers. Methods: A total of 55 GC tumors were analyzed using the next-generation sequencing (NGS

283 Poster Session

Quality of life (QOL) for patients with esophageal cancer receiving trimodality therapy with induction chemotherapy, chemoradiation, and surgery: Results from CALGB 80803 (Alliance). First Author: Karyn A. Goodman, Icahn School of Medicine at Mount Sinai, New York, NY Background: The randomized phase II CALGB 80803 trial evaluated use of PET imaging for early assessment of induction chemotherapy (iCT) responsiveness to tailor therapy for patients with esophageal and gastroesophageal junction adenocarcinomas (EC) undergoing trimodality therapy. The primary endpoint of improving pathologic complete response rates using PET-adapted therapy was met. A companion QOL study aimed to characterize patients' experience through iCT, chemoradiation (CRT) and surgery (S). Methods: Between 11/2011 and 5/2015, 241 eligible patients were randomized to an iCT regimen: modified oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) or carboplatin/paclitaxel (CP), followed by PET scan then CRT, either continuing on the same CT for PET-responders (PET-R) or crossing over to the alternative CT for PETnonresponders (PET-NR). We prospectively collected QOL domains and symptoms at baseline (T1), after iCT (T2), after CRT (T3), and 3-(T4) and 6-months (T5) after S using the EORTC QLQ-C30, The Esophageal Cancer subscale (EORTC OES18), FACT Neurotoxicity Scale (FACT-NTX), and 6 questions from the PRO-CTCAE. QOL scores were compared between iCT groups and between PET-R and PET-NR at each time point using mixed models. The association of QOL scores at enrollment with overall survival (OS) was tested using Cox regression. Results: 189 patients enrolled on the QOL sub-study, 92 received induction FOLFOX and 97 induction CP. Of those, 110 were PET-R and 79 were PET-NR. 97.9% went on to CRT, and 83.6% underwent S. Global QOL and symptoms statistically significantly worsened from T1 to T2 in 14 of 25 domains, and remained significantly worsened from T1 at: T3 for 19 of 25 domains, T4 for 17 of 25 domains, and T5 for 6 of 25 domains. Changes from T1 significantly favored iFOLFOX (vs iCP) for ability to eat (at T3 and T4), GI symptoms (at T3 and T4), and talking (at T5). Changes from T1 significantly favored iCP (vs iFOLFOX) for neuropathy (at T2, T3, and T4) and coughing (at T5

287 Poster Session

Tumor regression grade after neoadjuvant chemotherapy in patients with locally advanced gastric cancer treated with modern chemotherapy (FLOT): Experience in patients in Guatemala. First Author: Rixci Ramirez, Instituto Guatemalteco de Seguridad Social, Guatemala, Guatemala

Background: Perioperative chemotherapy is the standard of care for locally advanced gastric cancers in Western populations. At this moment perioperative chemotherapy with FLOT (Fluorouracil, leucovorin, oxaliplatin and docetaxel) regimen is recommended in patients who are medically fit with benefit in progression-free survival (PFS) and overall survival (OS). However, the impact of response to this treatment is not well established. The objective of this study is to find the pathological response to FLOT chemotherapy measured by the degree of tumor regression (TRG), the benefit on disease-free survival (DFS) and OS, in patients with gastric cancer locally advanced treated with FLOT chemotherapy. Methods: Patients from the Instituto Guatemalteco de Seguridad Social (IGSS) from Guatemala City, who underwent radical gastrectomy for non-metastatic invasive gastric adenocarcinoma after perioperative chemotherapy (T1-4/N0/N+cM0) from 2019 to 2023 were included. Demographic data, clinical staging, histologic phenotype, surgical factors, tumor regression grade after gastrectomy and survival outcomes were included. The association between ORR and OS were evaluated. OS and DFS were estimated using the Kaplan Meier method with adjustment for covariates using Cox regression. Results: Thirty-eight patients with locally advanced cancer gastric were identified.

The median age was 58 years (29-79), most of the patients were men (23, 61%), 35 (92%) patients have primary gastric tumor, 26 (68%) has cT3/T4 tumors and 22 (58%) has intestinal gastric cancer, all patients underwent to surgery. Two patients (6%) had TRG of 1 (complete and almost complete), 8 patients (21%) had an TGR of 2, and 28 patients (74%) had an TGR of 3; 13 patients (38%) developed recurrence, median DFS was 5.2 months (95% CI: 1.0-28). The median OS was 15.3 months (95% CI: 3.0-45). Lack of tumor regression (TRG 3) was significantly associated with lower survival HR 1.42 (1.05-2.24) p= 0.008. Clinical T4 tumors and diffuse histology were associated with poor prognostic (cT4 HR 3.04, p = 0.038, diffuse histology HR 2.08 (p = 0.001) (Table ). Conclusions: Since cT4 tumors are an independent risk factor associated with poor prognostic HR 3.04, p = 0.038, it is important to make an adequate clinical staging before deciding to use three-drug treatment regimens of chemotherapy. Other factors in addition to clinical ones should be investigated, such as molecular factors that may be related to this poor response and survival in patients with cT4. This study of molecular factors is currently underway at our institution. Research Sponsor: None.

294 Poster Session

Association of intensifying supportive care with improved survival in patients with gastric cancer with malignant ascites. First Author: John D Karalis, University of Texas Southwestern Medical Center, Dallas, TX Background: Gastric cancer patients with malignant ascites often have poor functional status and malnutrition that precludes receipt of systemic therapies. Thus, these patients have a very poor prognosis. Beginning in 2019, our multidisciplinary gastric cancer disease-oriented team implemented a more aggressive supportive care plan for gastric cancer patients with malignant ascites. The initiative included measures such as supplemental enteral nutrition, ascites drainage, and initiation of chemotherapy on an inpatient basis. We compared outcomes for gastric cancer patients who presented with synchronous malignant ascites treated before and after the implementation of the care plan. Methods: We performed a retrospective review of our institutional database to identify patients diagnosed with gastric adenocarcinoma and synchronous malignant ascites between 2010-2022. We compared survival between patients diagnosed from 2010-2018, which will be referred to as the historical control era and patients diagnosed from 2019-2022, which will be called the aggressive supportive care era. Results: 54 patients were included in our analysis; 31 patients were treated in the historical control time frame and 23 patients treated during the aggressive supportive care era. Demographic, clinical, and pathologic characteristics were similar between groups. 3% of historical controls received supplemental tube feeds at diagnosis as compared to 30% of the aggressive supportive care cohort (p=0.008). 3% of historical controls received their first cycle of chemotherapy in the inpatient setting versus 39% of patients treated during the aggressive supportive care era (p=0.001). The median number of chemotherapy cycles received was 5 among historical controls and 9.5 among aggressive supportive care era patients (p = 0.02). There was no difference in the number of days spent as an inpatient between the two groups. The median overall survival for historical control patients was 5.4 months as compared to 10.4 months for patients treated during aggressive supportive care era (p=0.035). Conclusions: Gastric cancer patients with synchronous malignant ascites treated during a timeframe when our multidisciplinary team implemented more aggressive supportive care measures had improved OS as compared to historic controls.Our results suggest that aggressive supportive measures for these patients with highly challenging clinical issues and poor prognosis can prolong survival. Specifically, initiation of chemotherapy in the inpatient setting and supplemental nutrition should be considered for patients at high risk for treatment intolerance.

Research Sponsor: Burroughs Wellcome Fund; 1018897.

295 Poster Session

Real

296 Poster Session

A multi-institutional prospective study to compare postoperative quality of life of patients who undergo proximal or total gastrectomy for early gastric cancer (CCOG1602). First Author: Yumiko Hojo, Department of Surgery, Komaki Municipal Hospital, Komaki, Japan Background: Proximal gastrectomy (PG) has become an increasingly preferred procedure for treating early cancer in the upper third of the stomach when oncological safety is ensured, with expectation for improvement of nutritional status and quality of life (QOL) attributable to the remnant stomach. Although few studies compare postoperative outcomes of patients who undergo total gastrectomy (TG) and PG based on questionnaires, their significant limitations include the retrospective design, use of a questionnaire not specific to a postgastrectomy setting, and observation at a fixed time or after a short postoperative period. Methods: A multi-institutional prospective study (CCOG1602) of patients who undergo PG or TG for cStage I gastric cancer was conducted. We used the Post-Gastrectomy Syndrome Assessment Scale (PGSAS)-37 and The European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC-QLQ-C30) to evaluate the changes in body weight and QOL over a 3-year postoperative period. The primary endpoint was the weight loss rate 3 years after surgery. Results: We enrolled 109 patients from 18 institutions and selected 65 and 19 patients for inclusion in the TG and PG groups, respectively. There were no differences in age, sex, or preoperative body mass index between the TG and PG groups. Mean postoperative weight loss rates were 16.0% and 11.7% for the TG and PG groups, respectively (Cohen's D 0.656) during postoperative year 1 and 15.0% and 10.8% for TG and PG (Cohen's D 0.543), respectively, during postoperative year 3, indicating that the PG group achieved a better trend with a moderate effect size. According to the PGSAS-37, the PG group experienced a better trend in the indigestion subscale (Cohen's D -1.085) and total symptom score (Cohen's D -0.59) during postoperative year 3 compared with the TG group. In contrast, the EORTC-QLQ-C30 identified no difference between the groups at any time point during the 3-year postoperative period.

Conclusions: The CCOG1602 demonstrates that PG tended to be more favorable compared with TG with respect to postoperative weight loss and QOL, particularly regarding indigestion.

302 Poster Session

Prospective study to assess taste related to eating disorders during chemotherapy using a dietary app: OISHY study. First Author: Toshiharu Hirose, National Cancer Center Hospital, Chuo City, Japan Background: Adverse events (AE) such as nausea, vomiting, dysgeusia, oral mucositis, and anorexia during chemotherapy can lead to eating disorders. Nutritional specialists provide supportive care by intervening based on these symptoms. However, individual patients have diverse taste complaints, making assessment difficult. Recently, dietary apps have been developed that offer dietary recommendations and enable patients to record meals based on the patient's condition. In this study, we utilized a dietary app to record meals and quantify taste. The aim was to objectively assess the details of taste for AEs related to eating disorders. Methods: Patients diagnosed with gastrointestinal cancer between March 2021 and June 2022 at our hospital who received chemotherapy were included in the study. Patients searched for food recommendations using the dietary app according to their symptoms and recorded their meals. For each meal, the amount of intake and taste were recorded. Taste was recorded on a scale of 1-100 for sweet, salty, sour, bitter, umami, and spicy, with 1 indicating the weakest flavor and 100 the strongest. AEs that could cause eating disorders were assessed using CTCAE ver. 5.0 and taste was examined for each AE. Results: A total of 18 patients (9 with esophageal cancer, 8 with colorectal cancer, and 1 with gastric cancer) were enrolled in this study.

Palliative chemotherapy was given to 9 patients and preoperative chemotherapy to 9. AEs (any grade) related to chemotherapy-induced eating disorders were anorexia in 13 patients, dysgeusia in 12, nausea in 10, and oral mucositis in 7. Compared with all patients, in anorexia there were no obvious sensitivities for any tastes, but the intake amount was decreased. In dysgeusia, patients less strongly perceived sweet and spicy, but more strongly perceived salty and umami. In nausea, the patients ate less and less strongly perceived bitter, umami, and spicy. In oral mucositis, sweet and sour tastes were perceived less strongly. Conclusions: By using a dietary app, detailed taste could be quantified for chemotherapy AEs related to eating disorders. Further large-scale studies may be needed. Clinical trial information: UMIN000046647.

303 Poster Session

Efficacy and safety of nivolumab and CapeOX in patients with previously untreated FGFR2-positive, PD-L1-positive advanced gastric cancer: A singlearm, multicenter, phase 2 study NIVOFGFR2. First Author: Ilya Tsimafeyeu, Bureau for Cancer Research -BUCARE, New York, NY Background: Nivolumab in combination with chemotherapy has been approved in the first-line treatment of PD-L1-positive metastatic gastric cancer (GC). Fibroblast growth factor receptor 2 (FGFR2) is overexpressed in 30% of patients with GC and is a potential new target for targeted therapy with monoclonal antibodies 1 or allosteric extracellular inhibitors. 2 The aim of the NIVOFGFR2 study was to evaluate the preliminary efficacy of nivolumab in metastatic GC co-expressing PD-L1 and FGFR2. Methods: In this single-arm, multi-center, phase 2 study, eligible patients had metastatic untreated HER2-negative gastric adenocarcinoma with centrally confirmed expression of PD-L1 (CPS$5; DAKO 28-8) and FGFR2 (moderate (2+) and strong (3+) membranous staining in more than 1% of tumor cells; Absam EPR24075-418). Patients received nivolumab 360 mg with CapeOX (capecitabine and oxaliplatin) every 3 weeks. The primary endpoint was 1-year progression-free survival (PFS). Secondary endpoints included median PFS and overall survival (OS), objective response rate (ORR) and Grade $3 adverse events rate. Results: Seventy-four HER2-negative patients were screened and23 (31%) patients were enrolled (median age 61 years, men 74%, Caucasian 91%, ECOG PS 1-2 78%, organs with $2 metastases 78%; CPS (5-9) 22%, ($10) 78%

311 Poster Session

Larynx-preserving treatment strategy for patients with resectable cervical esophageal squamous cell carcinoma. First Author: Yasuhiro Tsubosa, Division of Esophageal Surgery, Shizuoka Cancer Center, Shizuoka, Japan Background: Preservation of the larynx is an important treatment strategy for cervical esophageal squamous cell carcinoma (CESCC), because surgery for CESCC often involves laryngectomy. At our hospital, we actively perform dCRT (cisplatin + 5fluorouarcil + radiation 60Gy) to preserve laryngeal function. In this study, we compared the treatment results of esophagectomy and definitive chemoradiation (dCRT) for resectable CESCC and examined larynx-preserving treatment strategies. Methods: Patients who were treated for resectable CESCC at our hospital from January 2003 to March 2019 were divided into surgery group and dCRT group for the initial treatment. All patients were eligible for both treatments. The treatment results were compared retrospectively. Results: Of all 61 patients, 23 patients received surgery and 38 received dCRT. There was no significant difference in patients' characteristics between 2 groups. In surgery group, 19 cases lost their laryngeal function by surgery (82.6%). Recurrence was observed in 7 cases, of which only 3 case was local. In CRT group, 33 cases (86.8%) achieved complete response, of which 16 cases relapsed. 8 cases (21.1%) lost their laryngeal function by additional surgery after dCRT. There was no significant difference in 5-year survival rate between two groups (surgery, 60.8%; dCRT, 70.1%; p = 0.750). In dCRT group, 5-year laryngeal-preserving survival rate was 64.8%, and esophageal stenosis before treatment was the independent risk factor for non-larynx preservation. 5-year laryngeal-preserving survival rate was 78.5%, and 5-year survival rate was 85.4% for non-stenotic cases in dCRT group, which were significantly higher than those for stenotic cases. 5-year laryngeal-preserving survival rate was also high in the patients with Ce localized tumor (72.6%). In those patients, non-stenotic patients and cT1-T3 patients had significantly high 5-year laryngeal-preserving survival rate (87.5% and 92.3%). Conclusions: dCRT for CESCC was comparable to surgery in terms of long-term prognosis, and the rate of larynx preservation was high. Among the cases where the tumor was localized to Ce, the laryngeal preservation rate was particularly high in non-stenotic cases and cases with cT1-T3, and dCRT should be actively indicated for these cases. Research Sponsor: None.

312 Poster Session

Atezolizumab In phase 3 studies, zolbetuximab (800 mg/m 2 loading dose/600 mg/m 2 Q3W) had a manageable safety profile and was associated with significant prolongation of progression-free survival (PFS) and overall survival (OS). E-R analyses suggested that higher zolbetuximab exposure may further prolong PFS and OS but with increased probability of gastrointestinal events and infusion-related reactions. E-R model simulations suggested comparable zolbetuximab efficacy and safety between the 800/600 mg/m 2 Q3W regimen and an alternative 800/400 mg/m 2 Q2W regimen for use in combination with chemotherapy. ADAs were detected in 4.4% of patients in phase 3 studies with no apparent impact on zolbetuximab PK, efficacy, or safety. Conclusions: The clinical pharmacology of zolbetuximab was well characterized using data from 9 clinical trials. The integrated data support the proposed 800/600 mg/m 2 Q3W regimen as well as an 800/400 mg/m 2 Q2W regimen in combination with chemotherapy. Clinical trial information: NCT00909025, NCT01671774, NCT03528629, NCT04086758, NCT01197885, NCT01630083, NCT03505320, NCT03504397, NCT03653507. Research Sponsor: This study was funded by Astellas Pharma, Inc.

Model-estimated exposure metrics of zolbetuximab.

Mean (SD)

First Dose (800 mg/m 2 ) Methods: The study enrolled G/GEJ adenocarcinoma patients(pts) with CLDN18.2 positive expression. The dose-escalation phase used a 3 + 3 design to determine the maximum tolerated dose (MTD). In expansion, the dose of ASKB589 selected for expansion was based on the safety, tolerability, pharmacokinetics and antitumor activity during escalation phase. Responses were assessed by RECIST 1.1 every 2 cycles (6 weeks). Adverse events (AEs) were graded using CTCAE v5.0. In escalation, pts received ASKB589 intravenously (IV) at doses of 6 mg/kg (n = 3) and 10 mg/kg (n = 6) every 3 weeks (Q3W) combined with CAPOX and Sintilimab. In expansion, all pts received ASKB589 IV at a dose of 6 mg/kg. Results: As of July 20, 2023, 9 pts were enrolled in escalation. No DLT was observed and thus the MTD was not identified. 9(100%)pts had treatment-related adverse events (TRAEs), the most common being nausea (77.8%), hypoproteinemia (66.7%), and hyponatremia (55.6%). While the majority of

322 Poster Session

A randomized phase III study comparing 2-weekly docetaxel, cisplatin and 5-FU (bDCF) with cisplatin and 5-FU (CF) in patients with metastatic or recurrent esophageal cancer: JCOG1314 (MIRACLE). First Author: Takahiro Tsushima, Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan Background: For metastatic or recurrent esophageal cancer, 2-drug combination of cisplatin and 5-FU (CF) has long been a standard of care before the emergence of immune checkpoint inhibitors (ICIs). Previous phase I/II study of 3-drug combination, 2weekly docetaxel plus CF (bDCF) showed promising antitumor activity (JCOG0807). We conducted JCOG1314, a randomized phase III study to confirm the survival superiority of bDCF over CF. Methods: Main eligibility criteria were metastatic or recurrent esophageal cancer; histologically proven squamous cell carcinoma or adenocarcinoma; age 20 to 75; no previous systemic therapy for metastatic disease. Patients were randomly assigned to CF arm (cisplatin 80 mg/m 2 on day 1, and 5-FU 800 mg/m 2 on days 1-5, every 28 days), or bDCF arm (docetaxel 30 mg/m 2 on day 1 and day 15 in addition to CF, every 28 days). The primary endpoint was overall survival (OS). Patients received fruquintinib (3mg, 4mg, 5mg, d1-d14, q3w, respectively), in combination with S-1 (40mg, 50mg, 60mg, bid, d1-d14, q3w, based on body surface area (BSA)), until unacceptable toxicities, progressive disease, or death. The initial fruquintinib dose was 4 mg d1-d14, q3w, in combination with an appropriate S-1 dose. Additional patients were enrolled in the dose-expansion phase and received the maximum tolerated dose determined in the dose-finding phase. Results: As of August 1, 2023, seven patients were enrolled in the dosefinding phase. One patient withdrew consent during the DLT assessment period. Among the patients administered a 4mg dose of fruquintinib, one out of three achieved a confirmed partial response (PR) after 7 cycles of treatment. Additionally, two out of three patients at the 5mg dose level achieved PR after 2 cycles of treatment, resulting in an overall response rate (ORR) of 50% (3/6). The disease control rate (DCR) was 100% (6/6). The median progression-free survival (PFS) was observed to be 4.93 months (95% CI: 1.93 -10.73), with overall survival (OS) at 10.73 months (95% CI: 2.1 -10.73). In terms of safety, no doselimiting toxicities (DLTs) were reported at 4mg dose level. While DLTs were observed in two out of the three patients at the 5mg dose level. The most common treatment-related adverse events (TRAE) across all grades were fatigue (5/7) and extremity pain (4/7). Grade 3 TRAE were identified in 5 patients, with hypertension (2/7), mucositis (2/7), and fatigue (2/7) being reported. No grade 4 or higher TRAEs were observed. Conclusions: Potential benefits were demonstrated when using fruquintinib in combination with S-1 for the treatment of ESCC patients after immunotherapy failure. The efficacy and safety of fruquintinib and S-1 will be further investigated in this trial later.

326 Poster Session

FRONTiER: A feasibility trial of nivolumab with neoadjuvant CF or DCF, FLOT therapy for locally advanced esophageal carcinoma (JCOG1804E)-Primary safety and short-term efficacy results for cohort E. First Author: Takako Yoshii, Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan Background: The standard neoadjuvant treatment in Japan for resectable locally advanced esophageal squamous cell carcinoma (ESCC) is DTX + CDDP + 5-FU (DCF). In addition, immune checkpoint inhibitors (ICIs) have shown a survival benefit for ESCC and are promising as neoadjuvant treatment for several cancers. We previously reported that neoadjuvant CDDP + 5-FU + nivolumab (Nivo) or DCF + Nivo therapy was tolerable and showed promising efficacy for ESCC. However, the efficacy of neoadjuvant treatment and safety of subsequent surgery remain unclear for 5-FU + l-LV + L-OHP + DTX (FLOT), the global standard of care for perioperative esophagogastric adenocarcinoma, plus ICI for ESCC. Methods: JCOG1804E (FRONTiER) is a multi-cohort phase I study designed to evaluate the safety and efficacy of Nivo combined with neoadjuvant chemotherapy in ESCC.

The eligibility criteria were histologically proven ESCC staged as cT1N1-3M0 or cT2-3N0-3M0 (8th UICC TNM classification), age 20-75 years, performance status (PS) #1, and no prior cancer therapy. The primary endpoint was the incidence of dose-limiting toxicity (DLT) from the initial dose to postoperative day 30. The secondary endpoints included adverse events during the perioperative period and at 30 days and the objective response rate, R0 resection rate, histopathological complete response rate, and completion rate of the protocol treatment including planned chemotherapy as below followed by R0 resection. Among five study cohorts, patients in cohort E were planned to receive four courses of FLOT+Nivo-5-FU (2600 mg/m 2 ), l-LV (200 mg/m 2 ), L-OHP (85 mg/m 2 ), DTX (50 mg/m 2 ), and Nivo (240 mg)-on day 1 every 2 weeks. Results: Pts with advanced G/GEJ cancer who had been exposed to ICIs before the second line were eligible. 42 pts would receive 100g/m 2 nab-paclitaxel on day 1 and day 8 every 3 weeks, and 4mg fruquintinib from day 1 to day 14 every 3 weeks. Progression-free survival (PFS) was set as the primary endpoint. The Kaplan-Meier method would be used to evaluate time-to-event outcomes. Results: Up to Aug 10, 2023, 25 pts had been enrolled, 23 of whom were evaluable. 14 (60.9%) pts in evaluable set were male. All these pts was with stage Ⅳ of TNM staging. The median age was 58 (range: 33-74), and 6 (26.1%) pts were elder than 65 yr. 12 (63.2%) pts were with PD-L1 CPS greater than 1, 9 (47.4%) pts greater than 5, and 4 (17.4%) pts greater than 10. PD-L1 CPS of 4 pts was unknown. The pts had received a median of 5 (range: 1-20) cycles in early-line ICI therapy. 17 (73.9%) pts suffered metastasis in retroperitoneal lymph node and 7 (30.4%) pts in liver. With a median follow up time of 5.6 (range: 2.1-16.6) mo, the PFS achieved 4.8 (95% CI: 4.6-NA) mo. Despite the immatureness of overall survival (OS), the 1-year OS rate was 56.25% (95% CI: 17.27%-95.23%). The ORR was 47.8% (n=11), and DCR was 100% (n=23). As to safety, the most common ($20%) AEs of all grades were white blood cell decrease, peripheral sensory neuropathy, and neutrophil count decrease, while that of grade$3 was white blood cell decrease. Conclusions: Fruquintinib with nabpaclitaxel as second-line therapy demonstrated good efficacy and safety in advanced G/GEJ cancer after exposure to ICIs. ICIs might increase benefit from this therapy, which warrants further investigations in a large cohort. Clinical trial information: ChiCTR2200059976. Research Sponsor: Chinese Society of Clinical Oncology.

328 Poster Session

Chemotherapy and chemoradiotherapy for adenocarcinoma of the esophagus and junction with oligometastases: Results of the TNT-OES-1 trial. First Author: Charlène J. van der Zijden, Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, Netherlands Background: Chemotherapy (FLOT) and chemoradiotherapy (CROSS) are effective as neoadjuvant regimens for esophageal and junction cancer. Total Neoadjuvant Therapy (TNT) aims to increase efficacy by combining chemotherapy with chemoradiotherapy.

Although TNT is increasingly used in rectal cancer, there are no data on combining FLOT and CROSS in esophageal cancer. This study aimed to evaluate the feasibility and safety of the FLOT-CROSS combination in esophageal and junction adenocarcinoma patients with oligometastatic disease. Methods: This phase-II study included patients with oligometastatic (a maximum of four lesions in up to two organs, excluding lymph nodes) esophageal adenocarcinoma. Patients were treated with four biweekly cycles of FLOT. Response was evaluated by CT-scan 4-6 weeks after completion of FLOT. If patients showed regression or stable disease (SD) based on RECIST criteria (v1.1), they received CROSS. Four to six weeks after completion of CROSS, response was assessed by CT-scan, endoscopy with biopsies and endoscopic ultrasonography. The multidisciplinary tumor board discussed whether patients could proceed to four additional cycles of FLOT or local therapy of metastases and/ or esophagectomy. Primary endpoint was tolerability of FLOT-CROSS, defined as the proportion completing the full regimens. Secondary endpoints included disease control rate (DCR), objective response rate, toxicity and the proportion proceeding to local therapy of metastases and/or esophagectomy. Results: Twenty patients were included, the majority was male (85%) with a median age of 62.5 years (interquartile range 58-66) Most patients (80%) had a single metastatic lesion. 14 of 20 patients (70%) successfully completed the FLOT regimen, four are still in therapy and two patients died. Eleven of 14 patients completed FLOT-CROSS and three patients showed disease progression following FLOT. Toxicity mainly consisted of grade 1-2 leukopenia/neutropenia during FLOT, leading to treatment delay in seven patients. One patient had malaise grade 2. No grade 3-4 toxicities or treatment delays/discontinuations occurred during CROSS. Following FLOT-CROSS, seven patients underwent four additional cycles of FLOT. Six patients underwent esophagectomy and two of those also underwent local treatment of metastases. A pathologically complete response was seen in two of these six patients (33%). Three of seven patients had a clinically complete response and opted for active surveillance after shared decision making. Three months after completion of FLOT-CROSS, the DCR was 82%.

Conclusions: This study showed that sequencing FLOT-CROSS in patients with oligometastatic esophageal adenocarcinoma is feasible and comes with manageable toxicity. We saw promising efficacy, with 82% having disease control three months after FLOT-CROSS.

Survival data are expected mid-2024. Clinical trial information: NL9269. Research Sponsor: None.

The overall safety and short-term efficacy of nivolumab plus ipilimumab for advanced esophageal squamous cell carcinoma. First Author: Kazuhiro Shiraishi, National Cancer Center Hospital, Chuo-Ku, Tokyo-to, Japan Background: Although nivolumab plus ipilimumab (Nivo+Ipi) is strongly recommended as 1st-line treatment for patients with advanced esophageal squamous cell carcinoma (ESCC), tumor proportion score (TPS) should be considered. Despite the efficacy, patients who received Nivo+Ipi often experienced serious immune related adverse events (irAEs). However, there are few data on safety and short-term efficacy of Nivo+Ipi in real world. Methods: We retrospectively collected data of pts who received Nivo+Ipi for advanced ESCC between May 2022 to July 2023 in the National Cancer Center Hospital. We evaluated adverse events by CTCAE v5.0 and multivariate analysis using a logistic regression model. estimated overall response rate (ORR) by RECIST v1.1 and progression-free survival (PFS). Results: Thirty pts were subjects in this study. The characteristics were as follows: median age (range): 63.5 (36-80) years, male/female: 24/6, metastatic/recurrent: 3/27, ECOG PS 0/1#: 16/14, PD-L1 TPS 1%#: 17, number of organs with metastases 1/2#: 13/17, treatment-line 1st/2nd# 6/24 Median follow-up time was 5.0 months (mo) (reverse Kaplan-Meier, 95%CI; 3.0-8.3 mo). Any grade and grade 3# irAEs were observed in 12 (40.0%) and in 5 pts (17.9%), respectively. In grade 3# irAEs, AST/ALT elevation (n=2, 7.1%), adrenal insufficiency (n=1, 3.6%), pneumonitis (n=1, 3.6%), myositis (n=1, 3.6%), encephalopathy (n=1, 3.6%), stevens-Johnson syndrome (n=1, 3.6%) were reported. The pts who received systemic steroid therapy was 8 pts (28.6%). Two pts received high-dose steroid with methyl-prednisolone, 1 g/body for 3 days, four pts needed steroid therapy with prednisolone, 1-2 mg/kg and two pts added mycophenolate mofetil. No treatment-related deaths were reported. For the pts who received Nivo+Ipi as a first-line treatment (n=6), 3 pts (50%) achieved partial response and 2 pts (33.3%) had stable disease. 6-mo PFS rate of the 1st line pts was 63%. For the pts who received Nivo+Ipi in later-line, the ORR and the median PFS were 33.3% and 2.6 mo (95%CI; 1.4-3.9 mo), respectively. Fifteen pts received subsequent systemic therapy, which consisted of taxane ( 12

332 Poster Session

Fruquintinib combined with sintilimab as a second-line therapy for advanced gastric and gastroesophageal junction adenocarcinoma (GC/ GEJC): A phase II, single-arm, prospective study. First Author: Min Jin, Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China Background: The KEYNOTE-061 trial showed that anti-PD-1 monotherapy did not improve overall survival compared to chemotherapy in the second-line treatment of advanced GC/ GEJC. Preclinical and clinical data have demonstrated the synergistic anti-tumor effect of fruquintinib, a highly selective oral VEGFR 1/2/3 inhibitor, in combination with immune checkpoint inhibitors (ICIs). Additionally, the phase III study (NCT03223376) of fruquintinib combined with paclitaxel in second-line GC/GEJC has yielded positive topline results. This study aims to assess the safety and efficacy of fruquintinib combined with sintilimab (an anti-PD-1 antibody) as a second-line therapy for GC/GEJC. Methods: In this phase II, openlabel trial (NCT05625737), patients (pts) aged 18-75 years who were HER2-negative and had failed first-line standard therapy were enrolled. Eligible pts received fruquintinib at 4mg/day orally on days 1-14 and sintilimab at 200 mg intravenously on day 1, with treatment repeated every 3 weeks. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. An optimal Simon two-stage design was employed: if more than 1 pt achieved objective responses in the first stage (n = 7), the study would proceed to the second stage and enroll an additional 19 pts; otherwise, the study would be terminated.

Results: At data cut-off (August 31, 2023), 7 pts were enrolled in the first stage and additional 7 pts in the second stage. Pts characteristics included: median age 50 (range 33-71); 29% male; 57% with ECOG PS 1; 57% with peritoneal metastasis, and 71% having previously received immunotherapy. Of the 12 pts evaluable for tumor response, 4 achieved partial responses, and 4 had stable disease, resulting in a confirmed ORR of 33.3% (95% CI: 9.9-65.1%) and a DCR of 66.7% (95% CI: 34.9-90.0%). The median PFS was 5.09 months (95% CI: 2.69-NA), while OS results were pending maturity. Grade 1-2 treatment-emergent adverse events (TEAEs) occurred in $20% of pts, including decreased white blood cell count (36%), hypertriglyceridemia (29%), abdominal pain (29%), decreased lymphocyte count (21%), and elevated aspartate transaminase and alanine transaminase (21%). Grade 3/4 TEAEs occurred in only one patient, consisting of increased blood bilirubin levels, aspartate transaminase elevation, and alanine transaminase elevation. No treatment-related deaths were reported. Conclusions: The combination of fruquintinib and sintilimab as a secondline therapy has demonstrated promising anti-tumor activity and an acceptable safety profile in pts with advanced GC/GEJC. The trial is ongoing, and further data analysis and reporting are anticipated. Clinical trial information: NCT05625737. Research Sponsor: None.

Clinical significance of time interval between surgery and adjuvant chemotherapy in patients with gastric cancer after gastrectomy: A populationbased cohort study using a nationwide claims database. First Author: Chi Hoon Maeng, Department of Medicine, Division of Medical Oncology-Hematology, Kyung Hee University Hospital, Seoul, South Korea Background: Adjuvant chemotherapy can reduce recurrence rates by eradicating microscopic metastases which may persist after curative resection. However, the optimal time interval (TI) between the surgery and chemotherapy remains controversial. Methods: The data were obtained from the NHIS of Korea. We included patients who underwent gastrectomy for gastric cancer between 2013 and 2018. To determine the optimal cut-off point of TI, a restricted cubic spline cox regression model was established, and categorized the population into three groups based on TI: the early group (# 20 days), the reference group (21-34 days), and the late group ($ 35 days) with the reference interval group having the lowest mortality and recurrence. Propensity score matching was performed for each group. The primary outcomes were disease-free survival (DFS) and overall survival (OS). Results: During the study period, 98,556 patients underwent surgery for gastric cancer. After excluding ineligible participants, 6,602 patients were included in the analysis. The median DFS and OS did not differ significantly between the early and reference groups (p=0.7258 and p=0.6056, respectively). In comparison between the late and reference groups, the median DFS was significantly lower in the late group (p=0.0079). 5-year DFS were 77.6% and 81.3% in the late and reference groups, respectively. Furthermore, the late group showed worse OS than the reference group (p=0.0336

339 Poster Session

Subgroup analyses of the effect of ramucirumab in pretreatment with immune checkpoint inhibitor in RINDBeRG: A randomized clinical trial in third-or further-line treatment of gastric cancer. First Author: Ryohei Kawabata, Osaka Rosai Hospital, and Sakai City Medical Center, Sakai, Osaka, Japan Background: To confirm synergistic effect of immune checkpoint blockade and antiangiogenesis in cancer treatment, we evaluated the effect of pretreatment with immune checkpoint inhibitors to ramucirumab plus irinotecan versus irinotecan in the third or later line treatment beyond progression after ramucirumab for advanced gastric cancer from the RINDBeRG trial. Methods: Patients received ramucirumab at 8 mg/kg plus irinotecan at 150 mg/m2 or irinotecan alone. End points were compared between treatment arms and pretreatments with nivolumab (NIVO+, n = 226) or without nivolumab (NIVO-, n = 169). Results: The overall survival hazard ratio was 0.84 (95 % confidence interval, 0.64-1.12) in the NIVO+ population and 1.05 (95 % confidence interval, 0.76-1.44) in the NIVO-population. The progression-free survival hazard ratio was 0.67 (95 % confidence interval, 0.51-0.87) in the NIVO+ population and 0.83 (95 % confidence interval,0.61-1.12) in the NIVO-population. The objective response rate was higher for ramucirumab plus irinotecan in both populations (NIVO+ population, 17.5 % vs 28.8 %; NIVO-population, 10.9 % vs 14.5 %). Safety profiles of the ramucirumab plus irinotecan arm were similar between populations. Conclusions: Progression-free survival and objective response rate improvements were observed for ramucirumab plus irinotecan in both populations and these benefits were enhanced with prior nivolumab therapy. Clinical trial information: jRCTs051180187

342 Poster Session

A retrospective analysis of the efficacy and safety of capecitabine plus oxaliplatin (CapeOX) and docetaxel plus S-1 (DS) as adjuvant chemotherapy for pathological stage III (p stage III) gastric cancer (GC). First Author: Toru Imai, Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan, Chuo City, Tokyo, Japan Background: Adjuvant chemotherapy following surgical resection is the standard treatment for patients with p stage III GC in Japan. Although CapeOX and DS are available for adjuvant chemotherapy for stage III GC, there is limited data on which treatment is more effective. We aim to compare the efficacy and safety of CapeOX and DS as adjuvant chemotherapy in patients with p stage III GC. Methods: We extracted data of patients with p stage III GC who received either CapeOX (capecitabine on days 1-14 plus oxaliplatin on day1 for 8 cycles [q 3week]) or DS (S-1 on days 1-14 at 1 st cycle [q 3 week] , docetaxel on day 1 plus S-1 on days 1-14 during 2-7 cycles [q 3 week], and S-1 on days 1-28 up to 1 year [q 6 week] ) as adjuvant chemotherapy after surgical resection at our institution from February 2016 to May 2022. Three-year relapse-free survival (RFS) and adverse events (AEs) were assessed. Cox proportional hazard model was used in multivariable analysis to assess the effect of independent variables on RFS.

Results Background: Immunotherapy has improved survival for patients with advanced esophageal squamous cell carcinoma (aESCC) and currently is the standard of care for patients with a positive PD-L1 status (CPS $10; TPS $1%) in the first-line setting. For PD-L1 negative/low, treatment options are limited, and chemotherapy is usually the first choice and associated with adverse events that may impair quality of life. Immunotherapy trials harbor conflicting results in this subgroup of patients, therefore, we performed a systematic review and meta-analysis to evaluate the potential benefit of ICI as single treatment for patients with aESCC and a PD-L1 expression negative/low. Methods: Studies that enrolled patients with aESCC treated with ICI versus chemotherapy in first and second-line settings and provided separate outcomes for patients with PD-L1 negative/low were identified by searching the EMBASE, PubMed and Cochrane databases. The outcomes evaluated were Overall Survival (OS), Progression Free-Survival (PFS) and Treatment-Emergent Adverse Events (TEAE). We pooled hazard ratio (HR) for PFS and OS endpoints and odds ratio (OR) with 95% confidence intervals (CI) for TEAE. Statistical analyses were performed using Revman 5.4 and a randomeffects model. I² analysis was used to assess heterogeneity. This meta-analysis was recorded on Prospero ID CRD42023411251. Results: We included 6 randomized clinical trials with a total of 674 individuals in the final analysis. Most studies (5/6) included previously treated patients. ICI monotherapy in aESCC patients and PD-L1 expression negative/low was associated with a better OS (HR 0.86; 95% CI 0.76-0.97; p = 0.02; I² = 0%) and worse PFS (HR 1.37; 95% CI 1.10-1.71; p = 0.005; I² = 0%). Regarding the safety profile, it showed higher grade 3-5 toxicity rates (OR 1.8; 95% CI 1.17-2.78; p = 0.007; I² = 85%) for chemotherapy. Conclusions: ICI is effective for patients with aESCC and low/ negative PD-L1 expression with an improvement in OS and a favorable safety profile.

347 Poster Session

Anlotinib plus TQB2450 as adjuvant therapy in patients with esophageal squamous cell carcinoma: A phase II study (ALTER-E005). First Author: Changying Guo, Jiangxi Provincial Tumor Hospital, Nanchang, China Background: There is currently a limited range of therapeutic options available for postoperative patients (pts) with esophageal squamous cell carcinoma (ESCC), emphasizing the urgent requirement to investigate more efficient and safer postoperative treatment regimens for resectable ESCC. TQB2450, a novel PD-L1 blockade, has shown promising activity when combined with anlotinib, an antiangiogenic agent, in the treatment of various tumors, including advanced ESCC, 1 and biliary tract cancer. 2 The ALTER-E005 study aimed to evaluate the efficacy and safety of combining anlotinib with TQB2450 as adjuvant therapy in pts with ESCC. Methods: This was a single-arm, multicenter phase II clinical trial. 30 pts ($18 years) with histologically confirmed T1-2N1-3M0 or T3-4NanyM0 ESCC who had undergone radical (R0) resection with no recurrence 6 to 12 weeks after surgery and ECOG PS # 1 would been rolled. Enrolled pts received oral anlotinib 12 mg on days 1-14 and intravenous TQB2450 1200 mg on day 1every 3 weeks for up to 16 cycles, until disease recurrence. The primary endpoint was disease recurrence free (DFS).

397 Poster Session

Prognostic role of platelet-to-lymphocyte ratio (PLR) and neutrophil-tolymphocyte ratio (NLR) in advanced gastric cancer treated with immunotherapy: A systematic review and meta-analysis. First Author: Silvio Matsas, Faculdade De Ciencias Medicas Da Santa Casa De S ão Paulo, S ão Paulo, Brazil Background: Recent advances in the treatment of Gastric Cancer (GC) have introduced immunotherapy as a promising approach for advanced disease. In this context, potential biomarkers such as the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) have gained attention for their roles in predicting treatment outcomes. In this meta-analysis, we explore the clinical significance of PLR and NLR as predictors of Overall Survival (OS) and Progression-Free Survival (PFS) in advanced GC patients undergoing immunotherapy. Methods: Two independent reviewers systematically searched electronic databases, including PubMed, Embase and Scopus. The search incorporated controlled vocabulary (MeSH terms) and keywords related to Gastric Cancer, immunotherapy, platelet-to-lymphocyte ratio (PLR), and neutrophil-tolymphocyte ratio (NLR). Eligible studies were selected based on predefined criteria, including HR availability, and were assessed for quality and bias using the Newcastle-Ottawa Scale. Data extraction was independently performed by two reviewers, and discrepancies in study selection and data extraction were resolved by a third reviewer. Subgroup analyses were performed to explore potential variations in the study outcomes. All analyses were conducted with RevMan 5.4 and employed random-effects model. Results: In total, 16 studies encompassing 1176 patients for NLR and 8 studies covering 766 patients for PLR were included in this systematic review and metaanalysis. The studies spanned the years between 2018 and 2023. Our analysis revealed significant associations between high NLR and poor OS (HR: 2.11, 95% CI: 1.70-2.62, p , 0.00001) and PFS (HR: 1.76, 95% CI: 1.43-2.17, p , 0.00001). Similarly, elevated PLR was significantly associated with worse OS (HR: 1.77, 95% CI: 1.44-2.17, p , 0.00001) and PFS (HR: 1.61, 95% CI: 1.33-1.96, p , 0.00001). In all conducted subgroup analyses, high NLR and PLR were consistently associated with poor survival outcomes. Conclusions: Our analysis supports the significance of NLR and PLR as accessible and cost-effective biomarkers for predicting survival outcomes in the context of immunotherapy for advanced GC. These findings underscore their potential significance in guiding clinical decisions. Further investigation should be carried out to validate our findings. Research Sponsor: None.

Treatment development targeting Hippo pathway for scirrhous type gastric cancer. First Author: Yuichiro Miki, Department of Gastroenterological Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan Background: Treatment outcome of gastric cancer (GC) has been improved by minimally invasive surgery, and development of new drugs including immune checkpoint inhibitors. However, survival for patients with scirrhous type (SGC, Type4) gastric cancer is dismal. Methods: We collected miRNAs form exosomes released from cancer associated fibroblasts which is developed from resected gastric cancer tissue. Pathway enrichment analysis (PEA) of top miRNAs showed that they are significantly associated with Hippo signaling pathway (Hippo pathway). The molecules relating Hippo pathway was evaluated by Western blotting in cell line, and IHC of tissue array. Results: PEA using top miRNAs showed the significant relationship to Hippo pathway. Yap is a final effector in this pathway, and we found that YAP is not expressed in MKN45 cells (diffuse type), which is supposed to be degraded in cytoplasm. On the contrary, MKN74 cells express both YAP and pYAP. IHC showed that YAP translocation to nucleus is significantly associated with CTGF expression. CTGF low expression is significantly associated with worse prognosis especially in diffuse type GC (Log rank p = 0.022). This trend is similar in the analysis of patients with SGC. Conclusions: The role of Hippo pathway is different between intestinal type and diffuse type of GC. YAP activator could be effective for the treatment of SGC, and we are focusing on the treatment development. Research Sponsor: JSPS-KAKENHI.

399 Poster Session

Gastric microbiome signature to predict metachronous recurrence after endoscopic resection of gastric neoplasms. [10] ; 60%) patients were identified. The majority (.70%) of samples were obtained from primary sites. Adenocarcinoma was the most common histological type for GC (85%) ad PC (76%), while squamous cell (76%) was the most common among EC patients. In the GC cohort, the prevalence of key actionable genomic alterations in J-SCRUM GI-SCREEN vs TCGA (N = 380) was, TP53 mutation (49% vs 49%), ERBB2 amplification (14% vs 13%), PIK3CA mutation (11% vs 14%), MYC amplification (9% vs 12%) and MET amplification (2% vs 3%). In the EC cohort, the prevalence in J-SCRUM vs TCGA (N = 182) was TP53 mutation (77% vs 87%), NFE2L2 mutation (21% vs 10%), PIK3CA mutation (9% vs 9%) and CDKN2A mutation (8% vs 8%). In the PC cohort, the prevalence in J-SCRUM vs TCGA (N = 150) was KRAS hotspot mutation (90% vs 93%), KRAS G12D (43% vs 41%), KRAS G12V (32% vs27%), TP53 mutation (58% vs 64%), BRCA1/2 deleterious mutation (5% vs 5%), ATM deleterious mutation (6% vs 5%) and MYC amplification (5% vs 5%).

Conclusions: As part of a nationwide cancer genome screening project, J-SCRUM GI SCREEN database provides comprehensive genomic information for Asian population (Japan). The prevalence of key actionable gene alterations in each tumor type was highly comparable between J-SCRUM GI-SCREEN and TCGA data. Research Sponsor: Merck & Co., Inc.

402 Poster Session

Real world prevalence of biomarkers for treatment of advanced gastric cancer or gastroesophageal junction cancer in a cohort of Colombian patients. First Author: Diego Felipe Ballen, Instituto Nacional de Cancerología, Bogotá, Colombia

Background: Gastric cancer (GC) is the leading cause of cancer-related deaths in Colombia, GLOBOCAN estimated 6.451 deaths in 2022. Development of immune checkpoint inhibitors and HER2 target therapy with chemotherapy had improved overall survival in advanced setting, but we do not have data about the prevalence of biomarkers used for selection of these patients in Colombia or Latin-America. Our aim is to describe the prevalence of biomarkers used currently for selection of treatment in a real-world multicenter cohort of advanced gastric and gastroesophageal junction (GEJ) cancer. Methods: We did a retrospective observational multicenter study of patients with advanced GC/GEJ cancer treated at three reference cancer centers in Bogota, Colombia between January 1, 2023 and July 31, 2023. We reviewed medical history and pathology reports looking for the prevalence of biomarkers used for selection of first line systemic therapy. Ventana 4B5 for HER2 IHQ evaluation and Dako 22C3 for PDL1 expression by CPS were used. MMR proteins were evaluated by IHQ nuclear expression. Results: 101 patients with advanced GC/GEJ were included. The median age was 61 years (range 18-83), 53,5% of patients were men, 92.1% were gastric cancer and 87,1% were de novo stage IV. Signet ring cells were found in 40%, peritoneal carcinomatosis was documented in 59% and 75,2% were distal tumors (no cardias or GEJ involvement). PDL1 positivity, defined as CPS $1 was found in 30.6%, using CPS $ 5 cutoff just 22.7% of them were positive. HER2 positivity and MMR deficiency were found in the same proportion of patients 5%. Among young patients (, 50 years) 80% had diffuse histology, 30% were CPS $5. HER2 status and PDL1 testing was unknown in 21% and 29% respectively. Conclusions: Among these real-world patients, both HER2 and PDL1 positivity was lower than reported in other regions. Higher incidence of distal tumors, signet ring cells and diffuse histology could explain this difference. Correlation of PDL1 positivity between 22C3 and 28.8 was unknown in our population. Our study remarks the high medical need for investigation of biomarkers and developing of prospective studies for correlation and other targets like Claudins and FGFR2b. Research Sponsor: None.

Demographics and disease characteristics.

Characteristic All Patients 101

Ageyr, median (range)

405 Poster Session

The distribution of human epidermal growth factor receptor 2 (HER2) expression and the efficacy and safety of treatments in HER2-expressing advanced or metastatic gastroesophageal cancer: A systematic literature review (SLR). First Author: David Bing Zhen, University of Washington Fred Hutchinson Cancer Center, Seattle, WA Background: HER2 overexpression plays an important role in determining treatment options for patients with gastroesophageal cancer (GEC). HER2 overexpression has historically been defined dichotomously as HER2-positive (HER2+) or HER2-negative. An emerging potentially clinically relevant category is HER2-low, which could be targeted with HER2-directed antibody drug conjugates. However, data on the epidemiology and outcomes associated with HER2-low GEC are limited. Methods: An SLR of PubMed, Embase, and Cochrane Central Register of Controlled Trials databases was conducted to identify clinical trials, observational studies, and meta-analyses reporting clinical outcomes or distribution of HER2 expression by IHC and ISH in advanced or metastatic (a/m) GEC. Key inclusion criteria were: English language, published between 2013-2023, and sample size $100 HER2-expressing patients. HER2+ was defined as IHC score of 3+ or IHC 2+ and ISH+. HER2-low was defined as IHC 1+ or IHC 2+ and ISH-. Weighted averages were calculated for the proportion of patients who were HER2+ and HER2-low to estimate of the proportion of patients in each HER2 expression category. Results were categorized by patient population (all GEC or gastric cancer [GC] only). Results: Of 2,701 non-duplicated records screened, 174 studies met inclusion criteria. Distribution of HER2 expression was reported in 111 studies, 5 of which reported on the frequency of HER2 expression of IHC 1+ and/or IHC 2+ and ISH+. HER2 expression status varied by patient population, with a weighted average of 26.9% for HER2-low and 13.1-16.5% for HER2+ across groups (Table ). Different cutoffs for HER2 amplification via ISH also affected the proportion of patients in each HER2 category across studies. Efficacy and safety outcomes were stratified by HER2 status or IHC results in 74 studies. However, only 3 observational studies reported outcomes separately for the HER2-low population, and results were inconclusive.

The distribution of HER2 expression in a/m GEC in the identified studies is highly heterogenous, likely due to variability in IHC scoring and patient populations. Few studies with sufficient samples size ($100 patients with HER2-expression a/mGEC) reported outcomes for HER2-low a/m GEC, and those that were identified were of low quality. The HER2-low a/m GEC population constitutes an unmet need for effective therapy. There is a need for consistent use of a standardized definition of HER2-low in a/mGEC and additional studies to better evaluate treatment options and outcomes for this patient population. Research Sponsor: None.

Weighted average prevalence of HER2 expression status.

HER2 Status

409 Poster Session

Noninvasive assessment of programmed-death ligand-1 (PD-L1) in esophagogastric (EG) cancer using 18 F-BMS-986229 PET. First Author: Samuel Louis Cytryn, Memorial Sloan Kettering Cancer Center, New York, NY Background: PD-1 inhibitors are now standard in advanced EG cancer, with approval often based on PD-L1 CPS. However, single site biopsies are inadequate due to disease heterogeneity, dynamic changes over time, and variability due to operator, choice of assay, and tumor content. Better methods of non-invasive, comprehensive PD-L1 evaluation are needed. Methods: This is a prospective, pilot PET study of the positron-emitting agent 18 F-BMS-986229, a macrocyclic peptide with high affinity for PD-L1. Patients were administered 18 F-BMS-986229 intravenously and underwent whole body PET/CT 60 minutes later. The primary endpoint was safety and feasibility. Results: Ten patients underwent PD-L1 PET imaging. All had adenocarcinoma, 70% had metastatic disease, 20% had locally advanced, unresectable tumors, and 10% had resectable tumors. 30% of patients received prior treatment, including 2 with a PD-1 inhibitor. Median PD-L1 CPS was 10 (IQR 5-20). No patients experienced an adverse event associated with 18 F-BMS-986229. Although PD-L1 CPS $1 was required for inclusion, 2 patients who had PD-L1 CPS $1 on initial biopsy, had a subsequent biopsy closer in time, but still prior to PD-L1 PET imaging, with PD-L1 CPS ,1. In 8 of 10 patients, the biopsy site was evaluable by PD-L1 PET imaging. 5 of the 6 biopsy sites that were PD-L1 CPS $1, were PD-L1 PET avid; both biopsy sites that were PD-L1 CPS ,1 were appropriately non-avid. In sum, 88% of patients had radiographic and pathologic concordance. The Spearman rank correlation coefficients (r s ) between PD-L1 CPS and PD-L1 PET visualization score (scored 1 to 5, defined by accumulation greater than adjacent background) was 0.64, and 0.61 between PD-L1 CPS and PD-L1 PET SUV. Patients with a higher PD-L1 PET visualization score had a higher PD-L1 CPS: those with a maximum visualization score of 5 (n=4), had a median PD-L1 CPS of 22.5 (range 5-70), those with a maximum score of 4 (n=2) had PD-L1 CPS of 5 and 20, and those without any avid lesions (score of 3 or lower) had a median PD-L1 CPS of 5 (range 0-10). 71% of patients with PD-L1 PET avid lesions, also had non-avid sites of disease, 80% of whom had a more than 2-fold difference in SUV between the most and least avid lesions. 7 patients had untreated, advanced disease, 6 of whom were treated with PD-1 inhibitors as frontline therapy. 3 had PD-L1 PET avid lesions: 2 achieved a complete response (CR), the third achieved a partial response (PR), and progression free survival (PFS) was 32, 28, and 22 months respectively. Among the 3 patients with non-avid PD-L1 PET imaging who received PD-1 inhibitors as frontline therapy, 1 achieved a CR, 1 achieved a PR, and 1 had progressive disease, with PFS of 14.5, 10, and 2 months, respectively. Conclusions: We report the first use of PD-L1 PET imaging in patients with EG cancer and demonstrate its potential use as a companion diagnostic tool to aid in identifying patients who may benefit from PD-1 therapy. Clinical trial information: NCT04161781. Research Sponsor: Bristol Myers Squibb.

410 Poster Session

Survival after esophagectomy for metastatic esophageal cancer: Should surgery's role be reconsidered? First Author: Samir H Saeed, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL Background: Standard treatment for stage IV esophageal cancer (EC) is systemic therapy, with surgery considered contraindicated. The objective of this study is to assess the impact of surgical resection on outcomes for patients with metastatic EC. Methods: We reviewed our institution's IRB-approved database of 1334 esophagectomies from 1994 to 2023 and identified 18 patients with distant disease (stage IV) by AJCC8 found prior to or during surgery. Chi-Square, ANOVA, and Kaplan-Meier survival analyses were used to compare demographics, clinical characteristics, and survival from time of surgery in those with metastatic versus non-metastatic EC. Results: Most metastatic patients were male (89%), Caucasian (83%), and had adenocarcinoma (89%).

Compared to the non-metastatic cohort, stage IV EC cases were younger (57 vs 63; p=0.03), non-Caucasian (17% vs 6%; p=,0.001), and more likely to get chemotherapy (41% vs 8%; p=0.04) or immunotherapy (23.5% vs 0%; p=0.06), with no difference in gender (89% vs 83%) and receipt of chemoradiotherapy (94% vs 92%). While the difference in intra-operative complication rates was significant (13% vs 2%; p=0.001), both groups had similar rates of post-operative complications (p=0.95). Non-regional nodal metastasis had the most favorable outcome (mOS NR; median follow-up=14m); while peritoneal/omental disease had the shortest survival (5.2m). Patients receiving surgery more than a year after stage IV diagnosis (n=6) had better survival than those who either underwent resection within a year after diagnosis (n=2) or had metastasis identified at time of surgery (n=8) (p=0.02). PDL-1 positive and HER2-neu positive tumors also had better outcomes, with neither group reaching median survival.

Conclusions: Esophagectomy for highly selected patients with distant disease demonstrates similar post-operative complication rates to locally advanced EC. For stage IV patients, a short interval from diagnosis to surgery is associated with worse survival; however, prolonged diagnosis-to-surgery interval .12m and PDL-1 and HER2-neu positivity demonstrate better outcomes. Surgery's role in treatment of stage IV EC preferably more than a year after diagnosis of metastasis should be further studied.

Correlation between postoperative systemic inflammatory response and prognosis in patients with advanced gastric cancer. First Author: Kenji Kuroda, Department of Gastroenterological Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan Background: Several studies have shown that postoperative infectious complications correlate with poor prognosis in various malignancies, but the prognostic significance of the postoperative inflammatory response in patients with gastric cancer remains unclear. The aim of study was to examine whether the systemic inflammatory response present in the early phase of the postoperative state correlates with long-term outcomes and to identify markers in patients with advanced gastric cancer. We evaluated Creactive protein (CRP) and white blood cell (WBC) count as simple and versatile markers of postoperative systemic inflammation in clinical practice that may be suitable for detecting the magnitude of inflammatory reaction. Methods: This study retrospectively reviewed 444 patients who underwent radical gastrectomy for stage II/III gastric cancer.

We evaluated maximum serum C-reactive protein (CRPmax) and white blood cell count (WBCmax), defined as the maximum serum CRP level and maximum WBC count during the interval from surgery until discharge, as systemic inflammation markers. Results: In univariate analyses, CRPmax, WBCmax and infectious complications were significantly associated with both overall survival (OS) (p,0.001, p,0.001 and p=0.011, respectively) and relapse-free survival (RFS) (p,0.001, p=0.001 and p,0.001, respectively). Multivariate analysis revealed that high CRPmax (.9.2 mg/dL) was an independent prognostic factor for OS (hazard ratio (HR) 1.69, 95% confidence interval (CI) 2000-2004; 2005-2009; 2010-2014; and 2015-2017) . x2 test was performed between two specified periods (2000-2004 and 2015-2017) to compare categorical variables. Overall survival (OS) curves were stratified by four separate periods and compared with log-rank tests. Results: The current analysis comprises a retrospective cohort of 1406 patients (552 female and 854 male individuals). Across all periods, most patients were men aged 50 to 69 and presented with Lauren's intestinal subtype. There were significant differences between staging groups during the study. Specifically, between 2000-2004, stage IV varied from 43.6% to 32.8% in 2015-2017 (P,0.001). The most substantial variation in nonmetastatic cases occurred in stage II, comprising 9.4% of cases from 2000-2004 and rising to 24.8% in 2015-2017 (P,0.001). Concerning treatment modalities, we observed an increased utilization of a combined approach involving chemotherapy and surgery throughout the investigation. Specifically, from 2000-2004, only 12% of patients received a multimodal treatment regimen consisting of chemotherapy and surgery, whereas, between 2015-2017, this proportion increased to 36.3% (P,0.001). Also, patients receiving surgery + radiotherapy + chemotherapy varied from 12.4% of patients in 2000-2004 to 4.5% in 2015-2017 (P,0.001). When the entire cohort was analyzed, the predicted 5-year OS of patients with GA between 2000-2004 was 27.8%, which increased to 53.9% in the period from 2015-2017 (P,0.001). Among females, 5-year OS increased from 31.3% between 2000-2004 to 58.5% between 2015-2017 (P=0.001). Among males, 5-year OS increased from 25.2% to 51.0% in the same comparison (P,0.001). Conclusions: Our hospitalbased data shows an upward trend in survival rates across patients with GA. We observed that 5-year OS almost doubled among men and women during the analyzed period. Recent improvements in staging methods and treatment have increased cure rates. Nevertheless, further investigation is essential to determine significant differences in OS between males and females. Research Sponsor: None.

414 Poster Session

Impact of primary prophylaxis (PP) with granulocyte colony-stimulating factor on the outcomes of patients with locally advanced gastric cancer treated with FLOT: A single-center retrospective analysis. First Author: Pedro Henrique Benfatti Gomes, AC Camargo Cancer Center, S ão Paulo, Brazil Background: The role of primary prophylaxis (PP) with granulocyte colony-stimulating factor (G-CSF) for patients with locally advanced gastric cancer (LAGC) treated with FLOT is currently unknown. Although original FLOT4 study did not recommend PP, the use of G-CSF is common in clinical practice to avoid serious complications. However, its use is associated with increased financial costs. Methods: This is a retrospective, single-institution study. We included patients with pathologically confirmed LAGC who received perioperative FLOT4. Patients were categorized in two groups: PP versus no-PP. Our objectives were to compare frequency of grades 3 or 4 neutropenia (G3/4N) and febrile neutropenia (FN) between PP and non-PP patients. We also evaluate the association between pathological complete response (pCR) and disease-free survival (DFS) and overall survival (OS) according to the use of PP. Binomial variables were compared using Fisher's exact test. Kaplan-Meier method was used to calculate median DFS and OS and respective 95% confidence intervals Methods: Data from 44 hospitals in China were collected using a designed CRF, comprising baseline, surgical details, pathology results and recovery progress from January 1,2020. Data cut-off was August 31, 2023. The study is ongoing. Results: A total of 1322 patients were enrolled, and only 946 patients with complete data were included in the analysis. The median age was 65 years (range, 24-90). Among them, 28 patients were classified as Siewert type I, 601 as type II, and 317 as type III. Laparoscopic surgery was performed in 845 patients, while 101 underwent open surgery, with no significant difference in postoperative complication rate between them. However, the laparoscopic group demonstrated superior favorable outcomes in terms of postoperative recovery times, with shorter postoperative exhaust time (3.0 days vs 3.6 days, p,0.001), feeding time (5.0 days vs 5.8 days, p=0.013), discharge time (11.6 days vs 14.6 days, p=0.002), as well as lower intraoperative blood loss (103.9 ml vs 163.4 ml, p=0.001). Among the patients, 891 underwent transhiatal approach, while 55 underwent thoracoabdominal approach, and no significant differences in postoperative complication rates, intraoperative blood loss and hospital stay were observed between these approaches. However, the transhiatal approach was associated with a shorter operative time ( 244

TPS416 Trials in Progress Poster Session

Protocol for open-label, randomised, controlled trial of intensive surveillance vs. standard postoperative follow-up in patients undergoing surgical resection for oesophageal and gastric cancer (SARONG trial). First Author: Sheraz Markar, University of Oxford, Oxford, United Kingdom Background: Despite recent improvements in oncological and surgical treatment for patients with oesophageal and gastric cancer, 60% of patients with locally advanced disease who are treated with a curative intent will develop tumour recurrence and die within three years of completing treatment. In the absence of robust scientific evidence national or international guidelines have failed to reach consensus on the optimal surveillance strategy after primary treatment of oesophageal or gastric cancer. Methods: The primary research question of the proposed randomised controlled trial (RCT) is does the routine use of a structured follow-up program with regular radiological and endoscopic investigations improve survival in patients who have had surgical treatment for oesophageal or gastric cancer with curative intent? We aim to assess whether structured follow-up, including radiological and endoscopic investigations after completing curatively intended treatment, improves survival in patients with oesophageal or gastric cancer. The secondary aims of this RCT are to determine the impact of a structured post-treatment surveillance upon the detection and treatment of cancer recurrence and health-related quality of life, including anxiety and to assess the cost-effectiveness. We will undertake a national prospective, multi-centre, randomised controlled trial of structured follow-up including radiological and endoscopic investigations versus standard clinical follow-up. The setting will be at least 24 large oesophago-gastric cancer UK cancer centres. We will aim to recruit 952 oesophageal and gastric cancer patients receiving surgical resection for curatively intended treatment of oesophageal or gastric cancer +/-neoadjuvant/adjuvant chemo(radio or immuno)therapy. At 4-12 weeks after surgery for oesophageal or gastric cancer, patients will be assessed for eligibility for inclusion in the trial. Patients will be randomised 1:1 to receive either intensive follow-up for up to 3-years, with clinical and computerised tomography (CT) investigation every 6 months, and an endoscopy at 12 months or to current standard NHS follow-up, i.e. clinical review at 6 and 12 months followed by targeted investigation as required based upon the onset of new symptoms. The primary outcome is 3-year all-cause mortality and secondary outcomes include health-related quality of life (including anxiety), 3-year diseasespecific mortality, pattern and treatment of tumour recurrence, and cost-effectiveness of follow-up in both study arms. The findings of this RCT will inform national and international guidelines for patients with oesophageal and gastric cancer, as this will be the first RCT to provide robust evidence concerning the value of surveillance in this population. Clinical trial information: 14417629. Research Sponsor: National Institute for Health Research -Health Technology Assessment.

TPS417 Trials in Progress Poster Session

A randomized controlled phase III study comparing surgery alone versus adjuvant nivolumab versus adjuvant S-1 for locally advanced esophageal cancer with no pathological complete response: JCOG2206 (SUNRISE Trial).

First Author: Satoru Matsuda, Department of Surgery, Keio University School of Medicine, Tokyo, Japan

Background: On the basis of JCOG1109, neoadjuvant chemotherapy (NAC) with Docetaxel, Cisplatin, and 5-FU (DCF) has become one of the standard treatments for locally advanced esophageal squamous cell carcinoma (LAESCC). Although the efficacy of adjuvant therapy with nivolumab after preoperative chemoradiotherapy for LAESCC has been proven by CheckMate 577, the survival benefits of adjuvant therapy after NAC remain controversial.

Additionally, a single-arm phase II trial of adjuvant S-1 for LAESCC who received NAC demonstrated favorable survival outcomes and safety. Methods: Eligibility criteria include the followings: thoracic esophageal squamous cell carcinoma, adenosquamous carcinoma, or basaloid squamous cell carcinoma, reception of NAC (at most three courses of DCF or two courses of Cisplatin plus 5-FU) and a diagnosis of clinical stage I (except for T1N0), II, III, IVA (except for T4), or IVB (only supraclavicular lymph node metastasis except for T4), right thoracoabdominal esophagectomy with D2 or higher lymph node dissection, R0 resection was performed, residual pathological disease in the resected specimens [ypStage T0-4aN1-3M0, T1-4aN0M0, T0-4aNanyM1 (only supraclavicular lymph node metastasis)] , aged 18-80 years, ECOG performance status 0 or 1, and adequate organ function. The primary endpoint is relapse-free survival (RFS), and the secondary endpoints are disease-free survival, overall survival, adverse events, and incremental cost-effectiveness ratio. After the confirmation of patient eligibility including pathological diagnosis, patients will be randomized (1:1:1) to either the observation alone arm, adjuvant nivolumab arm (240 mg/body every two weeks or 480 mg/ bodies every four weeks for one year), or adjuvant S-1 arm (four courses of twice-daily oral S-1 for four weeks followed by two weeks of rest for 6 month, three dose levels of S-1 are set according to the patient's body surface area (BSA), as follows: BSA , 1.25 m 2 , 40 mg; BSA 1.25-1.50 m 2 , 50 mg; BSA . 1.50 m 2 , 60 mg, twice a day). We assumed a three-year RFS of 60% in the observation alone arm and expected an 11% increase for the nivolumab arm and the S-1 arm (HR = 0.67). The total required sample size was calculated as 435 (145 per arm) to achieve the desired power of 70% for each pair comparison (observation alone arm vs. the nivolumab arm and observation alone arm vs. S-1 arm) with an overall one-sided alpha of 5%, an accrual period of 5.5 years, and a follow-up period of three years. The planned sample size was set at 450 patients (150 patients per arm). This trial has been registered in the Japan Registry of Clinical Trials as jRCTs031230219. This trial was initiated in July 2023, and the first patient was enrolled in September 2023. Clinical trial information: jRCTs031230219. Research Sponsor: None.

TPS418 Trials in Progress Poster Session

Randomized phase II study comparing neoadjuvant FLOT versus DOS for patients with type 4 or large type 3 gastric cancer (JCOG2204). First Author: Izuma Nakayama, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Koto-Ku, Japan Background: A randomized phase III trial (JCOG0501) failed to demonstrate a survival advantage of neoadjuvant chemotherapy with S-1 plus cisplatin (SP) for patients with resectable macroscopic type 4 and large type 3 gastric cancer (GC). Currently, initial resection followed by adjuvant chemotherapy is performed as the standard treatment for this population as well as general type GC in Japan. However, macroscopic type 4 and large type 3, mostly overlapping with scirrhous or linitis plastica type, have distinctive natures in age, dominant histology and metastatic site, exhibiting unfavorable prognosis after surgery with curative intent. Further therapeutic development using peri-operative chemotherapy is urgently desired for the improvement of this hard-to-treat subset of GC. Based on the successful results of the FLOT4 trial and PRODIGY trial, FLOT (5-fluorouracil/leucovorin/ oxaliplatin/docetaxel) and DOS (docetaxel/oxaliplatin/S-1) will be anticipated to offer more potent efficacy compared to platinum doublet. However, it remains unclear which of these two regimens should be selected as a test arm of future phase III confirming efficacy of neoadjuvant chemotherapy in Japan. Methods: JCOG2204 is a multi-center, randomized phase II trial comparing neoadjuvant chemotherapy with FLOT (5-fluorouracil/levofolinate/ oxaliplatin/docetaxel) versus DOS for resectable type 4 and large type 3 GC. This trial adopted the selection design to determine the most promising regimen for the subsequent phase III trial. Patients with histologically confirmed adenocarcinoma of the stomach, presenting with macroscopic type 4 or larger lesions ($8 cm) of type 3, are eligible for this trial. Prior to registration, it is required to confirm the absence of non-curable factors other than positive lavage cytology (CY1) or peritoneal dissemination localized around the stomach (P1a) in a staging laparoscopy. Neoadjuvant FLOT arm consist of 4 courses of oxaliplatin (85 mg/m 2 ) and docetaxel (50 mg/m²) with levofolinate (200 mg/m 2 ) IV infusion for 1-2 hours, then 5-FU (2600 mg/m 2 , civ) for 24 hours on day 1, biweekly. Neoadjuvant DOS arm consists of 3 courses of oxaliplatin (100 mg/m 2 ) and docetaxel (40 mg/m 2 ) IV infusion for 1-2 hours on day 1, followed by oral S-1 80-120 mg/m 2 /day for 2 weeks (days 1-14), in a 3-week cycle. Adjuvant chemotherapy is performed according to the pathological TNM stage. A sample size was calculated based on Simon's selection design assuming that a proportion of patients achieving pathological response Grade 1b or higher will be 65% in the superior regimen, 10% higher than 55% in the other. A total of 76 patients, which are required to ensure at least an 80% probability of correct selection, are planned to be enrolled over 2 years. Enrollment in JCOG2204 begun on 14 th July, 2023 and clinical trial information is available in Japan Registry of Clinical Trials (jRCTs031230231). Clinical trial information: jRCTs031230231. Research Sponsor: None.

First-in-human phase 1/2 trial evaluating TAC01-CLDN18.2 autologous T cells in CLDN18.2-positive solid tumors. First Author: Ecaterina Elena Dumbrava, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX Background: CLDN18.2 is a tight junction protein expressed in differentiated gastric epithelial cells and is abnormally expressed in various solid tumor types, serving as a promising target for therapy. To date, there are no approved therapies directed against this target, but compelling data exist using monoclonal antibodies and conventional CAR T therapy. The T Cell Antigen Coupler (TAC) technology is an approach to modifying T cells ex vivo, which allows recognition and cytotoxicity of tumor cells by co-opting the natural T cell receptor. The TAC technology has a safer profile than conventional CAR T therapies and is used to create an autologous TAC01-CLDN18.2 T cell product targeting CLDN18.2. Methods: This first in-human trial (NCT05862324) is designed to assess both the safety profile and preliminary antitumor activity of TAC01-CLDN18.2 in patients with CLDN18.2+/HER2-solid tumors after $ 2 lines of therapy. The phase 1 dose escalation segment employs a traditional 3+3 dose-escalation design to evaluate increasing doses of TAC01-CLDN18.2 with estimated enrollment numbers of 9 to 24 subjects. The subsequent phase 2 will further evaluate the efficacy, safety, and pharmacokinetics of the optimal TAC01-CLDN18.2 dose. With 3 cohorts, Group A will enroll up to 57 subjects with gastric and esophageal adenocarcinoma, Group B aims to enroll 10 subjects with pancreatic ductal adenocarcinoma (PDAC) while Group C will examine up to 22 subjects with ovarian and non-small cell lung cancer (NSCLC). Groups A and C will leverage a Simon 2-stage design to assess whether the treatment achieves efficacy, while Group B will be exploratory with an opportunity for cohort enrichment based on clinical data. Prior to TAC01-CLDN18.2 infusion, subjects will undergo leukapheresis and may receive bridging anticancer therapy as appropriate during cell manufacturing. CLDN18.2 expression levels will be determined centrally using a clinical trial assay validated across relevant indications. Subjects will then undergo low intensity lymphodepletion chemotherapy. A second dose of TAC01-CLDN18.2 may be administered based on prespecified safety and clinical criteria. Evaluation of DLTs will take place within a 28-day window following the first infusion. In both phases, CLDN18.2+/ HER2-solid tumor patients must have completed at least two prior therapy lines except for PDAC patients who may qualify after one prior antineoplastic regimen. For phase 2, up to four prior treatment lines is permissible and definitions of eligible CLDN18.2 expression levels will be based on retrospective analysis of data from Phase 1 in association with clinical efficacy. The trial is currently in the open-enrollment stage, awaiting the inclusion of the inaugural patient. No data analysis is available as of the submission deadline. Clinical trial information: NCT05862324. Research Sponsor: None.

TPS420 Trials in Progress Poster Session

A randomized, multicenter, open-label, phase 2 study of TRK-950 in combination with ramucirumab and paclitaxel as second-line therapy in patients with CAPRIN-1 positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. First Author: Ronan Joseph Kelly, Charles A. Sammons Cancer Center, Baylor University Medical Center at Dallas, Dallas, TX Background: CAPRIN-1 is strongly expressed on the cell membrane of many cancer types including G/GEJ and on cancer stem cells. High expression is associated with enhanced in vitro colony-forming activity and in vivo tumorigenicity. TRK-950 is a first in class humanized antibody targeting CAPRIN-1. 1 In the phase I study (NCT02990481), TRK-950 was well tolerated as monotherapy with no DLTs and MTD not reached at doses of 3-30mg/kg IV weekly. Subsequently the Phase 1b demonstrated that TRK-950 was well tolerated with a high potential for synergistic anti-tumor activity when used in combination with standard of care treatment(s) in selected advanced solid tumors (NCT03872947). Specifically, Regimen D which evaluated TRK-950 in combination with Ramucirumab and Paclitaxel in G/GEJ showed a DCR of 100% in all nine patients receiving 10 mg/kg and partial responses were seen in 5/9 (55%) patients. CAPRIN-1 strong expression was observed in 4/9 patients and an ORR of 100% was seen in those patients.

TPS421 Trials in Progress Poster Session

Cohort expansion from the phase 1 JEWEL-101 study investigating the tissue factor-targeting antibody-drug conjugate XB002 in patients with advanced solid tumors: Pancreatic and esophageal cancer cohorts. First Author: Susanna Varkey Ulahannan, University of Okahoma Health Sciences Center, Oklahoma City, OK Background: Patients (pts) with metastatic pancreatic and esophageal cancers have poor prognosis, with 5-year survival rates of 3% and 6%, respectively (SEER 22). Tissue factor (TF), a factor VIIa receptor involved in initiation of the extrinsic coagulation cascade, is overexpressed in these tumors and has been associated with poor outcomes. XB002 is a novel antibody-drug conjugate (ADC) composed of a high-affinity TF-directed human monoclonal antibody conjugated to the linker-payload zovodotin. Zovodotin consists of an auristatin-based payload with a stable protease-cleavable linker; it is designed to have lower off-target payload deconjugation and improved tolerability versus other auristatin-based ADCs. In preclinical studies, XB002 showed encouraging safety and antitumor activity without affecting coagulation. JEWEL-101 (NCT04925284) is a phase 1, dose-escalation and multi-cohort expansion study evaluating XB002 alone and in combination with nivolumab or bevacizumab in pts with advanced solid tumors. Preliminary results from the dose-escalation stage showed XB002 was well tolerated at multiple dose levels, with low-grade ocular toxicity and no bleeding events or treatmentrelated peripheral neuropathy (PN). 1 Presented here is the design of the expansion cohorts for pancreatic and esophageal cancers. Methods: Eligible pts must have an inoperable, locally advanced, metastatic, or recurrent solid tumor. Pts with pancreatic adenocarcinoma will receive XB002 single agent. Pts enrolled with esophageal squamous cell carcinoma (ESCC) will be randomized between 2 cohorts to receive either XB002 single agent or XB002 plus nivolumab. All pts in the pancreatic cancer and ESCC cohorts must have ECOG performance status of 0-1, measurable disease per RECIST v1.1, and have received 1-2 prior lines of systemic anticancer therapy, and radiographically progressed during or after their last therapy.

TPS422 Trials in Progress Poster Session

Surgeon fatigue in robot-assisted and laparoscopic gastrectomy for gastric cancer: Exploratory prospective observational study ancillary to JCOG1907 randomized controlled trial (JCOG1907A1). First Author: Keiichi Fujiya, Division of Gastric Surgery, Shizuoka Cancer Center, Nagaizumi, Japan Background: Fatigue is being increasingly recognized as an important factor in surgical procedures, because it leads to errors in surgeons' decisions and reduced operating efficiency. In comparison to laparoscopic surgery, robot-assisted surgery is expected to reduce surgeon fatigue due to ergonomic adjustments, comfortable sitting positions, minimal restriction of instrument movement, and stable visualization. The aim of this study is to assess surgeon fatigue and explore the superiority of robot-assisted gastrectomy over laparoscopic gastrectomy in surgeon fatigue. Methods: This study is conducted as a prospective observational study ancillary to a randomized controlled phase III trial investigating the superiority in safety of robot-assisted gastrectomy over laparoscopic gastrectomy for clinical stage T1-4aN0-3 gastric cancer (JCOG1907: UMIN000039825). The lead surgeon and the first assistant performing surgeries as protocol treatment in JCOG1907 were included. Surgeon fatigue is quantitatively assessed using multiple assessment tools. The primary endpoint is the average NASA-Task Load Index (NASA-TLX) value for the lead surgeons. Secondary endpoints include six individual parameters of NASA-TLX, visual analog scale assessments for fatigue, advanced trail-making tests, and continuous heart rate variability measurements for lead surgeons and first assistants. The primary analysis compares surgeon fatigue between robot-assisted and laparoscopic surgery. Secondary analyses examine the association between surgeon fatigue and various factors, such as surgeon and patient background, and surgical findings, as well as cross-correlations among measures of surgical fatigue. In addition, the association between surgeon fatigue and postoperative complications and its impact on long-term survival outcomes is also evaluated. The sample size is 500 surgical cases, with a planned accrual period of 2 years. This study was initiated in April 2023 and registered at the University Hospital Medical Information Network as UMIN000052120. As of August 2023, 52 cases (10.4% of the planned accrual) have been enrolled in the study. Clinical trial information: UMIN000052120. Research Sponsor: National Cancer Center Research and Development Fund.

A phase II trial of CapeOX plus nivolumab for early relapsed HER2-negative gastric cancer (JACCRO GC-11: FirSTAR trial). First Author: Hiroyuki Arai, Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan Background: Fluoropyrimidine-based post-operative chemotherapy is one of the standard adjuvant therapies for curatively resected gastric cancer (GC). 1,2 The current standard first-line chemotherapy consists of fluoropyrimidine and oxaliplatin combined with nivolumab in advanced HER2-negative GC patients including cases with a recurrence . 6 months after completion of post-operative chemotherapy, based on the CheckMate 649 and ATTRACTION-4 trials. However, in GC patients with early recurrence during or # 6 months after completion of post-operative 5-FU based chemotherapy, optimal treatments remain to be established. A previous phase II study showed that capecitabine plus cisplatin is an active regimen for early relapsed GC after postoperative S-1 monotherapy.

TPS425 Trials in Progress Poster Session

348 Poster Session

Safety and efficacy of nanosomal docetaxel lipid suspension (NDLS) in patients with advanced gastric adenocarcinoma. First Author: Vikas S. Ostwal, Tata Memorial Hospital (HBNI), Mumbai, India

Background: Nanosomal docetaxel lipid suspension (NDLS) was developed to overcome toxicity issues associated with conventional docetaxel. Docetaxel, cisplatin, 5-fluorouracil (5-FU; DCF) or modified DCF (mDCF) is one of the recommended first-line regimens for patients with metastatic gastric adenocarcinoma (GAC). However, majority of the patients experienced grade 3/4 toxicities with DCF regimen using conventional docetaxel. The present study evaluated the safety and efficacy of NDLS-based mDCF/DCF regimens in patients with metastatic GAC. Methods: In this multicentric, open-label, clinical trial, patients with previously untreated metastatic GAC were enrolled. Patients received either mDCF [NDLS 40 mg/m 2 on day 1 (D1), C 40 mg/m 2 on D2 or D3, 5-FU 400 mg/m 2 bolus on D1, leucovorin 400 mg/m 2 on D1, 5-FU 1000 mg/m 2 /day continuous infusion D1 & 2; q2w] for 9 cycles, or DCF [NDLS 75 mg/m 2 on D1, C 75 mg/m 2 on D1, 5-FU 750 mg/m 2 /day for 5 days given as continuous infusion; q3w] for 6 cycles. Prophylactic GCSF (Granulocyte Colony Stimulating Factor)/ Peg-GCSF support was allowed in all patients. The primary endpoint was overall response rate (ORR) at week 18. Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety outcomes. Patients were followed up to 1 year. Results: Fifty-two patients were enrolled, with mean (6SD) age of 52 (69.6) years & male:female ratio of 32:20. Thirtyeight patients qualified for modified intent-to-treat (mITT) analysis for efficacy evaluation (mDCF: 33; DCF:5). At week 18, ORR was 57.9% & DCR was 81.6% in mITT population. In the per-protocol population (n=26), ORR was 61.5% at 18 weeks (mDCF:63.6%; DCF:50%

350 Poster Session

Evaluation of the efficacy and safety of a 3-weekly TS-1 regimen as adjuvant therapy for stage II and III advanced gastric cancer: A pilot study. First Author: Jihong Bae, Division of Medical Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, South Korea Background: Adjuvant therapy for stage II and III advanced gastric cancer (AGC) is essential in improving patient outcomes. The standard therapy, TS-1 at 80 mg/m 2 /day for 4 weeks with a 2-week rest, is recommended for 1 year or 8 courses. This study investigates the efficacy and safety of a 3-weekly adjuvant TS-1 regimen in AGC patients. Methods: We conducted an analysis of 93 patients who underwent gastrectomy with D2 lymphadenectomy and initiated a 3-weekly adjuvant TS-1 regimen between February 2017 and May 2022. The novel regimen consisted of TS-1 at 80 mg/m2/day for 2 weeks, followed by a 1-week rest, with a treatment goal of 1 year or 16 courses.

Results: Among the 93 patients, 12 (13%) experienced disease recurrence during a median follow-up of 24.6 months (range: 4.2 to 63.3 months). Of the Stage II patients (n=73), 7 cases (9.5%) had recurrent disease, while 5 cases (25%) in the Stage III group (n=20) experienced recurrence. Recurrence-Free Survival (RFS) rates at 1 year, 3 years, and 5 years were 92.0% (95%CI 86.5 to 97.9), 84.7% (95%CI,76.4% to 93.9%), and 78.6% (95%CI, 65.8% to 94.0%), respectively. A total of 80 patients (86%) completed the adjuvant 3-weekly TS-1 treatment for 1 year or 16 courses, while 25 patients (26.9%) completed the treatment with dose reductions. Adverse events, primarily Grade 1 or 2 diarrhea (28%) and nausea (20%), were manageable. Conclusions: The novel 3-weekly TS-1 regimen as adjuvant therapy exhibited favorable efficacy and tolerable toxicity in AGC patients. These findings suggest the need for further investigation of this regimen in future clinical studies. Research Sponsor: None.

351 Poster Session

Camrelizumab plus apatinib and SOX as first-line treatment in patients with alpha-fetoprotein-producing gastric or gastroesophageal junction adenocarcinoma: A single-arm, multi-center, phase 2 trial. Background: Neoadjuvant chemoradiation therapy followed by radical surgery has been extensively recommended for locally advanced esophageal squamous cell carcinoma (ESCC). However, toxicities and challenges to the subsequent surgery limit its wide clinical application. Immune checkpoint inhibitors combined with antiangiogenesis have synergistic effects and have shown good therapeutic effects in previous studies, as well as fewer side effects. Here, we tested a novel combination of anlotinib (an antiangiogenic kinase inhibitor) and penpulimab (an anti-PD-1 antibody), without the use of radio-or chemotherapy, for the neoadjuvant therapy of locally advanced ESCC. Methods: In this prospective, single-arm, phase II clinical trial (ChiCTR2200064848), patients(pts) with resectable locally advanced ESCC (clinical stage III-IVa) were recruited. The study was designed using a two-stage minimax approach. The estimated sample size was 40 pts would provide 80% power at a onesided alpha error of 5%, threshold pathological complete response (pCR) of 16% and expected pCR of 30%. Here, the first-stage data was included. Notably, 85% (22/25) enrolled pts had medical contraindications (including cardiopulmonary diseases or other underlying medical conditions, along with poor nutritional status and so on). Pts received neoadjuvant therapy with anlotinib (8 mg, po, D1-14, Q3W) combined with penpulimab (200 mg, ivgtt, Q3W) for 2 cycles. Six to eight weeks later, pts underwent radical surgery after exclusion of contraindications. No satri-cel treatment-related death occurred. For all patients, the best ORR was 26.3%, the median DOR was 3.7 months and the CBR was 42.1%. The median PFS was 5.2 months, and overall survival was 12.8 months (95% CI 5.7-NE) after leukapheresis, and the median PFS was 3.3 months, and overall survival was 8.9 months (95% CI 3.3-NE) after the first infusion. In the GC/GEJ group, the ORR was 42.9% (3/7), the median DOR was 6.9 months and the CBR was 57.1%. In the PC group, the ORR was 16.7% (2/12), the median DOR was 3.4 months and the CBR was 33.3%. An ORR of 42.9% (3/7) and a CBR of 71.4% were reported at the DL3 of 600310 6 cells which was selected as RP2D. At DL3, one GC patient achieved a CR and two PC patients had PR, suggesting the PC group achieved an ORR of 40% (2/5) and the GC group achieved an ORR of 50% (1/2 Background: Peritoneal relapse is seen in 60-70% of patients with diffuse type gastric cancer (gc), compared to 20-30% with intestinal type according to Laurens`s classification. Hyperthermic intraperitoneal chemoperfusion (HIPEC) is an increasingly used therapy method for patients (pts) with peritoneal metastases. The preventive use of HIPEC could represent an approach for diffuse type cell gc pts before macroscopic peritoneal seeding has evolved, since pts with operable disease are fit and may have potential risk of microscopic involvement, thus having a theoretical chance of cure with HIPEC even without the need for cytoreduction. Methods: This is a multicenter, randomized, controlled, open-label phase III study including a total of 200 pts with localized and locally advanced diffuse type cell adenocarcinoma of the stomach and type II/III gastroesophageal junction (i.e. $cT3 any N or any T N positive). A negative diagnostic laparoscopy before treatment and 3-6 pre-operative cycles of FLOT are a prerequisite for enrollment (Docetaxel 50 mg/m 2 ; Oxaliplatin 85 mg/m 2 ; Leucovorin 200 mg/ m 2 ; 5-FU 2600 mg/m 2 , q2wk). Pts were randomized 1:1 to receive surgery only and postoperative FLOT (Arm A-control arm) or surgery + intraoperative HIPEC (cisplatin 75mg/m 2 solution at 42°C for 90 min) and postoperative FLOT (Arm B-experimental arm). Surgery is carried out as subtotal, total gastrectomy or transhiatal extended gastrectomy. The scope of the trial is to evaluate the efficacy as well as the safety and tolerability of the combination of perioperative chemotherapy combined with an intraoperative prophylactic HIPEC. Here, we show safety results from the pre-specified safety analysis after 20 pts had undergone surgical resection plus HIPEC and the corresponding 20 pts in the control arm. Results:

360 Poster Session

Phase I trial of intraperitoneal paclitaxel in patients with gastric adenocarcinoma and peritoneal carcinomatosis or positive peritoneal cytology. First Author: Brian D. Badgwell, The University of Texas MD Anderson Cancer Center, Houston, TX

Background: The purpose of this Phase I trial was to evaluate the safety and toxicity of repeated normothermic intraperitoneal paclitaxel for patients with gastric cancer metastatic to the peritoneum. Methods: In patients with gastric adenocarcinoma and peritoneal carcinomatosis or positive peritoneal cytology, a Bayesian optimal interval design was used to prospectively identify the safety and tolerability of escalating doses of intraperitoneal paclitaxel administered as 3 weekly treatments followed by a 1-week break and then 3 additional weekly treatments. The primary objective was to define the maximum tolerated dose (MTD). Secondary objectives included determining the safety and tolerability of escalating doses of intraperitoneal paclitaxel and making a preliminary assessment of the antitumor activity based on the peritoneal carcinomatosis index (PCI) and overall survival (OS).

Results: A total of 25 patients were treated between January 2020 and April 2023. The MTD for intraperitoneal paclitaxel was 100 mg/m 2 . Five patients (20%) had dose-limiting toxic effects at 100 mg/m 2 . Treatment-related grade 3-4 toxic effects included leukopenia in 8 patients (32%) and neutropenia in 8 (32%). Seven patients (28%) required a schedule change to every-other-week treatment. The PCI after intraperitoneal paclitaxel demonstrated progression in 5 patients (20%), stable disease in 5 (20%), and improvement in 10 (40%); 5 patients (20%) were not evaluable for PCI. Eight patients (32%) had resolution of their peritoneal disease, and 7 (28%) underwent attempted resection. The median OS from the time of diagnosis of metastatic disease was 17.9 months (95% CI 14.5-29.5) and from the date of treatment initiation was 10.3 months (95% CI 6.5-18.8). One-, 2-, and 3-year OS rates from the time of diagnosis of metastatic disease were 84%, 36%, and 22%, respectively. Pharmacokinetic analysis showed there was systemic absorption of paclitaxel and plasma AUC 0-' and C max was (13955 6 6683 h.ng/ml) and (390 6 191 ng/ml) respectively, while intraperitoneal concentration at the end of infusion was 232 6 65 mg/ml. Conclusions: Paclitaxel may be safely administered at an intraperitoneal dose of 100 mg/m 2 . Neutropenia was common with weekly treatments, and we would recommend every-other-week treatment for future studies. Rates of resolution of peritoneal disease with multimodality therapy were promising, supporting future trials of this strategy and molecular profiling to identify factors associated with treatment response. Phase I trial of short-course chemoradiotherapy followed by chemotherapy as total neoadjuvant therapy for patients with potentially resectable gastric cancer. First Author: Brian D. Badgwell, The University of Texas MD Anderson Cancer Center, Houston, TX Background: The purpose of this phase I trial was to evaluate the safety and toxicity of preoperative short-course chemoradiotherapy (CXRT) in patients with potentially resectable gastric or gastroesophageal adenocarcinoma as part of a total neoadjuvant therapy (TNT) approach. Methods: Patients with potentially resectable gastric or gastroesophageal adenocarcinoma received CXRT consisting of 30 Gy in 10 fractions with concurrent capecitabine or fluorouracil, followed by systemic therapy for 2 months and then surgery. The primary objective was safety of CXRT with secondary endpoints of pathologic complete response, perioperative complications, and overall survival (OS).

Results: A total of 24 patients were treated between March 2021 and December 2022.

Ten patients (42%) presented with bleeding and 3 (13%) presented with gastric outlet obstruction. Two patients (8%) had cirrhosis. Clinical nodal involvement was reported in 12 patients (50%). Twenty patients (83%) had poorly differentiated tumors, and 13 (54%) had signet ring cell histology. All patients completed CXRT. CXRT treatment-related toxic effects included grade 3 lymphopenia in 7 patients (29%), grade 4 lymphopenia in 1 (4%), and grade 3 anemia in 1 (4%). After CXRT, 22 patients (92%) completed 2 months of chemotherapy, 1 patient (4%) with a microsatellite-high tumor completed immunotherapy, and 1 patient (4%) underwent resection without systemic therapy. All patients underwent attempted resection, and gastrectomy was performed in 20 (83%). R0 resection rate was 95%. Pathologic complete response was observed in 2 patients (8%), and # 1% viability was observed in an additional 4 (17%

364 Poster Session

Camrelizumab plus apatinib after progression on immune checkpoint inhibitors in patients with advanced esophageal squamous cell carcinoma (CAP 02 Re-challenge): A single-arm multicenter, phase II trial. First Author: Xiangrui Meng, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China Background: The optimal therapies for patients with advanced esophageal squamous cell carcinoma (ESCC) who have progressed after immune checkpoint inhibitors (ICIs) are unclear. This phase II single-arm study aimed to assess the efficacy and safety of rechallenge with camrelizumab plus apatinib in this population. Methods: This study enrolled patients with unresectable locally advanced, locally recurrent, or metastatic ESCC who had experienced prior progression on ICI treatment. Enrolled patients received camrelizumab 200 mg intravenously every two weeks along with daily oral apatinib 250 mg. Treatment continued until disease progression, unacceptable toxicity, or patient withdrawal of consent. The primary endpoint was the confirmed objective response rate (ORR). Secondary endpoints included disease control rate (DCR), duration of response (DOR), time to response (TOR), progression-free survival (PFS), overall survival (OS), 3and 6-month PFS rates, 6-, 9-and 12-month OS rates, and safety. Results: From September 1, 2021, to March 29, 2023, 49 eligible patients were enrolled and given treatment. Among 38 treated patients who had at least one post-baseline efficacy measurement, the ORR and confirmed ORR were 36.8% (95% CI 21.8-54.0) and 13.2% (95% CI 4.4-28.1); the DCR was 89.5% (95% CI 75.2-97.1); the median DOR was 3.0 months; and the median TOR was 2.2 months. Among the 49 treated patients, the median PFS was 4.6 months (95% CI 3.8-6.5) and OS was 7.5 months (95% CI 5.5-13.6).

Patients who were both PD-L1 positive and had responded to previous ICI therapy had the longest median PFS (5.7 months, 95% CI 3.9-not reached) and OS (9.6 months, 95% CI 7.5-not reached). Grade $ 3 treatment-related adverse events occurred in 34.7% of patients (17/49). Conclusions: This study showed promising efficacy and an acceptable safety profile of camrelizumab plus apatinib for patients with advanced ESCC who had progressed after ICI therapy. The subset of patients who were both PD-L1 positive and had a prior ICI response seemed to benefit most. Clinical trial information: NCT03736863. Research Sponsor: Jiangsu Hengrui Pharmaceuticals Co., Ltd.

365 Poster Session

Safety and efficacy of neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (Neo DCF) therapy for locally advanced esophageal cancer: Real world data analysis. First Author: Mikako Tamba, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan Background: Neoadjuvant chemotherapy with docetaxel, cisplatin plus 5-FU (Neo DCF) is one of the standard treatments for locally advanced esophageal squamous cell carcinoma (ESCC) in Japan based on the results of the JCOG1109 NExT study. As Neo DCF is both highly effective and high rate of adverse events, it is important to confirm clinical outcomes in the clinical practice and to explore clinical factors that predict treatment efficacy and adverse events (AEs) for treatment optimization.

367 Poster Session

A multi-centre review of the efficacy of re-challenge with platinum doublet in patients with oesophagogastric cancer treated with first-line trastuzumab and chemotherapy. First Author: Jamie Weaver, Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom Background: HER2 amplification or overexpression is seen in 15-20% of metastatic oesophagogastric cancers. The ToGA trial showed an OS benefit for the use trastuzumab with platinum and fluoropyrimidine combination therapy (T-FP) in the first line setting. Second line trials of targeted agents have been disappointing with poor response rates and the current standard of care is paclitaxel and ramucirumab in combination. A recent phase 2 trial showed no OS benefit to continuing trastuzumab with second line chemotherapy but data regarding the efficacy of treatment beyond progression with reintroduction of first line chemotherapy (platinum and fluoropyrimidine) is limited and conflicting. Methods: We conducted a multi-centre retrospective review of patients treated with T-FP in the first-line setting between October 2014 and October 2022 at two large tertiary referral oncology centres in the United Kingdom. Baseline demographic factors and clinical data were collected and compared between responders and nonresponders to re-challenge. PFS and OS were estimated using the Kaplan-Meier method.

Results: Data was collected for 225 patients in total treated with first-line trastuzumab.

We identified 20 patients who had received a re-challenge with FP-T. Best response to first-line treatment was partial response (PR) for 19/20 patients with 1/20 patients with stable disease (SD). There were no differences between baseline demographic factors or tumour pathological features between patients receiving a re-challenge and those treated with chemotherapy alone. The median platinum free interval was 17.8 months.

For the re-challenge disease control rate was 75% with an overall response rate of 35% (7 PR, 0 CR). The median number of subsequent trastuzumab cycles was 7, with a median PFS of 6.1 months and median OS of 10 month. Multivariate Cox-regression analysis identified no factors predictive of response in the re-challenge setting. Conclusions: Rechallenge with trastuzumab plus FP chemotherapy is a possible option for patients with relapse. Larger studies will be required to identify predictive biomarkers to identify those patients most likely to benefit. The role of re-assessment of HER2 status at relapse in those receiving re-challenges requires prospective analysis. Research Sponsor: None.

368 Poster Session

Phase II study of GEN-001 in combination with avelumab in patients with PD-L1-positive locally advanced, or metastatic gastric cancer (GC) or gastroesophageal junction cancer (GEJC) who have progressed after second-line (2L) and beyond (GEN001-201 study). First Author: Jeeyun Lee, Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea Background: The relationship between gut microbiota and the response to immune checkpoint inhibitors is likely due to cross-reactivity between microbial and tumor antigens, enhancing dendritic cell (DC) activation, antigen presentation, and inflammatory cytokine production. GEN-001 is a live biotherapeutic product (LBP) consisting of a lyophilized formulation of a strain of Lactococcus lactis. This study is designed to investigate the safety and efficacy of GEN-001 in combination with avelumab (the PD-L1 inhibitor) for patients with PD-L1 positive advanced GC/GEJC. Methods: This is an open-label, single arm, phase II clinical trial for PD-L1 positive (CPS $1) patients with unresectable, locally advanced, or metastatic GC/GEJC who have progressed after second-line and beyond. All patients were treated with GEN-001 (9x10 11 CFU, administered as oral once daily) in combination with avelumab (800 mg, administered as an intravenous infusion every two weeks) until progressive disease, unacceptable toxicity, death, or withdrawal. Tumor response was assessed every 8 weeks for 6 months and every 12 weeks thereafter. The primary endpoint was objective response (OR); secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. Results: As of August 31, 2023, a total of 42 patients were enrolled. 37 patients have been assessed for response. The confirmed partial response (PR) and unconfirmed PR were achieved by 5 patients and 1 patient respectively, 8 patients have experienced as stable disease (SD). Median PFS and median OS were 1.73 months (95% confidence interval [CI]: 1.67-2.37 months) and 7.9 months (95% [CI]: 6.07-NE months). Treatmentrelated adverse events (TRAEs) of any grade occurred in 12 patients (28.6%) and Grade $3 TRAEs occurred in 2 patients (4.8%) out of 42 patients.

Conclusions: Treatment of patients with GC/GEJC with GEN-001 in combination with avelumab in the $ 3L setting showed promising antitumor activities with an overall manageable safety profile. The results from this trial will be updated about its effects on clinical outcome, including survival, safety, and biomarker findings. Clinical trial information: NCT05419362. Research Sponsor: None.

369 Poster Session

Short-term outcomes of pedicled jejunum reconstruction after esophagectomy for esophageal cancer. First Author: Mamoru Matano, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan Background: The number of patients with esophageal cancer after gastrectomy and patients accompanied with simultaneous gastric cancer has gradually increased because of the prevalence of gastric in Japan. Pedicled jejunum is one of the choices for esophageal reconstruction when the stomach is not available. However, surgical outcomes of jejunal reconstruction and the effect of the timing of gastrectomy remain to be elucidated. Methods: This study was a retrospective, cohort study that included 24 patients who underwent supercharged pedicled jejunal conduit for esophageal reconstruction in our institution between May 2007 and July 2023. The patients were divided into two groups: gastrectomy was performed before esophagectomy (A group) and gastrectomy was performed simultaneously for accompanied gastric cancer (S group). Surgical outcomes and postoperative complications were compared between the two groups. As a nutritional assessment, perioperative change in body composition such as visceral fat area (VFA) with computed tomography was analyzed. Results: In 24 patients, the median operative time was 769 minutes and the median blood loss was 543 g. Severe postoperative complications developed in 6 cases (25%). The A group included 15 cases and the S group did 9 cases. There was no statistical difference in postoperative complication between the two groups, however, postoperative hospital stay was statistically longer in the S group than in that of the A group (37 days vs. 21 days, p=0.02). Although weight loss at 1 year after operation was almost identical in the two groups, the loss of VFA was more severe in the S group than in the A group (23 % of preoperative VFA vs. 77% of preoperative VFA, p=0.03). Conclusions: The use of a pedicled jejunal conduit after esophagectomy could be performed safely. Methods: This open clinical study planned to enroll 62 pts with locally recurrent esophageal cancer following radical treatment who aged 18-75 years with ECOG performance status of 0-1. Pts received the following treatments: camrelizumab (200 mg q2w, continuous medication until disease progression, intolerable toxicity, or withdrawal); simultaneous radiotherapy (the total radiation dose was 50-50.4 Gy, which was given by 25-28 fractions, 5 fractions per week, with 1.8-2 Gy for each fraction); chemotherapy (capecitabine, 625mg/m2, bid, oral, d1-5, qw, total 5 weeks). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety.

Results: Between Feb 2022 and Jul 2023, 14 pts with a median age of 71 years old had been enrolled. Among the evaluable pts, the ORR was 69.2% (9/13), the DCR was 100.0% (13/13). With a median follow-up of 16.0 months (95% CI 13.5-18.5), the median PFS was 7.6 months (95% CI 4.2-11.0), the median OS was 18.6 months (95% CI NE-37.6) in the full analysis set. The incidence of any grade adverse events (AEs) was 100.0% and that of grade $3 AEs was 57.1% of 14 pts.

372 Poster Session

Management of nausea and vomiting (N/V) following first-line (1L) zolbetuximab + chemotherapy treatment in claudin-18.2 (CLDN18.2)+, HER22, locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: Analysis from the phase 3 SPOT-LIGHT and GLOW studies. First Author: Kohei Shitara, Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan

Background: The phase 3 SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) studies showed clinically meaningful, statistically significant improvement in PFS and OS using 1L zolbetuximab + chemotherapy vs placebo (PBO) + chemotherapy in patients (pts) with CLDN18.2+, HER22, LA unresectable or mG/GEJ adenocarcinoma. N/V were the most common treatment-emergent adverse events (TEAEs) reported in the zolbetuximab arm of these studies. We report an analysis of the incidence and management of N/V in SPOTLIGHT and GLOW. Methods: In SPOTLIGHT, pts (N = 565) were randomized 1:1 to zolbetuximab + mFOLFOX6 vs PBO + mFOLFOX6. In GLOW, pts (N = 507) were randomized 1:1 to zolbetuximab + CAPOX vs PBO + CAPOX. In both studies, neurokinin-1 receptor blockers (NK-1), selective serotonin receptor blockers (5-HT3), and other prophylactic antiemetic regimens were recommended to prevent and mitigate N/V per institutional care and guidelines. Results: A total of 279 pts in SPOTLIGHT and 253 pts in GLOW received zolbetuximab + chemotherapy. In SPOTLIGHT and GLOW combined, nausea occurred in 58% vs 18% of pts, and vomiting occurred in 43% vs 15% of pts in the first vs second zolbetuximab infusions, respectively; lower incidences of N/V were observed thereafter. During the first zolbetuximab infusion, the first episode of N/V occurred within 1 hour (median time, 48.0 min in SPOTLIGHT and 56.5 min in GLOW). Antiemetic usage and associated N/V rates are presented in the Table . The 96 pts in SPOTLIGHT and 52 pts in GLOW who had infusion modifications in cycle 1 due to TEAEs had numerically higher infusion rates than pts without infusion modifications; 85% of these modifications in SPOTLIGHT and 79% in GLOW were due to N/V. Zolbetuximab was discontinued within the first 9 weeks in 11 and 7 pts in SPOTLIGHT and 6 and 4 pts in GLOW due to nausea or vomiting, respectively. Conclusions: In SPOTLIGHT and GLOW, slower infusion rate and use of antiemetic combinations may have helped to mitigate N/V. These strategies will be important to support continued treatment and allow pts to achieve maximum clinical benefit with zolbetuximab + chemotherapy. Clinical trial information: NCT03504397 and NCT03653507. Research Sponsor: Astellas Pharma Inc.

All-grade N/V with antiemetic usage at C1D1.

5-HT3 Only

376 Poster Session

The implication of failure patterns after neoadjuvant chemoradiotherapy with small involved-field in esophageal squamous cell carcinoma. First Author: Hyunju Shin, Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea Background: In this study, we aimed to analyze failure patterns, the clinical and biological prognostic factors for treatment outcomes, and evaluate the feasibility of involved-field irradiation (IFI) in patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemoradiotherapy (CCRT). Methods: We retrospectively reviewed the medical records of 511 patients diagnosed with ESCC and underwent neoadjuvant CCRT and radical esophagectomy between January 2016 and February 2022 at Samsung Medical Center. For IFI, the clinical target volume (CTV) was defined as the primary gross tumor volume (GTV) plus a 2.0-3.0 cm longitudinal margin and a 0.5-1.0 cm circumferential margin, as well as the GTV of lymph nodes (LN) plus a 0.5-1.0 cm margin. For elective nodal irradiation (ENI), the CTV encompassed supraclavicular, mediastinal, or abdominal LN regions based on the primary tumor location. IFI was applied in most cases (98%). The failure patterns, loco-regional control (LRC), and survival outcome were analyzed. Regional lymph nodes (LNs) were defined and classified according to the AJCC 8th edition. Non-regional LNs were defined as metastatic LNs in neck, thorax, abdominal area except regional LNs.

Results: With a median follow-up of 44.4 months, 213 (41.7%) patients experienced recurrence. The first recurrent sites were locoregional (LR) in 98 patients (19.2%), non-regional LN in 81 (15.9%), and distant organs in 152 (29.7%). Among the 98 patients with LR recurrence, RT in-field failure occurred in 53 (10.4%) patients, in & out-field failure in 18 (3.5%), and out-field failure in 27 (5.3%). In 27 cases of out-field failure only, LR recurrent lesion could be included in the target volume in 7 (1.4%) cases if ENIs were applied. Among the 27 patients, 10 received salvage treatment and 2 did not experience further recurrence. The analysis for the detailed LN recurrence showed that the upper mediastinal and supraclavicular LNs were the most frequent area, regardless of the primary tumor location and other clinical factors. Among 213 recurrent cases, 54 (10.5%) recurred in upper paratracheal LN and 40 (7.8%) in supraclavicular LN. The 5-year LRC rates, disease-control rates, and overall survival (OS) rates were 77.5%, 53%, and 54.3%, respectively. Multivariate analysis revealed that gender, age, cStage, ypStage, and resection margin status were independent prognostic factors for OS. Conclusions: Neoadjuvant CCRT using IFI with a small margin showed favorable treatment outcomes and out-field recurrence that the traditional ENI field could cover accounted for a small portion; thus, it might be feasible in the neoadjuvant setting. However, we need to consider that the upper mediastinal and supraclavicular areas were the most frequent recurrence sites. Research Sponsor: None.

377 Poster Session

PD1 and CD39 expression on tumor infiltrating lymphocytes in patients with gastric cancer. First Author: Takafumi Okayama, National Cancer Center Hospital East, Kashiwa, Japan Background: Activation and clonal expansion of tumor antigen-specific T cells in cancer patients are crucial for immunotherapies. Recent reports indicate that CD39 is a marker to distinguish tumor-reactive CD8 T cell populations from bystander populations. In gastric cancer (GC), anti-CD39 antibody, anti-PD-1 antibody, and FOLFOX combination therapy may be effective therapy at AACR 2022. Methods: We retrospectively reviewed the data of 62 GC patients who underwent gastrectomy at our hospital (2017 -2018) and examined their rejected specimen's immune-microenvironment using immunohistochemistry. Then we prospectively enrolled 16 GC patients. Their tumor tissue and tumorinfiltrating lymphocytes (TILs) were extracted from surgical specimens, these fractions were subjected to the RNA-seq analysis (n = 3), CD107a degranulation assay (n = 7) and 3H-Thymidine incorporation assay (n = 7). Results: The densities of CD39 + CD8 TILs positively correlated with the densities of CD4 T cells and B-cells in GC tissues (P = 0.01, , 0.01, respectively). Furthermore, higher densities of CD39 + CD8 TILs in GC patients were associated with better overall survival (P , 0.01). We classified TILs into four groups based on expression levels of the PD-1 and CD39. The proportion of CD39 + CD8 T cells was significantly higher in GC tissues than their PBMCs (n = 13) and non-cancerous tissues (n = 4). CD39 + PD-1 + CD8 (DP) TILs in primary tumors were elevated expression of multiple inhibitory receptors such as LAG3, TIGIT and reduced expression of IL-2 by RNA-seq analysis. T cells expanded in vitro from DP-TILs (n = 5) efficiently recognized autologous tumor cells in CD107a assay compared with other populations, and considered to be tumor-reactive T cells fraction. However, since these DP TILs in primary tumors show exhausted phenotypes, capacities to kill tumor are expected to be reduced in the tumor-microenvironment (TME). By adding ATP to the DP-TILs in vitro at the concentration reported in the TME, we observed reduction of cell proliferation by 3H-thymidene incorporation assay and of degranulation by CD107a assay, and we observed recovery of these changes by adding anti-CD39 inhibitory antibody. Conclusions: DP-TILs may have superior T cell receptors recognizing tumorantigens and contribute to tumor eradication, especially when administrated anti-CD39 antibody. Research Sponsor: None.

384 Poster Session

Exploratory analysis of biomarkers of response to durvalumab in advanced HER2-negative oesophago-gastric adenocarcinoma within a phase 2 clinical trial. First Author: Hazel Lote, The Institute of Cancer Research and The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom Background: Advanced oesophago-gastric cancers have showcased varied responses to immunotherapy based on biomarkers such as tumour mutational burden, microsatellite instability, and PD-L1 expression. However, these markers may not fully capture tumour heterogeneity and evolutionary dynamics. Hence, understanding the intricate relationship between immune selection, specifically immune dN/dS, 1 and tumour evolution is vital for devising personalized therapeutic strategies. Methods: In our phase 2 open label, multicentre, randomised PLATFORM trial (NCT02678182), patients received maintenance durvalumab post first-line chemotherapy. A survival advantage was not seen with maintenance durvalumab compared to surveillance and exploratory analysis of PD-L1 expression was not associated with improved survival outcomes. 2 However, a subset of patients treated with durvalumab experienced durable responses and some experienced incremental radiological responses. A pilot substudy on a selected cohort (n=24) of these patients was designed to explore the potential of immunogenomics evolutionary-based metrics, notably dN/dS, as predictive biomarkers. DNA and RNA from FFPE baseline tumour samples underwent analysis, examining genomic factors including tumour mutational burden, indel signatures, PDL1 status, and immune evasion mechanisms. Furthermore, the evolutionary metric, immune dN/dS, which has implications in tumour immunoediting and its response to immunotherapies, was scrutinized. Results: A dominant indel mutational signature emerged from the analysis. The majority of patients displayed a significantly higher number of indel variants, compared to non-synonymous and synonymous single-nucleotide variants.

385 Poster Session

The expanded indications of HER2-targeted therapies by monitoring of circulating tumor cells. First Author: Yasuaki Kimura, Saitama Medical Center, Jichi Medical University, Saitama, Japan Background: Despite success in the HER2 targeted therapies for metastatic gastric cancer patients, the conventional assessment of HER2 status in tumor tissue specimens is still under debate. Methods: Twenty-seven patients with metastatic gastric cancer were treated according to histological HER2 status. On-chip sorting system was used for the isolation of circulating tumor cells (CTCs) before treatments. Epithelial mesenchymal transition (EMT) was assessed by the vimentin and cytokeratin. DNA was extracted from CTCs and applied to the gene panel with 409 cancer related genes. The fluorescence signal intensity . 50 is set to be a threshold value for distinguishing between positive and negative HER2 on CTCs. Results: Thirteen patients (48%) with HER2 positive in tumor tissues (Group A) were treated with cytotoxic agents and trastuzumab (anti HER2 antibody) while 14 patients (52%) were negative and treated with cytotoxic agents. In these 14 patients, 8 patients (30%) showed HER2 positive (Group B) and 6 patients (22%) displayed HER2 negative (Group C) on CTCs.

388 Poster Session

The usefulness of ctDNA and exosome DNA as biomarkers in esophageal squamous cell carcinoma. First Author: Tomoki Nakai, Second Department of Surgery, Wakayama Medical University, Wakayama, Japan Background: Recently, the usefulness of exosome DNA (exo-DNA) for prognostic analysis of various solid tumors has also been reported. In this study, we investigated the usefulness of ctDNA and exo-DNA as biomarkers for esophageal squamous cell carcinoma. Methods: Patients with esophageal squamous cell carcinoma undergoing standard treatment had ctDNA and exo-DNA collected over time. NGS analysis was performed on biopsy or surgical specimens, and mutated genes in individual cases were followed by ddPCR over time. Results: NGS analysis was performed on 16 patients. 12 of 16 cases showed mutations, In 8 cases, ctDNA and exo-DNA could be measured by ddPCR over time. In one case of Stage IVA. both ctDNA and exo-DNA were useful to determine the efficacy of chemotherapy and radiotherapy, and in one case of Stage II, both ctDNA and exo-DNA were useful to predict postoperative recurrence.

Conclusions: In esophageal squamous cell carcinoma, ctDNA and exo-DNA may be useful in determining treatment response and predicting recurrence. We will further investigate the usefulness of ctDNA and exo-DNA in esophageal squamous cell carcinoma, including prognostic prediction. Clinical trial information: UMIN000045311. Research Sponsor: None.

389 Poster Session

Microsatellite instability (MSI) in patients with gastric cancer (GC) and correlation with PD-L1 expression.

396 Poster Session

Circulating exosomal microRNA signature to predict peritoneal metastasis in patients with advanced gastric cancer. First Author: Yuma Wada, Tokushima University, Tokushima, Japan Background: Despite of radical operation, about half of gastric cancer (GC) patients with advanced GC develop peritoneal metastasis (PM) and the patients with PM has poor prognosis. However, because staging laparoscopy was high invasive procedure for the patients, identification of PM by using liquid biopsy can be useful in patients with GC. Methods: We analyzed two genome-wide miRNA expression profiling datasets (GSE164174 and TCGA). We prioritized biomarkers in pretreatment plasma specimens from clinical training and validation cohorts of patients with GC. We developed an integrated exosomal miRNA panel and established a risk-stratification model, which was combined with miRNA panel and currently used tumor markers (CEA, CA19-9, CA125, and CA72-4 levels). Results: Our comprehensive discovery effort identified a 4-miRNA panel that robustly predicted the metastasis, with an excellent accuracy in TCGA dataset (AUC=0.86). We successfully established a circulating exosomal miRNA panel with remarkable diagnostic accuracy in the clinical training (AUC=0.85) and validation (AUC=0.86) cohorts. Moreover, the predictive accuracy of the panel was significantly superior to conventional clinical factors (P,0.01), and the risk-stratification model was dramatically superior to the panel and currently used clinical factors for predicting PM (AUC=0.94, univariate: OR = 77.00, P , 0.01; multivariate: OR = 57.71, P = 0.01). Conclusions: Our novel risk-stratification model for predicting PM has a potential for clinical translation as a liquid biopsy assay in patients with GC. Our findings highlight the potential clinical impact of our model for improved selection and management of patients with this malignancy. Research Sponsor: None.

Phase 2 study of pembrolizumab plus lenvatinib and belzutifan in patients with metastatic esophageal squamous cell carcinoma. First Author: Carlos Rojas, Centro de Investigacion Clinica, Bradford Hill, Santiago, Chile Background: Initial signal finding studies demonstrated promising antitumor activity with the anti-PD-1 antibody pembrolizumab in combination with the anti-angiogenic multikinase inhibitor lenvatinib in patients with advanced gastric cancer or head and neck squamous cell carcinoma. Because hypoxia is common in many solid tumors and is known to induce an immunosuppressive tumor microenvironment, targeting hypoxia-inducible factor-2 alpha (HIF-2a) may enhance the activity of immune checkpoint inhibitors. The ongoing phase 2 LITESPARK-016 study (NCT04976634) is evaluating the combination of pembrolizumab plus lenvatinib and the HIF-2a inhibitor belzutifan (MK-6482) in multiple solid tumors. LITESPARK-016 includes 2 esophageal squamous cell carcinoma cohorts: one enrolling patients with immunotherapy-naive and the other enrolling patients with immunotherapyresistant esophageal squamous cell carcinoma, cohorts F and G, respectively. We report the methodology for these cohorts. Methods: In this phase 2, open-label, multicenter study, eligible patients in the esophageal squamous cell carcinoma cohorts have histologically or cytologically confirmed metastatic disease and have tumors that are either immunotherapynaive with disease progression on 1 prior line of standard systemic therapy (cohort F) or immunotherapy-resistant with disease progression during or after 1 prior line of treatment that contained an anti-PD-1/PD-L1 therapy (cohort G). Patients must be aged at least 18 years, have measurable disease per RECIST v1.1 (verified by BICR) with no radiographic evidence of major blood vessel encasement or intratumoral cavitation, ECOG PS of 0 to 1, and an archival/new tumor sample for biomarker analysis. Patients in cohort F receive triple therapy with pembrolizumab plus lenvatinib plus belzutifan; patients in cohort G are randomized 1:1 to receive either the same triple therapy or doublet therapy with pembrolizumab plus lenvatinib. The planned starting doses are pembrolizumab 400 mg given intravenously every 6 weeks, lenvatinib 20 mg orally once daily, and belzutifan 120 mg orally once daily.

ESOPHAGEAL AND GASTRIC CANCER 105s

TPS427 Trials in Progress Poster Session

A randomized phase II/III study to evaluate the safety and efficacy of disitamab vedotin (DV) plus toripalimab and chemotherapy/trastuzumab as first-line treatment for HER2-expressed, locally advanced, or metastatic gastric cancer. First Author: Lin Shen, Department of GI Oncology, Peking University Cancer Hospital & Institute, Beijing, China Background: For HER2-positive (IHC 2+/FISH-, IHC 3+) advanced gastric cancer/ gastroesophageal junction cancer (GC/GEJ), trastuzumab in combination with chemotherapy is the standard first-line treatment. Adding pembrolizumab to trastuzumab and chemotherapy significantly improves objective response rate. However, the overall survival results did not meet statistical significance. DV, a novel humanized anti-HER2 antibody conjugated with monomethyl auristatin E (MMAE) via a cleavable linker. We aimed to evaluate DV combined with toripalimab and chemotherapy/ trastuzumab as first-line treatment for HER2-expressed (IHC 1+, 2+ or 3+) locally advanced or metastatic GC/GEJ. Methods: This is a randomized, seamless phase II/III trial. Key eligibility criteria include participants confirmed GC/GEJ and systemic treatment naïve. In phase II period, participants will be divided into two cohorts. Ninety participants with HER2positive (IHC2+ FISH+ or IHC3+) will be randomly (1:1:1) assigned to receive DV every 2 weeks (Q2W) plus toripalimab Q2W and oxaliplatin and capecitabine (CAPOX) every 3 weeks (Q3W), or DV plus toripalimab and trastuzumab Q3W, versus toripalimab plus trastuzumab and CAPOX. Forty participants with HER2-low (IHC1+ or IHC2+/FISH-) will be randomly (1:1) assigned to receive DV plus toripalimab and CAPOX, versus toripalimab and CAPOX. In phase III period, HER2-positive participants will be randomly (1: 1) assigned to receive DV plus toripalimab and CAPOX or trastuzumab versus CAPOX plus trastuzumab6anti-PD-1 antibody, based on results from phase II, and evolution of treatment landscape. HER2-low participants will be randomly (1:1) assigned to receive DV plus toripalimab and CAPOX versus CAPOX6anti-PD-1 antibody based on evolution of stand of care. The primary endpoint is PFS by IRC in PD-L1 CPS $5 population. Organ preservation with durvalumab-based immunotherapy in combination with chemoradiation as definitive therapy for early stage, cT1, and cT2N0 esophageal adenocarcinoma with indication for radical surgery: A prospective, multicenter study of the FLOT-AIO Gastric Cancer Group (IKF-t057/ PRESTO trial). First Author: Thorsten Goetze, Krankenhaus Nordwest, University Cancer Center Frankfurt, Frankfurt Am Main, Germany Background: The outcome of patients (pts) with adenocarcinomas of stomach and esophagogastric junction (GEJ) remains unsatisfactory (5-year survival rates of 24-84%), whereby surgical resection is considered as cornerstone of the curative treatment for pts with early stage esophageal adenocarcinoma (EGA), however, it is associated with mortality, morbidity and an impact on the patient's quality of life. Recent investigations showed that in locally advanced stage EGA surgery with neoadjuvant chemoradiotherapy (CROSS trial) is beneficial over surgery alone. Further benefit was achieved for locally advanced EGA by perioperative treatment with FLOT acc. to FLOT4trial data. Immuno-oncology (IO) therapy by using checkpoint inhibitors is approved in the palliative and adjuvant EGA situation. In this trial we aim for the organ preservation treatment of EGA pts with a combination of the anti PD-L1 antibody durvalumab-FLOTand chemoradio-therapy. Methods: The full, final text of this abstract will be available at meetings.asco.org on the day of presentation and in the online supplement to the January 20, 2024, issue of the Journal of Clinical Oncology.

Hepatic arterial infusion pump chemotherapy in patients with advanced intrahepatic cholangiocarcinoma confined to the liver: A multicenter phase II trial. First Author: Stijn Franssen, Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, Netherlands

Background: In the ABC-trials, the 3-year overall survival (OS) was only 2.8% for patients with advanced intrahepatic cholangiocarcinoma (iCCA) confined to the liver who received systemic gemcitabine with cisplatin. Hepatic arterial infusion pump (HAIP) combined with systemic chemotherapy had a pooled 3-year OS of 39.5% in a recent meta-analysis. HAIP chemotherapy involves continuous administration of floxuridine (FUDR) directly into the hepatic artery using a subcutaneous pump. The aim of this study was to prospectively assess the effectiveness of HAIP with systemic chemotherapy in patients with advanced iCCA confined to the liver in the Netherlands. Methods: We performed a single arm phase II trial in 3 centers in the Netherlands. Six cycles of HAIP chemotherapy with floxuridine were scheduled with 8 cycles of concurrent systemic chemotherapy with gemcitabine and cisplatin, if not administered previously. The primary endpoint was OS, secondary endpoints were progression-free survival (PFS) and objective response. Here we report updated clinical data and molecular correlates of response and resistance. Methods: Patients (pts) with previously untreated aBTC were randomized 1:1 to receive atezo (1200 mg every 3 weeks [q3w]) + bev (15 mg/kg q3w) or placebo (plb) + CisGem (Cis 25 mg/m 2 and Gem 1000 mg/m 2 on Days 1 and 8 q3w) for up to 8 cycles, followed by atezo (1200 mg q3w) + bev (15 mg/kg q3w) or plb until disease progression or unacceptable toxicity. The primary endpoint was progressionfree survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), duration of response (DOR), and safety. The final OS analysis was done when »90 deaths occurred or when all pts had $2 years of follow-up. Transcriptome analysis (n=98) and mutation profiling (n=103) were done on baseline tumor samples. This was a signal-seeking trial to estimate the treatment effect in each arm with no formal hypothesis testing.

Results: In total, 162 pts were randomized to either atezo + bev + CisGem (atezo/bev; n=79) or atezo + plb + CisGem (atezo/plb; n=83). The updated PFS HR was 0.67 (95% CI: 0.46, 0.95) in favor of atezo/bev. Updated median PFS was 8.35 mo for atezo/bev and 7.9 mo for atezo/plb, with 6-mo rates of 78% and 63%, respectively. The updated OS HR was 0.97 (95% CI: 0.64, 1.47), with a median of 14.9 mo for atezo/bev and 14.6 mo for atezo/plb. Confirmed ORR was 26.6% for atezo/bev and 26.5% for atezo/plb, with median DORs of 10.28 (95% CI: 6.7, 16.7) and 6.18 mo (95% CI: 4.3, 6.7), respectively. The incidence of Grade 3/4 adverse events was 73% with atezo/bev and 74% with atezo/plb. High VEGFA gene expression was associated with an improved PFS (HR, 0.43; 95% CI: 0.22, 0.83) and OS (HR, 0.66; 95% CI: 0.31, 1.4) in favor of atezo/bev. Hepatocytes high gene signature also was associated with an improved PFS (HR, 0.47; 95% CI: 0.24, 0.92) and OS (HR, 0.66; 95% CI: 0.31, 1.4) in favor of atezo/bev. Pts with PI3k/AKT pathway mutations appeared to have worse OS than pts without mutations (HR, 3.7; 95% CI: 1.5, 9.1) with atezo/bev. Conclusions: Final analysis of the IMbrave151 study indicates a modest PFS benefit in intent-to-treat pts combining atezo with bev and chemotherapy. The trial is limited by small numbers and a non-comparative design. Exploratory analysis of correlative biomarkers suggests that high VEGF-A gene expression and hepatocytes high gene signature may be predictive markers of benefit with atezo/bev, warranting further investigation. Clinical trial information: NCT04677504. Research Sponsor: F. Hoffmann-La Roche, Ltd.

108s HEPATOBILIARY CANCER Visit meetings.asco.org and search by abstract for the full list of abstract authors and their disclosure information.

Real-world clinical characteristics and treatment patterns among people with hepatocellular carcinoma in the United States (US) treated with resection or ablation. First Author: Neehar Parikh, University of Michigan, Ann Arbor, MI Background: Treatment guidelines for early-stage hepatocellular carcinoma (eHCC) include therapies with curative intent comprising three primary strategies: liver transplantation, surgical resection, or ablation (for small lesions). However, many people experience HCC recurrence, with recurrence rates of up to approximately 80% within 5 years after resection. Furthermore, contemporary insights into the eHCC treatment landscape and post-recurrence treatment patterns in the real-world setting are lacking. This study was designed to assess demographic and clinical characteristics and treatment patterns for people with HCC who received resection or ablation as a proxy for defining early-stage disease. Methods: This was a retrospective observational cohort study of adults with HCC treated with resection or ablation in the US, conducted using linked electronic health records and healthcare claims from Optum's de-identified Market Clarity Data. Index date was the date of the first observed resection or ablation between July 2016 and March 2021. Baseline characteristics were assessed in the 6-month period prior to index, and patients (pts) were followed until end of continuous enrolment in a medical and pharmacy plan, death, or data cut-off (September 2022), whichever occurred first. Demographic and clinical characteristics and treatment patterns, including subsequent treatments, were described. Results: A total of 649 pts met the study criteria and were included in the analyses. The median duration of followup was 23.0 months (range: 0.03-74.55 months). The mean age at index was 64.1 years (median 64.0 years), with a majority male gender (72.9%) and White race (65.5%). A total of 385 pts (59.3%) underwent ablation only, 242 pts (37.3%) underwent resection only, and 22 pts (3.4%) underwent both procedures at index. Transarterial embolization alone was received by 57 (8.8%) pts and was the most common embolization procedure received during follow-up, followed by transarterial chemoembolization alone in 46 (7.1%) pts and transarterial radioembolization in 46 (7.1%) pts. A total of 88 (13.6%) pts received systemic therapies for HCC (tyrosine kinase inhibitors, programmed cell death protein-1/programmed cell death-ligand 1/cytotoxic T-lymphocyte-associated antigen 4 inhibitors, or angiogenesis inhibitors) during follow-up. Conclusions: In this real-world cohort, ablation was the most received curative intent therapy for HCC. Among treatments received during follow-up, locoregional therapies were used most often, followed by systemic therapies. Although limited by its retrospective, observational nature, short duration of follow-up, and availability of data in the database, the results of this analysis provide a contemporary landscape of early-stage treatments for HCC in the real-world setting. Research Sponsor: AstraZeneca.

437 Poster Session

Prognostic

438 Poster Session

Impact of Hispanic ethnicity on immunotherapy outcomes in hepatocellular carcinoma: Insights from the National Cancer Database. First Author: Sumit Gaur, Texas Tech University Health Science Center, El Paso, TX Background: Hepatocellular carcinoma (HCC) is the fastest-growing cancer in the US with more age-adjusted incident cases in Hispanics compared to non-Hispanics. Immunotherapies are considered integral part of treatment for most unresectable HCC.

Recent multinational phase III trials suggest the benefit of immunotherapies may differ based on geographic region and underlying etiology of HCC. We hypothesized that Hispanic ethnicity might influence responses to immunotherapy in HCC. Methods: We analyzed the National Cancer Database (NCDB) to assess the impact of immunotherapy on overall survival (OS) in Hispanic patients with HCC. The database was queried for liver cancer from 2004 to 2020. Kaplan Meier method was used to assess OS and a log-rank test was used to compare survival distribution between Hispanic and non-Hispanic groups. Cox regression analysis was performed to estimate the adjusted effect of ethnicity on OS based on immunotherapy status. NCDB is a joint project of the Commission on Cancer (CoC) of the American College of Surgeons and the American Cancer Society. The CoC's NCDB and the hospitals participating in the CoC Õs NCDB are the source of the de-identified data used herein. Results: A total of 225079 patients were identified of whom 2036 patients (0.9%) received immunotherapy as first-line treatment. Patients with non-Hispanic ethnicity, male sex, who received treatment at academic/research institutions, and were insured were more likely to receive immunotherapy. In the entire cohort, there was no difference (p=0.94) in survival between those who did not receive immunotherapy (median OS,11.63 months; IQR: 2.79, 34.83) vs. those who did (median OS, 10.68 months, IQR: 5.19, 23.

29[DA2]

). There were more Hispanics in the cohort who did not receive immunotherapy (12.28% vs. 10.61%). In the adjusted Cox analysis, Hispanics had a reduced risk of death than non-Hispanics among patients who did not receive immunotherapy (HR: 0.873, 95%CI, 0.858-0.889; p,0.001). Among patients with immunotherapy, there was no OS difference between ethnicities (HR 0.904, 95% CI, 0.755-1.082; p 0.271). Conclusions: Hispanics were less likely to receive immunotherapy than non-Hispanics. Although Hispanics had a better OS than non-Hispanics among patients without immunotherapy, the differences no longer persist among patients who received immunotherapy. These findings suggest that Hispanic ethnicity may influence responses to immunotherapy. As compared to non-Hispanic whites, Hispanics with HCC have significantly more nonalcoholic fatty liver disease and alcohol-related liver disease as contributing factors. A better understanding of the impact of immunotherapies on alcoholic and nonalcoholic liver disease-related HCC is needed. Research Sponsor: None.

439 Poster Session

Relative and collective contribution of liver and bile duct cancer risk factors among minority groups in California. First Author: M. Cecilia Monge B., Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD Background: Liver and Bile Duct Cancer is a significant public health concern with higher incidence rates observed among people belonging to racial and ethnic minority groups compared to non-Hispanic White people. This study aims to understand which underlying factors contribute most to this disparity in liver and bile duct cancer. Methods: The California Health Maps database was analyzed from 2015-2019, including 58 counties: consistent with the SEER census and CDC PLACES Project. Variables examined included race, ethnicity, age, health insurance status, foreign-born status, rural residence, obesity prevalence, socioeconomic status, smoking status, and percentage of individuals receiving preventative care. Linear regression analysis was used to determine which factors significantly predict higher prevalence of liver and bile duct cancer. Results: The population consisted of 39,283,494 people, predominantly Hispanic (39%) with 38.7% being non-Hispanic White; 15.5% Asian or Pacific Islander and 6.2% non-Hispanic Black. Hispanic people accounted for 21% of the 868,882 total cancer cases and 33% of the 22,439 cases of liver and bile duct cancers reported. Race and ethnicity were the most substantial predictors of liver and bile duct cancer prevalence; counties with a higher monitory population exhibited higher incidence rates (Hispanic: R=0.39; p=0.003, Black: R=0.39; p=0.004, White: R=-0.55; p,0.0001, Asian: R=0.33; p=0.01).

Being foreign-born (R=0.45; p=0.0008), residing in non-rural areas (R= -0.33; p=0.01), and lacking preventative care (women: R= -0.30; p=0.03, men: R= -0.37; p=0.006) were also significantly associated with increased liver and bile duct cancer incidence rates (Table ). Conclusions: This study highlights the association of race, ethnicity, and access to healthcare services with higher incidence rates of liver and bile duct cancer among Hispanic and non-Hispanic Black people compared to non-Hispanic White people.

442 Poster Session

Efficacy of immune checkpoint inhibitors in patients with HIV-associated unresectable HCC (uHCC): Propensity-score matched analyses from two international consortia. First Author: Claudia A.M. Fulgenzi, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, United Kingdom

Background: HIV-associated HCC is an incompletely characterized disease with poor prognosis. People living with HIV (PWH) are commonly excluded from clinical trials, leading to a paucity of high-level evidence for optimal management. Whether ICIs are tolerated and effective in HIV-associated uHCC remains unclear. Methods: Using data from the CATCH-IT consortium and from a global dataset recruiting patients with HCC from 14 centers in 3 continents, we selected patients with HIV-associated uHCC treated with ICIs and compared their outcomes with a matched cohort of HIV negative (HIV-) patients. Primary endpoints were overall (OS) and progression-free survival (PFS). Propensity score matching (PSM) between the two groups was performed for the following variables: age, sex, HCC 16.6 [12.8, 18.7] Racial/ethnic disparities in the effectiveness of atezolizumab plus bevacizumab (A+B) vs. tyrosine kinase inhibitors (TKIs) among veterans with unresectable hepatocellular carcinoma (uHCC). First Author: David Edward Kaplan, Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA Background: The etiology of liver disease and HCC often differs by race and ethnicity, which may lead to potential differential effectiveness of immunotherapy (IO) by race/ethnicity. However, clinical trials for HCC have historically had limited racial diversity. Emerging data has characterized the real-world effectiveness of A+B, the standard of care for first-line (1L) uHCC. This study assessed whether there is racial/ethnic difference in the effectiveness of A+B compared to TKIs, including sorafenib (S) or lenvatinib (L). Methods: A population-based retrospective analysis was conducted using data from the Veterans Health Administration (VHA) Data Warehouse. Non-Hispanic White, African American (AA), and Hispanic patients diagnosed with uHCC between 2017 and 2022 who initiated 1L A+B (on or after 2020), S, or L were selected. Kaplan-Meier analyses and multivariable Cox regression analysis with race/ethnicity as a treatment modifier (adjusting for age, region, extrahepatic metastases, etiology, presence of cirrhosis, comorbidity index, prior local therapies, Child-Pugh [CP] class, and Albumin-Bilirubin [ABLI] grades) were conducted to investigate the racial/ethnic differences in the effectiveness of A+B vs S or L. Results: Of 1,738 patients, 1,140 were White (20% A+B, 56% S, 24% L), 437 were AA (25% A+B, 50% S, 25% L), and 161 were Hispanic (22% A+B, 57% S, 21% L). Compared to Whites, a significantly higher proportion of AAs had underlying hepatitis C (87% vs 56%, p,0.05). There was a trend towards a lower proportion of CP B and C and less ascites in AAs compared to Whites. Table shows median OS (mOS) by race and regimen, along with hazard ratios (HRs) from the multivariate analysis. The survival benefit associated with A+B compared with S or L was numerically greater in AA patients versus White patients, although the difference did not achieve statistical significance. Conclusions: In this realworld cohort of 1L uHCC patients, A+B demonstrated a significant survival advantage over TKIs across racial/ethnic groups. Understanding the factors contributing to the effectiveness of A+B across racial/ethnic groups could provide valuable insights for guiding future trials and initiatives aimed at addressing racial disparities in HCC. Research Sponsor: F. Hoffman La Roche.

All

451 Poster Session

Real-world correlation of RFS and OS in early-stage hepatocellular carcinoma treated with curative intent: A retrospective analysis of SEER-Medicare data. First Author: Neil Mehta, University of California, San Francisco, San Francisco, CA

Background: Curative intent therapy with resection or ablation for early-stage HCC is associated with high incidence of recurrence. Effective adjuvant therapy is needed to improve outcomes. While OS is the preferred endpoint for demonstrating efficacy of new adjuvant therapies, recurrence-free survival (RFS) may better reflect the benefits associated with adjuvant therapy due to being independent of subsequent therapies upon recurrence. Additionally, RFS may provide insights into patient (pt) outcomes while OS data are immature. We assessed the correlation between OS and RFS in pts with early-stage HCC after treatment with curative intent.

Methods: This study used the SEER-Medicare database (2007) (2008) (2009) (2010) (2011) (2012) (2013) (2014) (2015) (2016) (2017) The REFINE real-world study (NCT03289273) assessed a more varied pt population treated with regorafenib than the phase 3 RESORCE trial. 1 Median overall survival (OS) in REFINE was 13.2 months and treatment-emergent adverse events (TEAEs) were consistent with RESORCE. We present a subgroup analysis of outcomes in pts from REFINE with CP-B liver function. Methods: REFINE is an international, prospective observational study of pts with uHCC for whom the decision to treat with regorafenib according to the local health authority approved label was made by their physician before enrollment. The primary endpoints were safety (Medical Dictionary for Regulatory Activities v25) and dose modifications due to drug-related TEAEs. Secondary endpoints included OS and duration of treatment (DoT). Results: Of 1005 evaluable pts, 123 (12%) were classified as CP-B at study entry, with most being CP-B7 (Table ). Of the CP-B pts, 40/123 (9%), 9/123 (18%), and 58/123 (15%) initiated regorafenib at 160 mg, 120 mg, and 80 mg, per day, respectively. Median DoT with regorafenib was 2.3 months in CP-B pts and 3.7 months in the overall cohort. Incidence rates of TEAEs in CP-B pts and the overall cohort were similar (93% and 92%) and TEAEs were drug-related in 70% and 74% of pts, respectively. Grade 3-4 TEAEs occurred in 41% of CP-B pts and 39% of the overall cohort and were drug-related in 27% and 26% of pts, respectively. Serious TEAEs were observed in 48% of CP-B pts and 37% of the overall cohort, and were drug-related in 11% and 9% of pts, respectively. Drug-related TEAEs led to less frequent dose modifications in CP-B pts than in the overall cohort (28% vs 37%), but more frequent permanent discontinuations (28% vs 16%). Median OS in CP-B pts was 6.

459 Poster Session

Clinical characteristics and the course of hepatobiliary and pancreatic malignant tumors with high microsatellite instability after pembrolizumab administration: A multicenter observational study. First Author: Yuta Maruki, Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan

Background: The Keynote-158 trial have resulted in an expanded approval for pembrolizumab (Pem) in solid tumors with high microsatellite instability (MSI-H). In the trial, Pem was administered to patients with MSI-H solid tumors, excluding colorectal cancer, and the overall response rate (ORR) was 34%. However, the ORR for pancreatic (PANC) and biliary tract (BT) cancer were 19% (4/22 cases) and 41% (9/22 cases), respectively, suggesting the possibility of varying treatment efficacy by the primary tumor site. In this study, we aimed to clarify the clinical characteristics of patients with MSI-H and the efficacy of Pem administration in hepatobiliary and pancreatic (HBP) cancers.

Methods: A multicenter observational study of patients with HBP cancer with MSI-H was conducted from March 2020 to March 2023. This study consists of prospective and retrospective cohorts. We evaluated the efficacy of PEM administration in patients with PANC and BT, respectively. Results: We enrolled 51 patients, including 32 in the prospective cohort; males comprised 51% of the patients. The BT, PANC, and liver were the primary sites in 26, 24, and 1 patients, respectively. MSI-H diagnostic methods were the MSI kit (FALCO) and comprehensive genome profile in 43 (84%) and 8 (16%) patients, respectively. Intrahepatic cholangiocarcinoma (ICC) was the most common cancer in BT tumor; ICC was observed 13 (50%) patients, followed by perihilar, gallbladder, and distal bile duct (including ampullary cancer) cancers in 6, 4, and 3 patients, respectively. Some rare histological types were observed, two patients had neuroendocrine carcinoma and one had hepatoid carcinoma in PANC. One had an undifferentiated carcinoma in BT. Five and six patients with PANC and BT tumors, respectively, had one or more first-degree relatives with lynch syndrome-related disease. Pem was administered to 96% and 88% of the patients with PANC and BT tumors, respectively. The ORR was 30% in PANC and 73% in BT tumors (p=0.003). In BT tumor, three patients demonstrated complete response as follows: two with ICC and one with perihilar cholangiocarcinoma. The median progression-free survival was 3.2 months (95% confidence interval [CI], 1.3-14.4) and 16.3 months (95% CI, 8.7 to not reached) in patients PANC and BT tumors (p=0.08), respectively. Grade 3/4 immune-related adverse events occurred in 13% and 29% of the patients with PANC and BT tumors, respectively. Conclusions: ICC was the most common BT cancer with MSI-H. Pem was significantly more effective in BT tumors than in PANC tumors, with higher ORR. Clinical trial information: UMIN000040591. Research Sponsor: None.

Outcomes and prognostic factors of advanced biliary tract cancers in Saudi Arabia. First Author: Kanan Alshammari, Oncology Department, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia Background: Biliary tract cancers which include gallbladder adenocarcinoma, intrahepatic and extrahepatic cholangiocarcinoma are rare, and carry a poor prognosis. There is limited data on biliary tract cancers in the Saudi population. Methods: This single center retrospective study was conducted with data of eligible cases from the last 4 years. Survival, chemotherapy regimens, and variables such as neutrophil to lymphocyte ratio (NLR), and other potential prognostic variables were collected. Results: The study included 155 patients of which 75 had intrahepatic cholangiocarcinoma and 74 had gallbladder adenocarcinoma. The majority were females at 63% of patients. Overweight to obese patients represented 59% of the study cohort. The majority of patients (62%) had an ECOG performance status of 2 and below. Comprehensive genomic profiling was done to 20% of cholangiocarcinoma cases. Elevated CA19-9 tumor marker (. 37 micromol/L) was found in 57% of patients. De novo metastatic disease affected 82% of patients. One third of patients (33%) were not fit for first line chemotherapy, and were given best supportive care. First line chemotherapy of platinum + gemcitabine was given to 53% of fit patients, followed by gemcitabine alone given to 38%, followed by 5-Fluorouracil chemotherapy given to 9% of patients. Very few patients lived for 12 months or more at 16%. There was a significant association between NLR and progression free survival (PFS) with median PFS being 3.5 months in the NLR . 3 group (95% CI 1.2-6 months) versus median PFS of 9.8 months in the NLR , 3 group (95% CI 7.5-12 months, p=0.019). Conclusions: Biliary tract cancers still carry a poor prognosis. NLR ratio of more than 3 was found to predict a low PFS. Research Sponsor: None.

461 Poster Session

Real-world use of pemigatinib (pemi) for cholangiocarcinoma (CCA) among racial and ethnic minorities in the United States. First Author: Richard D. Kim, Moffitt Cancer Center, Tampa, FL Background: Pemi received accelerated approval by the FDA in 2020 for treatment of patients (pts) with unresectable locally advanced or metastatic CCA with a fibroblast growth factor receptor 2 (FGFR2) fusion or other FGFR2 rearrangement. A recent real-world study (RWS; submitted to ASCO-GI 2024) assessing characteristics, FGFR2 testing patterns, treatment patterns, and outcomes of pts treated with pemi for locally advanced or metastatic CCA in the US as part of routine clinical care found substantial racial and ethnic diversity in pts treated with pemi. The purpose of this analysis is to describe the findings of the pemi RWS for CCA by race and ethnicity. Methods: This was a retrospective cohort study in which US-based participating physicians from Cardinal Health's Oncology Provider Extended Network abstracted data from eligible pts' medical records into electronic case report forms. Eligible pts were $18 years of age, initially prescribed pemi for unresectable locally advanced or metastatic CCA on or after 4/17/2020, and had $4 mo of follow-up (unless ,4 mo due to death). Pts who did not receive pemi or had received pemi in a clinical trial or systemic therapy for another primary malignancy (except for cancer of unknown primary or hepatic cancer) were excluded. Results were summarized by race (White, Black/African American, "Other" [pts with mixed race or a race other than White, Black/African American, or Unknown]) and ethnicity (Non-Hispanic, Hispanic) using descriptive statistics. Results: 18 physicians abstracted data for 120 eligible pts. Median follow-up from initial pemi prescription was 6.5 mo, at which time 71 pts (59%) were alive and 60 (50%) were still receiving pemi. The racial makeup of the study population was 55% White, 21% Black, 18% Other, and 7% Unknown. Ethnic composition was 78% Non-Hispanic, 19% Hispanic, and 3% Unknown. Key results are presented in the 97 ) 24 ( 96 ) 17 ( 81 ) 91 ( 97 ) 19 ( 83 ) Received pemi as 2nd-Line therapy, n (%) 62 ( 94 ) 22 ( 88 ) 21 ( 100 ) 89 ( 95 ) 21 ( 91 ) Disease response available, n (%) 63 ( 95 ) 24 ( 96 ) 21 ( 100 ) 90 ( 96 ) 23 ( 100 BL, baseline (date of 1st pemi prescription); CI, confidence interval; FGFR2, fibroblast growth factor receptor 2; P25-P75, 25-75th percentile; rwORR, real-world overall response rate; y, years.

462 Poster Session

The impact of CARE Frailty Index on overall survival in older adults with hepatocellular carcinoma. First Author: Ahmet Anil Ozluk, Division of Hematology/ Oncology/O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL

Background: Pre-treatment frailty is associated with unfavorable short and long-term outcomes among patients with hepatocellular cancer (HCC) post liver resection.However, there is a knowledge gap in identifying the subset of older adults with HCC at high risk for inferior survival outcomes. Methods: We evaluated the association between patient-reported geriatric assessment (GA)-based frailty index and overall survival (OS) among older adults ($60y) diagnosed with HCC enrolled in a single institutional prospective registry (Cancer and Aging Resilience Assessment (CARE) registry). All patients underwent a patient-reported GA at enrollment that encompassed multiple health domains related to aging. To determine frailty, we utilized a 44-item CARE Frailty Index (CARE-FI) based on the principles of deficit accumulation (Giri S et al JAGS 2021) . We categorized frailty into robust, pre-frail and frail. The primary outcome was OS from the time of GA. Comparison of survival between groups was made using logrank statistic. A multivariable Cox regression model measured the independent association between frailty and OS adjusted for age, etiology, Child-Pugh score and cancer stage. Results: A total of 116 older adults with HCC were identified with a median follow-up 2.1 year, median age was 67y (63-72) with 82% males, 27% blacks, 64% with Child-Pugh-A and 78% with stage III/IV disease. Overall, 50.1% (n=58) were frail, 33.6% (n=39) pre-frail and 16.3% (n=19) robust. No significant clinico-demographic differences across the 3 frailty groups were observed. In univariable analysis, there was a marginally significant difference between the three frailty groups (p value 0.06). However, in multivariable analysis, being frail vs robust was associated with an increased risk of mortality

465 Poster Session

Care delivery and patient self-management for people with primary liver cancer receiving 4R care sequence plans. First Author: George Therapondos, Department of Gastroenterology and Multiorgan Transplant Institute, Oschner Medical Center, New Orleans, LA Background: The 4R Oncology Model (4R=Right information/care/patient/time) supports patient self-management 1 and quality improvement. 2 Here we report the impact of using 4R Care Sequence plans for patients with primary liver cancer cared for by a multi-disciplinary liver cancer team. Methods: We tested the impact of 4R care sequence plans on patient selfmanagement and care delivery referrals at a liver cancer program via patient surveys. 4R Plans were provided to patients with primary liver cancer from Jan -Aug '23 (4R cohort). Patientreported data were analyzed to compare the control cohort of patients who received care pre-4R, Jan -Dec '22 (N=42) to the 4R cohort (N=17). Statistical analysis used Fisher's exact test.

Results: Patient survey response rates: Control cohort 54% (42/78), 4R cohort 55% (17/31).

Comparing the control cohort to the 4R cohort respectively, patients were male (52%, 65%), White (64%, 64%), Black (26%, 18%), average age (63.2, 64.7), and reported income less than $30,000 (45%, 53%). The 4R cohort significantly improved care delivery in three metrics, and directionally improved in the other care delivery metrics as compared to the control cohort (table ). All four patient self-management metrics significantly improved in the 4R cohort vs. the control cohort (Table ). Conclusions: The use of 4R Care Sequence plans for patients with primary liver cancer facilitated improvements in care delivery and patient self-management metrics. While there were directional improvements in all metrics, there is opportunity and room for additional improvements. The team will continue to work on efforts to improve these metrics and optimize the use of 4R Care Sequence plans for patients with primary liver cancer.

467 Poster Session

Organ-specific response with first-line atezolizumab-bevacizumab versus lenvatinib for patients with advanced hepatocellular carcinoma. First Author: Young-Gyu Park, Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea Background: Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related death worldwide. Immune checkpoint inhibitor (ICI)-based treatments have become the mainstay of first-line treatment for unresectable HCC, but there has been a concern that intrahepatic HCC lesions may be less responsive to ICI monotherapy. Methods: This retrospective study included 386 patients with Child-Pugh A unresectable HCC who were treated with first-line atezolizumab-bevacizumab (n = 217) or lenvatinib (n = 169). The organ-specific response was separately evaluated according to the site of the lesions: liver, lung, lymph node (LN), and intra-abdomen based on a radiological evaluation adopted from RECIST v 1.1. Up to 2 lesions were chosen as target lesions in each organ for the organ-specific response evaluation. Results: The median age was 60 years. The majority of study patients were male in both groups (83.4% and 85.8% in the atezolizumab-bevacizumab and lenvatinib groups, respectively). The etiology of HCC was similar between the two groups: hepatitis B virus infection was the most common etiology in both groups (73.3% and 65.7% in the atezolizumab-bevacizumab and lenvatinib groups, respectively), while 21.2% and 29.0% of patients had non-viral HCC, respectively. Extrahepatic spread was identified in 76.0% and 74.6% of patients in the atezolizumab-bevacizumab and lenvatinib groups, respectively: lung, LN, and intra-abdominal metastases were present in 39.6% vs. 39.1%, 30.0% vs. 33.1% and 16.6% vs. 15.4% of patients, respectively. The proportion of patients achieving a $ 30% reduction in the tumor burden for each organ category was higher overall in the atezolizumab-bevacizumab group than in the lenvatinib group: 20.2% vs. 11.8%, 23.0% vs. 12.2%, 27.9% vs. 17.9%, and 33.3% vs. 15.0% for intrahepatic, lung, LN and intra-abdominal lesions, respectively. The corresponding values for the subgroup with a viral etiology were 17.3% vs. 8.1%, 18.8% vs. 13.3%, 28.9% vs. 3.6% and 36.0% vs. 12.5%, respectively. Among patients with a non-viral etiology, atezolizumab-bevacizumab was not clearly associated with a better organ-specific response for the LN and intra-abdominal lesions: 20.0% vs. 54.5% and 20.0% vs. 25.0%, respectively, for a $ 30% reduction in the tumor burden. Conclusions: Compared to lenvatinib, atezolizumab-bevacizumab was associated with a favorable organ-specific response regardless of the site of the tumor lesions. Unlike anti-PD-1 monotherapy, atezolizumab-bevacizumab had a comparable organ-specific response between intrahepatic and extrahepatic lesions, especially for those with viral etiology HCCs. Research Sponsor: None.

116s HEPATOBILIARY CANCER Visit meetings.asco.org and search by abstract for the full list of abstract authors and their disclosure information.

Preoperative endoscopic biliary drainage procedures may affect intrahepatic recurrence of cholangiocarcinoma after surgical resection. First Author: Jin-Oh Kim, Soonchunhyang University Seoul Hospital, Yongsan-Gu, South Korea Background: To determine the impact of preoperative endoscopic nasal biliary drainage (ENBD) and/or endoscopic retrograde biliary drainage (ERBD) procedures on intrahepatic recurrence rate in patients with cholangiocarcinoma after surgical resection. Methods: Between January 2005 and January 2023, 143 patients diagnosed cholangiocarcinoma and received surgical resection. Among 143 patients, 99 patients were treated with preoperative ENBD and/or ERBD. We retrospectively analysed prognostic factors (age, gender, preoperative ENBD and/or ERBD, tumor differentiation, pT factor, lymph node metastasis, surgical margin, lymphovascular invasion, preoperative maximal total bilirubin, postoperative chemoradiation/chemotherapy/radiation therapy, CA19-9) for recurrence after surgical resection. Results: Intrahepatic recurrence after surgical resection was detected in 22 /99(22.2%) patients with preoperative ENBD and/or ERBD, and 5/44(11.4%) patients without preoperative ENBD and/or ERBD for median period of 12 months (range 0-48). On univariate analysis, intrahepatic recurrence rate of patients who underwent ENBD and/or ERBD (n=99) was higher than that of patients who did not (n=44) (P=0.090) and and that of patients who had T3/T4 factor (n=74) was higher than that of who had T1/T2 factor (n=69) (P=0.168). Intrahepatic recurrence rateof patients who had elevated CA19-9 (. 200) (n=49) was higher than that of patients who had not (n=94) (P=0.002

474 Poster Session

Continuation rather than early induction in S-1 adjuvant chemotherapy and prognosis in patients after biliary tract cancer resection. First Author: Kotaro Hayashida, Nagasaki University Hospital, Nagasaki, Japan

Background: The efficacy of S-1 monotherapy as adjuvant chemotherapy (AC) for pancreatic cancer has been demonstrated, and the long-term results are clearly improving. 1 In biliary tract cancer, the JCOG1201 trial in Japan also demonstrated the usefulness of S-1 AC recently. 2 We have been also performed S-1 AC for biliary tract cancer in recent years in accordance with the clinical necessity. In this article, we herein retrospectively analyze the S-1 AC for biliary tract cancer especially in the significance of initiation day or therapy continuation. Methods: 134 patients with the resection of biliary tract cancer (intrahepatic cholangiocarcinoma 25/ hilar 17/ gallbladder 27/ distal bile duct 38/ papillary 25 from January 2017 to December 2021 were included in this study. Age 73(30-87) years, 47 hepatic resections/66 pancreatecticoduodenectomies/ 21 peri-gallbladder resection. The decision to administer AC was made at the discretion of the attending doctor and in consultation with the patient, and the decision to discontinue was based on the patient's physical condition. If there was no particular need to discontinue, the treatment was continued for six months at least. Results: S-1 AC was performed in 57/137 (43%) of eligible patients. Age was similar between with or without AC patients (73 vs. 73 years old). There were no significant differences by the cancer location. Although pathological stage was higher in the patients with AC (stage 0:1:2:3:4 = 0: 20: 39: 31: 9%) than without AC ( = 9: 45: 33: 10: 3%) (p , 0.001), 2 years recurrence free survival (2y-RFS) was similar between with AC or without AC patients (66.6 vs 71.6%, p=0.82). In the subgroup analysis of the patients with AC, although comparisons of induction day of AC within or after postoperative 6 weeks showed no difference in patient's prognosis, patients with continuation of AC for at least 6 months after initiation clearly had a better prognosis than without it (2y-RFS: 89.6 vs 41.7%, p=0.003).

Conclusions: In S-1 AC for the patients after biliary tract cancer resection, early induction does not play much role, but continuation is important to maintain better prognosis. 1. Uesaka et al. Lancet, 2016 . 2. Nakachi et al. Lancet, 2023. Research Sponsor: None.

475 Poster Session

ZSAB-TOP: A phase 2 trial of tislelizumab (TIS) and ociperlimab (OCI) combined with gemcitabine and cisplatin (GemCis) as the first-line treatment for advanced biliary tract cancer (BTC). First Author: Jia Fan, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China

Background: GemCis has long been the standard-of-care for advanced BTC, however the prognosis remains poor. Combinations with immunotherapy and GemCis are being explored in BTC. This study aimed to evaluate the efficacy and safety of TIS (an anti-PD-1 antibody) and OCI (a TIGIT inhibitor) combined with GemCis as the first-line treatment for advanced BTC. Herein, the primary analysis results of this study were reported. Methods: In this open-label, single-arm, multicenter phase 2 study, systematic treatment-naïve pts with unresectable advanced BTC received TIS (200 mg, day1, Q3W), OCI (900 mg, day1, Q3W), and GemCis (Gem 1000 mg/m 2 and Cis 25 mg/m 2 on days 1 and 8 Q3W, up to 8 cycles). The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. A binomial exact test with a one-sided a of 0.05 was performed in the analysis of the primary endpoint to test the historical ORR of 25% with GemCis. If p#0.05, the statistical superiority of the study treatment would be claimed. Results: A total of 45 pts were enrolled, with 75.6% having intrahepatic cholangiocarcinoma and 60.0% metastatic disease. As of 24 Aug 2023 (median follow-up, 8.0 months), 24.4% (11/45) pts remained on study treatment. Among the 41 pts in efficacy analysis set, confirmed ORR (cORR) was 48.8% (20/41, 95% CI, 32.9-64.9, p=0.0009), with 1 complete response. The statistical superiority was achieved. The subgroups of TIGIT + pts tended to have numerically higher cORR (Table ). Median PFS was 7.7 months, with 6-month PFS rate of 67.6%. Median OS was not reached, and 6-month OS rate was 86.2%. Grade $3 treatment-related adverse events rate was 60% (27/45). Immune-mediated adverse events rate was 37.8% (17/45), which were mostly grade 1 and 2. Conclusions: The combination of TIS and OCI plus GemCis showed promising anti-tumor activity with manageable safety as the first-line treatment for advanced BTC. Clinical trial information: NCT05023109. Research Sponsor: None.

Overall efficacy (efficacy analysis set*, N=41).

cORR, % (95% CI) 48.8 (32.9-64.9) DCR, % (95% CI) 82.9 (67.9-92.

479 Poster Session

Clinical impact on treatment effectiveness of immune-related adverse events in patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab. First Author: Keito Suzuki, Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino-Shi, Tokyo, Japan Background: Immune checkpoint inhibitors (ICIs) have emerged as the first-line therapy for unresectable hepatocellular carcinoma (HCC). However, their administration poses the risk of immune-related adverse events (irAEs). Recent data suggests that the occurrence of irAEs may be associated with a favorable prognosis. Nevertheless, limited studies have explored the relationship between irAE severity or specific symptoms and clinical outcomes. Therefore, the objective of this study was to investigate and analyze the association between these adverse events and the clinical benefits in patients with unresectable HCC treated with immune checkpoint inhibitors. Methods: We enrolled 130 patients with unresectable HCC treated with atezolizumab plus bevacizumab between November 2022 and January 2023 at a single center. We investigated the relationship between irAEs and both response rate and post-treatment outcomes.

Results: Out of the 130 patients, 36 (27.7%) developed irAEs. Patients with irAEs exhibited a significantly longer progression-free survival (PFS) compared to the non-irAE group, with a median PFS of 8.9 months compared to 4.6 months (p , 0.01). There was no difference in overall survival with or without irAEs. The irAE group demonstrated significantly higher disease control rate (DCR) compared to the non-irAE group (97.0% vs 65.5%, p , 0.01). The analysis by the severity of irAE revealed that the grade 1/2 group exhibited significantly longer PFS (7.9 months vs 4.6 months, p =0.007) and higher DCR (100% vs 65.5%, p , 0.01) compared to the non-irAE group. Furthermore, hypothyroidism was correlated with a favorable PFS (8.9 months vs 5.4 months, p = 0.02), DCR (100% vs 71.3%, p = 0.03) and overall response rate (58.3% vs 18.5%, p = 0.005).

The presence of irAEs is associated with prolonged PFS and higher DCR. Specifically, mild irAEs (Grade 1/2) and hypothyroidism displayed prolonged PFS and higher DCR.

482 Poster Session

Lenvatinib plus pembrolizumab versus lenvatinib alone as first-line therapy for advanced hepatocellular carcinoma: Longer-term efficacy and safety results from the phase 3 LEAP-002 study. First Author: Richard S. Finn, University of California, Los Angeles, Los Angeles, CA Background: The randomized, double-blind, phase 3 LEAP-002 study (NCT03713593) was conducted to evaluate the efficacy and safety of first-line (1L) lenvatinib (len) + pembrolizumab (pembro) vs len + placebo (pbo) in patients (pts) with advanced hepatocellular carcinoma (HCC). After a median follow-up (randomization to data cutoff) of 32.1 mo, LEAP-002 did not meet its primary end points of OS at final analysis (median, 21.2 vs 19.0 mo; HR, 0.840; 95% CI, 0.708-0.997) and PFS at interim analysis 1 (IA1; median, 8.2 vs 8.0 mo; HR, 0.867; 95% CI, 0.734-1.024). However, the study highlighted the activity of len + pembro and, given the late separation of Kaplan-Meier survival curves for OS and PFS between treatment arms from 12 mo onwards, outcomes with extended follow-up are of interest. We report results after 12 mo of additional follow-up (median 43.6 mo). Methods: Eligible pts with advanced HCC were randomized 1:1 to len ( 8

483 Poster Session

Treatment outcomes by stratifying the N-acetyl transferase 2 phenotype in pre-treated patients with advanced refractory biliary tract cancer treated with nanvuranlat, an L-type amino acid transporter inhibitor: An ad-hoc analysis of a randomized, double-blind, placebo-controlled phase 2 study. First Author: Naohiro Okano, Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan

Background: L-type amino acid transporter 1 (LAT1, SLC7A5) is overexpressed in cancer cells, leading to aggressive proliferation and lymphatic metastases. In a placebo-controlled, randomized phase 2 trial involving patients with pre-treated, advanced, refractory biliary tract cancer (BTC), monotherapy with nanvuranlat (JPH203), a selective LAT1 inhibitor, demonstrated a significant improvement in progression free survival (PFS) as the primary endpoint compared to placebo. The safety profile was comparable between nanvuranlat and placebo treated patients, except for a higher rate of cholangitis in the nanvuranlat group. Nanvuranlat is metabolized to its main inactive, off-target metabolite, Nac-JPH203 by N-acetyl transferase 2 (NAT2). Since the NAT2 unknown patients mislead the benefit and risk ratio of nanvuranlat treatment, an ad-hoc analysis was conducted in enriched NAT2 non-rapid (NR) phenotype patients who slowly produced Nac-JPH203 in plasma. Methods: Among 104 (full analytical set (FAS) -nanvuranlat:69 & placebo:35) enrolled patients, 25 with unknown NAT2 phenotype were enrolled prior to an amendment to only enroll NAT2-NR phenotype. Subsequently, further analysis was conducted to determine the NAT2 phenotypes of these 25 patients. Results: Among the 25 NAT2 unknown patients, 16 and 9 patients were assigned to nanvuranlat or placebo, respectively. NAT2 ad hoc analysis recorded those 9 patients in nanvuranlat and 5 in placebo as NAT2 NR, and 7 patients in nanvuranlat and 4 in placebo were NAT2 rapid (R). As a result, number of NAT2 NR patients was increased from 81 to 94. Efficacy analysis of this enriched population (FAS-NR-nanvuranlat:63 & placebo:31) revealed a significant improvement in PFS. With respect to cholangitis, 8 all-grade (12.7%) and 7 over grade 3 (11.1%) were documented in the FAS-NR population. In the FAS-R population, 2 all grades (28.5%) and 2 over grade 3 (28.5%) were observed (Table ). Conclusions: By classifying BTC patients by NAT2 phenotype in this ad hoc analysis, the LAT1 inhibitor nanvuranlat further improved its clinical efficacy and safety in the NAT2 NR population. Therefore, selecting NAT2 NR for nanvuranlat treatment may improve the risk -benefit ratio.

485 Poster Session

Defining ablative radiotherapy in patients with hepatocellular carcinoma: An expert consensus. First Author: Ted K. Yanagihara, The University of North Carolina at Chapel Hill, Chapel Hill, NC Background: External beam radiotherapy (EBRT) is a highly effective treatment in select patients with hepatocellular carcinoma (HCC). However, there are many types of EBRT described in the literature with no formal definition of what constitutes "ablative." Thus, we convened a group of international experts to provide consensus on the parameters that define ablative EBRT in HCC. Methods: A Steering Committee was convened to generate a series of Key Criteria (KC) that could be used to define ablative EBRT for HCC. KC were based on factors related to dose, fractionation, radiobiology, target identification, and delivery technique. An international panel of experts participated in a modified Delphi (mDelphi) process to independently answer questions for each KC.

Respondents were given 30 days to respond in round 1 of the mDelphi and 14 days to respond in round 2. A threshold of $ 70% was used to define consensus for answers to each KC. Results: Invitations were sent to 40 individuals and 35 (88%) returned responses. In the first round of the mDelphi, 3 of 7 KC reached consensus. In the second round, 100% of participants returned responses and consensus was reached in 3 of the remaining 4 KC. Based on this mDelphi analysis, there was expert agreement that ablative EBRT for HCC should be defined as 1) a BED 10 $ 80 Gy, 2) daily imaging and multi-phasic contrast used for target delineation should be used, 3) treatment breaks (e.g., for adaptive EBRT) are allowed, but the total treatment time should be # 6 weeks, 4) the equivalent dose when treating with protons should use a conversion factor of 1.1, and 5) there is no single conversion factor for carbon ions. In one KC, which questioned the expert's opinion on the a/b ratio of HCC, consensus was not achieved.

Conclusions: Using an mDelphi method assessing expert opinion, we provide the first consensus definition of ablative EBRT for HCC. Empiric data are required to define the a/b of HCC. Research Sponsor: None.

486 Poster Session

Efficacy and safety of surufatinib in biliary tract cancer: Preliminary results of a real-world study. First Author: Zongli Zhang, Qilu Hospital of Shandong University, Jinan, Shandong, China

Background: When applied in the second-line treatment for biliary tract cancer (BTC) pts, surufatinib (a small-molecule inhibitor of VEGFR1-3, FGFR1 and CSF-1R) monotherapy has demonstrated moderate clinical efficacy and has demonstrated favorable tolerability and safety profiles. This study was to evaluate the efficacy and safety of surufatinib as a therapy for BTC in a real-world setting. In particular, pts who received resection for BTC with positive margins would be eligible for this study. This population indicates a poor prognosis, for their tumor environment is complex, which is an obstacle to R0 resection. However, no proper treatment for this population has been recommended yet. Methods: This is an ongoing single-arm, multi-center, open-label real-world study conducted in China. The study would enroll 200 pts with unresectable or surgical resection with positive margins BTC. Pts would receive surufatinib with or without combination as adjuvant (namely pts with positive margin after resection), first-or further-line therapy, at a proper dose (200-300mg) judged by physicians once per day in 28-day cycles. The primary endpoint is relapse-free survival (RFS) for pts whose primary lesions were resected, and progression-free survival (PFS) for those had evaluable lesions. If available, tumor assessments were performed every 2 cycles 6 7 days according to RECIST version 1.1. Results: By Sep 10, 2023, 56 eligible pts had been enrolled, of whom 16 (28.6%) were female. The median age was 64 (range: 39-81). 28 (50.0%), 24 (42.9%), and 4 (7.1%) pts received surufatinib as adjuvant, first-line, and above treatment, respectively. As to location, 23 cases were intrahepatic cholangiocarcinoma (ICC), and 33 cases were extrahepatic cholangiocarcinoma (ECC) or gallbladder cancer (GBC). With a median follow-up time of 9.5 (range: 1.1-20.3) mo, the global mRFS/mPFS was 10.4 (95% CI: 9.0-13.9) mo. The mRFS of pts who received surufatinib as adjuvant treatment was 11.3 (95% CI: 10.4-NA) mo, and mPFS of those who received surufatinib as systematic treatment was 9.0 (95% CI: 7. Background: Outcomes remain poor for pts treated with standard-of-care chemotherapy for advanced biliary tract cancer (BTC). Hence, there is a clinical need for novel therapeutic strategies. One such emerging strategy is antagonism of mouse double minute 2 (MDM2), which is amplified in 5-8% of cases of BTC. Brigimadlin (BI 907828) is a MDM2-p53 antagonist that blocks the MDM2-p53 interaction, thereby restoring p53 activity and leading to cell-cycle arrest and apoptosis in TP53 wild-type tumors. Brigimadlin is currently being assessed in two Phase Ia/Ib dose-escalation/expansion trials in pts with advanced/metastatic solid tumors as monotherapy (NCT03449381) and in combination with an anti-PD-1 antibody, ezabenlimab (NCT03964233). Here, we present data in pts with advanced BTCs treated in these trials. Methods: Pts in the monotherapy trial received escalating doses of brigimadlin on day 1 of 21-day cycles (Q3W). Pts in the combination trial received escalating doses of brigimadlin and 240 mg ezabenlimab on day 1 Q3W (doublet); one pt also received the anti-LAG-3 antibody BI 754111 (which has since been discontinued; triplet). Results: At data cut-off (June 2023), a total of 16 pts with BTC have been enrolled (10 in the monotherapy and 6 in the combination trial). In the monotherapy trial, 9 pts received brigimadlin 45 mg Q3W and 1 received 80 mg Q3W. In the combination trial, 5 pts received 30 mg/45 mg brigimadlin doublet and 1 received 45 mg triplet. Across both trials, 7 pts with MDM2-amplified tumors achieved partial response (PR), 3 in the monotherapy trial and 4 in the combination trial. In the monotherapy trial, the responding pts had intrahepatic cholangiocarcinoma (iCC; 80 mg, 73% tumor shrinkage, progression-free survival [PFS] 13.3 months), ampullary adenocarcinoma (45 mg, 72% tumor shrinkage, PFS censored at 666 days), and extrahepatic cholangiocarcinoma (45 mg, 68% tumor shrinkage, PFS censored at 164 days). In the combination trial, 3 responding pts had iCC (pt 1, 30 mg doublet, 54% tumor shrinkage, PFS 9.6 months; pt 2, 45 mg doublet, 49% tumor shrinkage, PFS 7.5 months; pt 3, 45 mg doublet, 39% tumor shrinkage, PFS censored at 5.5 months) and 1 had gallbladder cancer (45 mg doublet, 50% tumor shrinkage, PFS 7.9 months). A further 7 pts (5 in the monotherapy trial and 2 in the combination trial) achieved stable disease (SD). In both trials, the most common any-grade treatment-related AE (TRAE) was nausea; the most common grade $3 TRAEs were thrombocytopenia and neutropenia.

Conclusions: Brigimadlin showed a manageable safety profile and encouraging preliminary efficacy in pts with BTC, with 7 PRs and 7 SDs in 16 pts. A Phase IIa/IIb trial of brigimadlin in patients with MDM2-amplified, TP53 wild-type BTC and other solid tumors is ongoing (Brightline-2). Clinical trial information: NCT03449381 and NCT03964233. Research Sponsor: Boehringer Ingelheim.

A single-arm, multi-center phase II study of tislelizumab combined with lenvatinib and GEMOX as conversion therapy in potentially resectable locally advanced biliary tract cancer (ZSAB-TransGOLP): A primary analysis. First Author: Jia Fan, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China Background: We have previously reported that GEMOX combined with lenvatinib and PD-1 antibody (GOLP regimen) showed promising efficacy as first-line treatment for advanced intrahepatic cholangiocarcinoma (iCCA), indicating that GOLP regimen may be an ideal conversion therapy for patients (pts) with potentially resectable advanced biliary tract cancer (BTC). This phase II trial explored the efficacy and safety of GOLP as conversion therapy in potentially resectable and locally advanced BTC. Methods: Patients with potentially resectable locally advanced BTC were enrolled and received tislelizumab (200mg, Q3W) and lenvatinib (8mg, QD) and GEMOX chemotherapy (Q3W) including gemcitabine 1000mg/m 2 on day 1, 8 and oxaliplatin 85mg/m 2 on day 1. Tumor responses were evaluated every 9 weeks according to RECIST v1.1, and the resectability was simultaneously discussed by MDT. For pts who were eligible for surgery, capecitabine alone was administered as adjuvant therapy after radical surgery. Pts who was not suitable for surgery continued to the original treatment regimen until progression or intolerable toxicity. n=6 ), and the most common TRAEs (incidence$5%) among them were rash (20.0%), AST elevation (6.7%), fever (6.7%), platelet count decreased (6.7%), fatigue (6.7%), pneumonitis (6.7%).

The combination of sintilimab, bevacizumab and AG chemotherapy was tolerable and showed a promising ORR in initially unresectable GBC patients. This regimen could be a feasible and safe option for initially unresectable GBC, but this needs further validation. Clinical trial information: NCT05757336. Research Sponsor: None.

490 Poster Session

Therapeutic effectiveness of high-intensity focused ultrasound (HIFU) ablation in patients with unresectable hepatocellular carcinoma. First Author: Jin Il Kim, The Catholic University, Seoul, South Korea Background: High-intensity focused ultrasound (HIFU) ablation is a new therapeutic method for treatment of solid tumor. To determine the efficacy and safety of HIFU, we report our experience for local therapy of primary or metastatic hepatocellular carcinoma (HCC). Methods: From January 2015 to December 2022, forty-eight patients with unresectable HCC underwent single or two therapeutic sessions of HIFU under general anesthesia. Ten patients with liver metastasis from colon cancer and three patients with liver metastasis from stomach cancer were included. We used HIFU, ultrasound-guided extracorporeal system (HIFU Technology Company, Chongqing, China). Thirty-three patients received transarterial embolization before HIFU. Thirteen patients were treated with chemotherapy before HIFU. Technical effectiveness per patient and per masses was assessed according to clinical findings and MR imaging at follow-up. Complications were also recorded. Results: We treated total 78 tumors in 48 patients. The tumor size ranged from 1.3 cm to 12 cm in diameter. Small (, 3 cm), intermediate (3-5 cm) and large tumors (.5 cm) are 44, 24 and 10 patients, respectively. Average procedure time was 4 hours 10 minutes with 68 minutes treatment time. We made the artificial pleural effusion to get treatment field in 25 patients. Mean follow-up period was 52 weeks. For the technical effectiveness per patient as follows: complete ablation with no evidence of recurrence on follow up in 18%, apparent complete ablation of target mass with progression of new lesions on follow up in 29%, recurrence after apparent complete ablation in 26%, and incomplete ablation at 2 week follow up in 27%. Average postprocedure hospital day was 5.4 days. No severe complication except mild right upper quadrant pain was observed after treatment. Conclusions: HIFU is an effective and safe treatment option for local image-guided tumor ablation in patients with unresectable HCC. Although further study is necessary, these results show that HIFU may be helpful in treating unresectable HCC. Research Sponsor: None.

491 Poster Session

Understanding the efficacy of frontline therapies for hepatocellular carcinoma through etiologic stratification. First Author: Maksym Goryachok, University of Colorado School of Medicine, Aurora, CO Background: Despite significant advancements in recent years, hepatocellular carcinoma (HCC) treatment options remain limited for patients who progress on locoregional therapy. Given increasing interest in personalized cancer care for HCC, analysis was done to understand whether the etiology of HCC influenced the efficacy of four common first-line FDA approved systemic therapy regimens. Methods: This study used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database from 1/1/2003 to 8/1/2021 with 3519 HCC patients who have received either atezolizumab-bevacizumab (AB), nivolumab, sorafenib, or lenvatinib as a first-line systemic therapy. Information on demographics (age, gender, sex race, ethnicity, ECOG, SES Index), cancer stage, and treatment type was collected. In addition, comorbidities of hepatitis B, hepatitis C, alcohol use, diabetes, and obesity were collected as surrogates for disease etiology: viral hepatic disease, alcohol induced hepatic dysfunction or non-alcoholic fatty liver disease (NAFLD). Patients with missing data in any of the population stratifying variables were excluded. Overall survival (OS), Progression-free-survival (PFS) and time to treatment discontinuation (TTTD) were analyzed for each systemic therapy stratified by etiology as endpoints. Kaplan-Meier (KM) univariate analysis was performed along with the log-rank test for the primary outcome. Multivariate analysis (MVA) was conducted on all three endpoints via cox proportional hazard model to adjust for possible covariates in the patient population.

Results: After exclusion criteria, 548 patients with complete data were included (AB N=124, Sorafenib N=324, Lenvatinib N=61, Nivolumab N=39) with variable etiologic presence (hepatitis B N=14, hepatitis C N=50, alcohol use N=41, diabetes N=50, Obesity N=44). When comparing patients across all recorded systemic therapies stratified by the etiologic variables, there was no statistically significant difference in OS, PFS, or TTTD. When stratified by presence of Hepatitis B, patients treated with atezolizumabbevacizumab trended towards improved outcomes but did not reach statistical significance (P = 0.064). Other treatments showed mixed results in relation to specific etiologies, but no clear trend in efficacy emerged. Conclusions: This early retrospective study suggests that systemic therapy for HCC is not significantly impacted by factors associated with the etiology of disease, such as hepatitis C, alcohol use, and obesity. However, small population sizes and potential nonrandom covariate missingness in this study may obscure effects. Future studies are needed to further elucidate this trend along with subpopulation effects of other systemic therapies. Research Sponsor: None.

Characterizing outcomes of ERBB2-amplified biliary tract cancer. First Author: Daniel Aaron Fox, Baylor College of Medicine, Houston, TX

494 Poster Session

Preliminary results of ALTER-H006: A phase II study of TQB2450 plus anlotinib as adjuvant therapy in hepatocellular carcinoma (HCC) with high risk of recurrence after radical resection. First Author: Xianhai Mao, Hunan Provincial People's Hospital, Changsha, China Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancerrelated death. Surgical resection remains as the mainstay of curative treatment option, However, the recurrence rate after surgical resection could be high especially in patients with CNLC stage IIb (tumor number $ 4) and IIIa (vascular invasion). Herein we evaluated the efficacy and safety of the anti-angiogenic tyrosine kinase inhibitor, anlotinib, plus TQB2450, a novel programmed death-ligand 1 (PD-L1) inhibitor as an adjuvant treatment for HCC with high risk of recurrence after radical resection.

495 Poster Session

Phase II study of atezolizumab and bevacizumab combination therapy for patients with advanced hepatocellular carcinoma who previously received systemic treatment. First Author: Takeshi Terashima, Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan Background: Atezolizumab plus bevacizumab (AteBev) has been established as a standard of care for patients with untreated advanced hepatocellular carcinoma (HCC).

Lenvatinib was once the first choice and remains a treatment option for such patients; however, no subsequent treatment to date has proven a similar level of efficacy. This study aimed to evaluate the efficacy of AteBev in patients with HCC previously treated with lenvatinib. Methods: In this single-center, open-labeled, single-arm, phase II study, patients with advanced HCC previously treated with at least one systemic treatment were enrolled to receive 1,200 mg of atezolizumab and 15 mg/kg of bevacizumab intravenously every 3 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rate, tumor control rate, and frequency of adverse events. The threshold and expected PFS were 3 months and 6.8 months, respectively, at a one-sided significance level of 0.05, and statistical power of 80%. Based on these data, the number of patients required was estimated to be 26. Results: Among 29 patients enrolled between November 2020 and October 2022, 26 previously treated with lenvatinib were included in the primary efficacy analysis. Median PFS was 9.70 [90% confidence interval (CI), 5.10-14.24] months. Median overall survival was 17.23 (90% CI, ) months, and response rate and tumor control rate were 34.6% and 69.2%, respectively. Severe adverse events were observed in six patients (23.1%), six patients (23.1%) discontinued treatment because of immune-related adverse events or treatment-refractory ascites, and 10 patients (38.5%) required the withdrawal of treatment mainly because of proteinuria. There were no treatment-related deaths. Conclusions: AteBev for patients with advanced HCC previously treated with lenvatinib had a comparable efficacy to that in patients with no prior treatment. It may therefore be a treatment option for patients with advanced HCC previously treated with lenvatinib. Clinical trial information: jRCT1041200068. Research Sponsor: None.

Lenvatinib plus hepatic arterial infusion chemotherapy with cisplatin for advanced hepatocellular carcinoma. First Author: Makoto Yamamoto, Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan Background: A recent phase II study demonstrated that combination therapy with lenvatinib and hepatic arterial infusion chemotherapy using cisplatin (Lenva+CDDP) had high anti-tumor effects for patients with advanced hepatocellular carcinoma (HCC) with no prior history of systemic chemotherapy; however, whether the efficacy of Len-va+CDDP is superior to lenvatinib monotherapy remains unclear. Methods: We retrospectively reviewed the medical records of patients with advanced HCC and a Child-Pugh score of 5, 6, or 7 who were treated with Lenva+CDDP or lenvatinib, and compared the efficacy between the treatments. Patients in both groups received a once daily dose of lenvatinib (8 mg or 12 mg according to their weight), and the Lenva+CDDP group also received 65 mg/m 2 of CDDP via the hepatic artery every 4 weeks. Background: Efficacy and prognosis of chemotherapy in first-line setting for patients with advanced biliary tract cancer (BTC) was dismal currently. Recently, PD-1/PD-L1 blockades combined with dual chemotherapy in first-line setting exhibited superior efficacy for patients with BTC. Nevertheless, it's important to highlight that both the TOPAZ-1 and KEYNOTE-966 trials had reported a median OS of less than 13 months. This underscored the necessity for further advancements to meet the demands of clinical practice. Anlotinib, a novel multitarget TKI primarily targeting VEGFR1-3, demonstrated promising therapeutic activity as second-line therapy for patients with BTC. Therefore, this study was designed to explore the efficacy and safety of anlotinib plus TQB2450 (PD-L1 blockade) combined with nab-paclitaxel and cisplatin as first-line therapy in advanced BTC. Methods: Patients with previously untreated metastatic or locally advanced BTC (ICC, ECC, GBC) were recruited and treated with anlotinib (10mg, po, d1~14, q3w) and TQB2450 (1200mg, iv, d1, q3w) plus nab-paclitaxel (200mg/m 2 , iv, d1, q3w) and cisplatin (60mg/m 2 , iv, d1, q3w) until disease progression or unacceptable toxicity. The tumor response was assessed according to RECIST 1.1 using CT scans every two cycles. Adverse events were recorded by severity in accordance with the NCI CTC AE Version 5.0. The predefined sample size was 20. Primary endpoint was ORR and secondary endpoints included safety, DCR, PFS, OS and biomarker explore.

Results: From April 2023 to Aug 2023, a total of 18 patients were enrolled, 14 patients who had received first tumor response were included in this analysis. The best overall response indicated that there were 6 PR (42.9%), 7 SD (50.0%) and 1 PD (7.1%). Therefore, the preliminary ORR was 42.8% (95%CI: 17.7%-71.1%), DCR was 92.9% (95% CI: 66.1%-99.8%). Median PFS of the 14 patients was not yet reached. Additionally, safety profile exhibited that the regimen was tolerable. The most common treatmentemergent adverse events among the 18 patients with the incidence .30% were leukopenia (67%), fever (39%), pain in extremity (33%) and malaise (28%). Common grade $3 treatment-emergent adverse events were leukopenia (28%), fever (6%), malaise (6%), stomachache (6%), oral mucositis (6%), thrombocytopenia (6%), vomit (6%), rash (6%) and hypotension (6%). Conclusions: Preliminary results suggested that anlotinib plus TQB2450 combined with nab-paclitaxel and cisplatin as first-line therapy in advanced BTC exhibited encouraging efficacy and manageable adverse events. The conclusion should be validated in more patients consecutively. Clinical trial information: NCT05812430. Research Sponsor: None.

499 Poster Session

Fruquintinib combined with sintilimab plus transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma Median PFS (months, 95%CI)

2.5 (1.9-3.8) 2.1 (1.1-1.3) 2.5 (1.9-3.8) NR 2.5 (1.9-3.8) 1.6 (1.0-3.0) 2.6 (1.4-3.2) ORR (%,95%CI) (N=43)

16.3 (6.5-33. 7 . 4 (0.9-26.7) 5.5 (0.1-30.9) 37.5 (7.7-100)

503

Perioperative lenvatinib combined with tislelizumab plus transcatheter arterial chemoembolization in resectable hepatocellular carcinoma with highrisk of recurrence: A prospective, single-arm, phase 2 trial. First Author: Jia-Yi Wu, Fujian Provincial Hospital, Fuzhou, China Background: Early recurrence is common after surgery for hepatocellular carcinoma (HCC) and associated with poor prognosis. There is no standard of care neoadjuvant therapy. The combinations of lenvatinib, anti-PD-1 antibodies and transcatheter arterial chemoembolization (TACE) (triple therapy) has shown better trend in tumor response and survival outcomes on unresectable HCC. This study aims to explore the efficacy and safety of triple therapy in the neoadjuvant therapy of resectable HCC patients with highrisk of recurrence. Methods: This prospective, single-arm, phase 2 trial (ChiCTR2100048249) enrolled patients with primary resectable HCC who had not received prior anti-tumor therapy. TACE will be performed once on Day 1. Tislelizumab (an anti-PD-1 antibody, 200 mg) intravenously once every 3 weeks and lenvatinib (bodyweight $ 60 kg, 12 mg; , 60 kg, 8 mg) orally daily was initiated within 7-10 days after TACE treatment. Surgery was performed 8 weeks after treatment. After 4-8 weeks of surgery, patients continued to receive tislelizumab and lenvatinib for 6 months.

Primary endpoint was relapse-free survival (RFS

504 Poster Session

The interim analysis of a single-arm, open-label, phase II study investigating ALLEN regimen (durvalumab plus albumin paclitaxel and lenvatinib) in patients with unresectable biliary tract cancers (BTCs). First Author: Zhifang Li, Department of Bio-therapeutic, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China

Background: BTCs are a heterogeneous group of malignancies with a poor prognosis. Despite the improved outcome achieved by the addition of the anti-PD-L1 antibody durvalumab to standard chemotherapy, the benefits were modest and cannot satisfy the clinical demands adequately. This study aimed to evaluate the efficacy and safety of the combination therapy of Albumin paclitaxel, Durvalumab and Lenvatinib (ALLEN regimen) in unresectable BTCs. Methods: This single-arm, single-center, open-label, phase I/Ⅱ study enrolled patients with locally advanced or metastatic BTCs. Eligible patients with ECOG score 0-2 were treated with ALLEN regimen. Durvalumab (1000mg IV, q3w) in combination with albumin paclitaxel (180-220 mg/m 2 IV q3w) and lenvatinib (8mg PO QD) were given regularly until disease progression. The primary endpoint was objective response rate (ORR) evaluated by investigators according to RECIST 1.1. The secondary endpoints were disease control rate (DCR), progression-free survival (PFS) and treatment-related adverse events (TRAEs). Results: From September 2021 to September 2023, fourteen patients were enrolled including three patients who were failed to prior anti-PD-1 antibody treatment. The median follow-up was 6.8 months (95% CI 1.9, 10.9). The median age of the patients was 59.0 years, and male patients accounted for 35.7%. The ORR and DCR were 35.7% and 100%, respectively. The median PFS was 7.3 months (95% CI 4.9, 8.2). TRAEs of any grade occurred in 13 (92.9%) patients without grade 3 or higher. The most common TRAEs were alopecia (13/14, 92.9%), peripheral sensory neuropathy (10/14, 71.4%), decreased appetite and nausea (9/14, 64.3%), hypertension (6/14, 42.9%), rash (5/14, 35.7%), diarrhoea (4/14, 28.6%), and asthenia (4/ 14, 28.6%). Conclusions: The ALLEN regimen demonstrated encouraging anti-tumor activity with a tolerable safety profile in unresectable BTCs. The preliminary results were promising, which deserved further investigation in a larger population. Clinical trial information: NCT05327582. Research Sponsor: None.

505 Poster Session

Adjuvant TACE plus lenvatinib as compared with TACE alone in patients with hepatocellular carcinoma at high risk of recurrence after surgery: A prospective controlled study. First Author: Bin Zhang, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China Background: Hepatocellular carcinoma (HCC) remains the fourth leading cause of cancer related deaths globally. Radical resection is still the main curative approach for patients with resectable HCC in China. However, the high 5-year postoperative recurrence rate of about 40% to 70% had become the main negative factor affecting the longterm survival benefit. Although transarterial chemoembolisation (TACE) can effectively reduce the recurrence rate and improve disease-free survival (DFS) and overall survival (OS), the outcomes of patients at high risk of recurrence are still not satisfactory. Thus, there is an urgent need for new adjuvant treatment regimen to further improve the survival outcomes. In this study, we compared the efficacy and safety of the lenvatinib plus TACE with TACE alone for postoperative patients with HCC who were at high risk of recurrence. Methods: The factors associated with high risk of recurrence were defined as pathological suggested vascular invasion (including vascular embolus, cholangiocarcinoma embolus and microvascular invasion), suspicious positive surgical margin or surgical margin , 1cm, satellite lesion with cancer, positive lymph nodes, low differentiation and incomplete envelope. Eligible patients were those who had received radical resection for HCC and had risk factors above. Patients were assigned in a 1:1 ratio to receive the combination of lenvatinib and TACE or TACE alone. Results: From September 2019 to May 2023, 119 patients were enrolled in Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. Sixty received TACE + lenvatinib and 59 received TACE only. The baseline characteristics were similar between two groups. The median duration of follow-up was 22.5 months (rang: 3 to 47) in TACE + lenvatinib group and 23 months (rang: 5 to 48) in TACE group. The 1-year DFS rate was 81.2% (95% CI: 70.8%-93.1%) in lenvatinib + TACE group, which was significantly higher than that of TACE group (58.3% [95% CI: 46.8%-72.7%], p = 0.0087; HR = 0.44 [95% CI: 0.23-0.83]). The median DFS was not reached (95% CI: 28-NR) in lenvatinib + TACE group, and was 20.0 months (95% CI: 12.0-NR) in TACE group. Patients' liver function after treatment with TACE + lenvatinib was comparable to that in the baseline. Conclusions: The preliminary results of this study suggested that adjuvant lenvatinib in combination with TACE can significantly improve DFS compared with TACE alone in patients with HCC at high risk of recurrence after surgery. The toxicity of combined treatment was tolerable and manageable. The follow up is still ongoing to observe the long-term benefit of this treatment regimen. Research Sponsor: None.

Qualification of major pathological response as a surrogate endpoint for relapse-free survival following neoadjuvant immunotherapy for hepatocellular carcinoma. First Author: Antonio D'Alessio, Imperial College, London, United Kingdom

Background: Neoadjuvant use of immune checkpoint inhibitors (ICI) is feasible and achieves pathological responses in a subset of patients with hepatocellular carcinoma (HCC). However, it is not clear whether pathological response to ICI translates into longterm survival benefit. Methods: We analysed patient-level data from 86 subjects recruited to 4 prospective phase I/II clinical trials of ICI prior to liver resection (LR) in 9 centres in the United States, Europe, and Asia and included a cohort of 23 patients (pts) receiving neoadjuvant ICI off trial. Radiological response was assessed with RECISTv1.1. Major (MPR) and complete pathological response (pCR) were considered as $70% and 100% non-viable tumour in the resected specimen, respectively. Pathological responses were correlated with radiologic overall response rates (ORR) and relapse-free survival (RFS). Results: Out of 109 pts treated between 10/2017 and 09/2023, 55 pts (50.5%) received a double ICI combination, 35 (32.1%) ICI monotherapy, and 19 (17.4%) an antiangiogenic/ICI combination. In 19 pts (17.4%) an adjuvant ICI course was administered for a median time of 5.5 months (m) (interquartile range [IQR] 3.7-6.0). Most of pts were male (77.6%) with underlying viral chronic liver disease (68.2%), performance status 0 (83.5%), BCLC 0-A (55%), a median tumour diameter of 6.0 cm (IQR 3.9-9.9) without portal vein thrombosis (75.7%). After a median follow-up of 27.3 m (95% CI 21.5-33.0), 35 (32.1%) relapses and 14 (12.8%) deaths occurred. Radiologic ORR was 28.5% (n=31), with 3.7% complete responses (CR, n=4) and 24.8% partial responses (PR, n=27).

526

Poster Session Number of subsequent treatments and time to recurrence in hepatocellular carcinoma. First Author: Juan Jose Juarez, Beth Israel Deaconess Medical Center, Boston, MA Background: Hepatocellular carcinoma (HCC) is often managed with locoregional therapies including surgical resection, ablation, transcatheter arterial chemoembolization (TACE), and selective internal radiation therapy (Y90). Most patients require multiple treatments over several years due to ongoing development of new lesions, distinct from other cancer types. Our project aims to analyze this treatment trajectory and the impact of treatment selection. Here we present an interim analysis focusing on the number of subsequent therapies and time to first recurrence (TTR). Methods: We identified 202 patients newly diagnosed with HCC between 2019-2021 who were seen in the BIDMC Liver Tumor Multidisciplinary Clinic. Complete abstraction of medical records was performed in 51 patients to date. Our primary outcome was of the number of subsequent therapies depending on the selected first-line locoregional therapy. Incidence risk ratios (IRR) were obtained via a crude and adjusted (age, gender, race, Child Pugh) linear regression model. Ablation was used as the reference treatment. Secondary outcomes included survival analysis of TTR, overall survival (OS) and time to initiation of systemic therapy. TTR was defined as the appearance of new lesions, excluding residual disease. Results: Mean age at diagnosis was 65 years old, 73% were male, and 92% ECOG 0. 37 patients out of 50 had recurrence, almost all local (97%). The total number of subsequent therapies received was 110; the most common treatment received on first recurrence was ablation (59%) followed by Y90 (24%). Patients who received TACE were more likely to undergo a higher number of subsequent therapies in both the unadjusted (IRR 2.51, p,0.001, 95%CI 1.6-3.9) and adjusted analysis (IRR 4.43 p,0.001, 95%CI 2.5-8.1) with 4.4 (2-9) mean subsequent treatments when compared to ablation with a mean number of subsequent treatments of 1.47 (0-7). Y90 had 1.85 (0-7) mean subsequent treatments and surgery 1.87 (0-7), with inconclusive results regarding IRR when compared to ablation. Median TTR was 19.1 months (10.2-29.3) with ablation having the longest time with 22.2 months (13.2-31.1), followed by surgery with 20.3 months (13.3-29.3), Y90 with 19.1 months (6-NR) and TACE with 12.1 (6.1-21.2). Median OS was not reached, and only 5 patients started systemic therapy. Conclusions: This interim analysis shows that patients treated with TACE as the first locoregional therapy are likely to undergo a higher number of subsequent treatments when compared to ablation.

527 Poster Session

Histopathologic and genomic profile characteristics of biliary cancers related to pancreaticobiliary maljunction. First Author: Shodai Tohyama, Chiba University Hospital, Chiba, Japan

Background: Pancreaticobiliary maljunction (PBM) is a congenital malformation in which the pancreatic duct and bile duct anatomically merge outside the duodenal wall, and is associated with a high rate of biliary cancer. It has been reported that TP53 and KRAS mutations are found not only in the cancerous area but also in the noncancerous area. However, there is no report of precise mapping of genetic mutations throughout the gallbladder and bile ducts. Methods: Ninety-seven patients (including 31 patients with biliary cancer) who underwent cholecystectomy and cholangiectomy for PBM between 1990 and 2023 at our hospital and affiliated hospitals were included in the study, and consent forms were obtained from 36 patients. The panel targeting 60 genes frequently identified in biliary tract cancer was created in-house and deep sequenced to compare with clinicopathological features. To date, we have analyzed 4 patients with biliary tract cancer and 5 patients without it (with prophylactic resection). The same analysis was also performed on cancerous and noncancerous parts of patients of gallbladder cancer and cholangiocarcinoma without confluence abnormalities for comparison. Results: A total of 33 Samples (7 cancerous parts and 26 noncancerous parts) were examined for biliary tract cancer. We found a variety of functional gene abnormalities, including driver mutations such as TP53, ARID2, and BRCA2, in 9 noncancerous areas including hyperplasia and normal bile duct mucosa. Some of these mutations were not shared with cancerous areas. On the other hand, in 46 samples from 5 patients who did not develop gallbladder cancer (prophylactic resection), Driver mutations were found in only 3 sites. Pathological findings of dysplasia/hyperplasia in these prophylactic resections were observed in 28 of the 46 sections. In addition, Driver mutations were rarely observed in noncancerous areas in patients with normal gallbladder or cholangiocarcinoma. Conclusions: Unlike conventional biliary tract cancers, the patients with PBM showed a great variety of genetic abnormalities in both cancerous and noncancerous areas. On the other hand, in patients of prophylactic resection without cancer, driver mutations were almost completely absent despite the presence of mucosal changes. We believe that these findings can develop better strategy for biliary cancers with PBM. Research Sponsor: None.

528 Poster Session

The role of pre-operative ctDNA in resectable intrahepatic cholangiocarcinoma. First Author: Woo Jin Choi, University of Toronto, Toronto, ON, Canada

Background: Genomic profiling of circulating tumor DNA (ctDNA) is increasingly used in intrahepatic cholangiocarcinoma (iCCA) to inform precision oncology approaches and determine resistance mechanisms to targeted therapies. The application of pre-operative ctDNA testing in the management of iCCA for prognostication remains unclear. Methods: In this retrospective study, we analyzed preoperative plasma samples from 14 patients who underwent curative resection for iCCA without neoadjuvant therapy. A personalized and tumor-informed assay (Signatera; Natera, Inc.) was used for the detection and quantification of ctDNA. We correlated ctDNA profiles with baseline tumour characteristics and clinical outcomes. Results: The mean interval between pre-operative blood collection and surgery was 43 days (range: 1 to 90 days). ctDNA was detected in all patients except for one with stage Ia (AJCC 8th) disease (Table ). The mean pre-operative ctDNA concentration was lowest in the stage Ia group [4.2 mean tumor molecules (MTM)/mL] and highest in the stage II group (134.0 MTM/mL). The mean pre-operative ctDNA concentration did not exhibit a linear correlation with disease recurrence or mortality rates, however, it showed a moderate-to-good linear correlation with the largest pathologic tumor size (R 2 = 0.55). Among the three patients who had IDH1/2 mutations tracked in the plasma by Signatera, two patients had positive IDH1/2 detection in ctDNA with mean ctDNA concentrations of 83.7 MTM/mL (range: 33.8 to 133.5 MTM/mL). The patient with the secondhighest ctDNA concentration (133.5 MTM/mL and 1818 days follow-up) had stage Ib disease with an IDH1 mutation but has shown no evidence of recurrence. Conclusions: In the pre-operative setting for iCCA resections, ctDNA can be reliably detected across all disease stages using a tumor-informed approach, even when blood is collected up to 90 days before surgery. While single time-point preoperative ctDNA concentration levels do not appear to correlate with outcomes, similar to previous reports in colon adenocarcinoma, they may correlate with tumor volume. Further studies are needed to evaluate the utility of tumor-informed ctDNA testing in the post-operative setting to detect molecular residual disease for improved prognostication. Research Sponsor: Natera.

ctDNA measurement in the context of iCCA tumor burden and clinical outcomes. Visit meetings.asco.org and search by abstract for the full list of abstract authors and their disclosure information.

Stages

Cost-utility analysis of sequential therapy with sorafenib followed by regorafenib versus single-line therapies in advanced hepatocellular carcinoma.

First Author: Jamie Grossman, Bayer, Columbus, OH Background: Regorafenib is the only licensed second-line therapy available for patients with advanced hepatocellular carcinoma (HCC) that progress on first-line sorafenib in the UK. We evaluated the lifetime cost-effectiveness of a sequence of treatment with sorafenib followed by regorafenib (SOR-REG) compared with licensed single-line therapies for which there is no clear sequencing options available, including atezolizumab plus bevacizumab (ATEZO+BEV), which has become the standard of care in firstline treatment, as well as lenvatinib (LEN), followed by best supportive care (BSC). Methods: Assuming a UK National Health Service and Social Services perspective, we developed a probabilistic individual-level semi-Markov model with states reflecting progression-free survival, progression following first-line treatment, further progression following second-line treatment, and death. First-line overall survival (OS) and progression free survival (PFS) were informed by fractional polynomials network metaanalysis of published trials. Individual patient data from a phase 3 trial (RESORCE) on regorafenib and BSC informed OS and PFS in the second-line setting. Costs and utilities were sourced from published studies. Cost-effectiveness was summarized using incremental net monetary benefit (INMB), which could be positive or negative depending on direction of expected benefit associated with SOR-REG, and cost-effectiveness acceptability curves at willingness-to-pay (WTP) thresholds. Results: We found 1000 probabilistic samples and 1000 patients were sufficient for convergence.

530 Poster Session

Prognostic value of minimal residual disease profiling in resectable hepatocellular carcinoma. First Author: Jie Hu, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China Background: Detecting post-surgical residual disease is a critical clinical requirement in resectable hepatocellular carcinoma (HCC). Previous studies focused on specific genomic regions have indicated that ctDNA holds promise as a tool for prognostic assessment. Nevertheless, these methods exhibited limited sensitivity and failed to meet the minimal residual disease (MRD) threshold. Here we report the prognostic value of MRD profiling in HCC patients who have undergone hepatectomy. Methods: This retrospective study involved 88 HCC patients who underwent surgical resections in China, from January to May in 2016. During surgery, tumor and normal tissue specimens were collected. Plasma samples were obtained 7 days post-surgery. PredicineBEACON, a baseline tissue-or blood-informed MRD assay, was used for MRD profiling. This entailed identifying tumor-specific mutations through whole exon sequencing of tissue samples. Subsequently, a personalized MRD panel, selecting up to 50 mutations via bioinformatics pipelines merged with a fixed panel featuring 500 tumor actionable hotspots, was created for each patient. To detect MRD in post-surgery plasma samples, we employed ultra-deep sequencing at a coverage of 100,000X, utilizing the designed panel.

Results: In the cohort of 88 patients, the distribution based on Barcelona Clinic Liver Cancer (BCLC) staging was as follows: 79.5% stage A (N=70), 12.5% stage B (N=11), and 8.0% stage C (N=7,). The MRD assay identified 36 patients as MRD+ and 52 patients as MRD-. We observed significant correlations between MRD status and both relapse-free survival (RFS) and overall survival (OS). For MRD+ patients, the median RFS was 17.1 months, while it was not reached for MRD-patients (p=0.0013). Likewise, the median OS for MRD+ patients was 40.1 months, in contrast to it not being reached for MRD-patients (p=0.0012). The MRD positivity rate stood at 100% in stage C patients, a significantly higher percentage compared to the rates observed in stage B (36.4%, p=0.0256) and stage A (36.2%, p=0.0042). Significantly, MRD status emerged as a pivotal prognostic differentiator among clinically low-risk patients in stage A: among MRD+ patients, the median RFS was 23.3 months, whereas it was not reached for MRDpatients (p=0.05). Additionally, the median OS of both MRD+ and MRD-was not reached but their survival curves showed significant differences (p=0.038). Conclusions: This study demonstrated the clinical utility of ctDNA MRD assay in patients with resectable HCC, as notably evident in the robust detection of MRD using plasma samples collected 7 days after surgery. Furthermore, the assessment of post-surgical MRD status provided valuable prognostic insights into both patient survival and the risk of disease relapse. ctDNA MRD status played a pivotal role as a prognostic differentiator, particularly among clinically low-risk patients. Research Sponsor: None.

531 Poster Session

Genomic characterization of cholangiocarcinoma with autoimmune etiologies. First Author: Xin Wang, Princess Margaret Cancer Centre, Toronto, ON, Canada

Background: Chronic inflammation from autoimmune conditions is a well-recognized risk factor for cholangiocarcinoma in the Western world. Cholangiocarcinomas in the setting of autoimmune disease have earlier age-of-onset and worse prognosis. Currently, their biology is inadequately understood, and the risks and benefits of immunotherapy approaches in this population are unknown. We describe the clinical and genomic characteristics of a cohort of cholangiocarcinoma patients with autoimmune etiologies. Methods: In a prospective cohort of 43 patients with mismatch repair proficient cholangiocarcinoma, we performed whole-genome sequencing (WGS, n=43) and total RNA sequencing (RNA-seq, n=28). Among this cohort, 15 patients had cholangiocarcinoma with autoimmune etiologies, including primary sclerosing cholangitis (PSC, n=10), ulcerative colitis (UC, n=6), ankylosing spondylitis (AS, n=1), and Crohn's disease (CD, n=3). Results: Patients with autoimmune conditions had a 6.46-fold higher Tumour Mutational Burden (TMB) (P = 0.0010), characterized by higher load of indels (P = 0.0006). TMB was greater than 10 mutations per megabase in 4 of 15 patients with autoimmune conditions and 0 of 28 patients in those without (P = 0.0111). Autoimmune patients exhibited an enrichment in mutational signatures 5 (P = 0.0154), 17 (P = 0.0004), 28 (P = 0.028) and 30 (P = 0.0164). Despite a higher TMB, autoimmune tumours have similar patterns of driver mutations. Differential gene expression of bulk RNA-seq analysis revealed comparable transcriptional markers of immunogenicity, but autoimmune cancers are enriched in pathways involved with cell proliferation and cell-cycle checkpoints. One patient with PSC/UC was treated with gemcitabine, cisplatin, and durvalumab with a partial response, while another with Crohn's disease had durvalumab added to gemcitabine and cisplatin at progression and experienced stable disease with a decreased CA19-9. Neither experienced immune-related adverse events. Conclusions: Cholangiocarcinoma with autoimmune etiologies have unique genomic features characterized by elevated TMB. Chemo-immunotherapy may be a novel therapeutic option in this subgroup of patients and warrants further study. Research Sponsor: Richard LeGresley Biliary Cancer Research Fund at the Princess Margaret Cancer Foundation.

532 Poster Session

Clinical characteristics of patients with advanced hepatocellular carcinoma who received long-term treatment with atezolizumab and bevacizumab for more than one year. First Author: Youngun Kim, CHA University School of Medicine, Seongnam, South Korea Background: Atezolizumab plus bevacizumab (Ate/Bev) has become the standard of care since 2020 as a first-line systemic therapy for unresectable hepatocellular carcinoma (HCC). However, studies on patients receiving long-term treatment with Ate/Bev are still lacking. In this study, we evaluated the clinical characteristics and impacts on patients receiving Ate/Bev treatment for more than one year. Methods: We prospectively enrolled 246 patients with unresectable HCC who received Ate/Bev treatment at three tertiary cancer centers in Korea between May 2020 and April 2022. Comparative analyses were performed between patients treated with Ate/Bev for more than one year and those treated for less than one year. Additionally, treatment-related adverse events (AEs), and changes in liver function were evaluated. Results: Of the 246 patients, 69 (28.0%) were treated with Ate/Bev for more than one year. The long-term treatment group showed better Eastern Cooperative Oncology Group performance status, liver function, and lower residual hepatic tumor burden at baseline, compared to the group treated for less than one year. Furthermore, the long-term treatment group had a higher incidence of atezolizumab-related thyroid dysfunction (30.4% vs. 10.7%, p AE 0.001), dermatologic toxicity (30.4% vs. 14.1%, p = 0.006), and bevacizumab-related hypertension (43.5% vs. 22.6%, p = 0.002) and proteinuria (68.1% vs. 39.0%, p AE 0.001), compared to the less than one-year treatment group. The median time to onset of thyroid dysfunction and dermatologic toxicity after Ate/Bev treatment was 2.8 months and 3.3 months, respectively, while the median time to onset of hypertension and proteinuria was 4.2 months and 6.8 months, respectively. In the long-term treatment group, 30 patients (43.5%) showed an increase in Child-Pugh score, 20 (29.0%) had an increase in Child-Pugh grade during Ate/Bev treatment. Conclusions: The Ate/Bev longterm treatment group had better performance status, liver function, and a lower residual hepatic tumor burden at baseline. Atezolizumab-related immunologic adverse events occurred mostly early in the course of treatment, whereas bevacizumab-related adverse events occurred relatively later. In addition, a fraction of patients experienced deterioration of liver function during long-term Ate/Bev treatment. Research Sponsor: None.

Patient-derived biliary tract cancer organoid biobank: Is personalized medicine utilizing organoids feasible for patients with cholangiocarcinoma? First Author: Naaz Nasar, Memorial Sloan Kettering Cancer Center, New York, NY Background: Cholangiocarcinoma (CC) is an aggressive malignancy with an all stage 5year survival rate of less than 15%. Preclinical research is of pivotal importance to acquire a deeper understanding of CC and improve outcomes. The establishment of CC organoids has previously been described to be difficult due to fewer driver mutations and limitations in the ability to mimic tumor microenvironment. The aim of this study was to develop a successful culturing system for CC organoids that preserves intratumoral heterogeneity, and in turn, to determine the feasibility of personalized medicine in patients with CC using organoids. Methods: From 2020-2023, 75 CC tumor samples were prospectively collected from 65 patients. The tumors were sequenced using MSK-IMPACT, a targeted next generation sequencing (NGS) platform. Samples were processed, and organoids were generated and cultured following a standardized protocol. The organoids were grown in three different types of enriched media (M1, M2, and M3).

Once cultures were adequately expanded, organoid lines were sequenced using MSK-IMPACT and/or MiSeq, a benchtop NGS platform. Mutations of the organoid line were compared to that of the tumor of origin to determine tumor enrichment. To ascertain genotypic association with organoid formation, we examined frequencies of driver mutations of interest. Logistic regression was used to assess the univariate association between mutations of interest and organoid establishment. Two-sided p-values less than 0.05 were considered to be significant. Results: Of the 75 samples collected, 24 (32%) were extrahepatic CC tumors, and the remaining were of intrahepatic origin. 92% of the samples were collected from primary tumors, and 71% of the samples were chemotherapy naïve. 64 samples successfully grew organoids. Upon evaluation of MSK-IMPACT and MiSeq data, 11 of the 64 samples were noted to retain the mutations of the tumor of origin in organoid culture; the overall success rate of tumor organoid formation was 14.6% (11/75). Tumor enrichment of organoid lines was most commonly achieved using M3 (9 out of 11 samples), the median passage at which tumor enrichment occurred was 8 (interquartile range (IQR) 2-10), indicating that the approximate median time to tumor organoid formation was 16 weeks (IQR 4-20 weeks). There was no statistically significant association between driver mutations and organoid establishment. Conclusions: Intratumoral heterogeneity of cholangiocarcinoma is maintained in organoid culture. This preclinical model potentially recapitulates the clinical features of the disease seen in humans. However, prolonged duration and low success rate of tumor enrichment makes it a less appealing avenue for personalized medicine. Research Sponsor: National Institute of Health-National Cancer Institute NIH (U01-CA238444).

534 Poster Session

Molecular predictors of response to first-line systemic therapies in advanced hepatocellular carcinoma. First Author: Jeremy Chang, University of California, San Diego, La Jolla, CA

Background: With numerous advances in systemic therapy for advanced hepatocellular carcinoma (HCC) over the past several years, there are now multiple first-line treatment options which can be considered. These options include combination atezolizumab with bevacizumab (atezo/ bev), programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) targeted agents, and oral multikinase inhibitor monotherapy. However, further guidance is needed to predict which patients will respond to best to each regimen. Methods: We performed a single center, retrospective study to determine the association between responses to first-line therapies in advanced HCC and various molecular alterations. Patients received first-line therapy with either atezo/bev, PD-1/PD-L1 monotherapy, or oral multikinase inhibitor monotherapy with treatment responses determined by imaging. All patients underwent next-generation sequencing (NGS) with testing performed on peripheral blood or tumor tissue. Results: A total of 116 patients with advanced HCC were included in this study. For first-line therapies, 45 (38.8%) patients received atezo/bev, 41 (35.3%) received oral multikinase inhibitor monotherapy, and 30 (25.9%) received PD-1/PD-L1 monotherapy. There was no association between treatment responses and patient ethnicity, age, or underlying cirrhosis etiology for any regimen. However, when analyzing NGS results, atezo/bev recipients with telomerase reverse transcriptase (TERT) promoter alterations had significantly higher rates of disease progression (PD) compared those without TERT promoter alterations (91.7% vs 54.6%, p = 0.03). In addition, in the oral multikinase inhibitor monotherapy group, those with CTNNB1 alterations had significantly greater PD rates compared to patients without these alterations (66.7% vs 31%, p = 0.04). There were no significant correlations between molecular alterations and responses in the PD-1/PD-L1 monotherapy group (Table ). Conclusions: In our study, advanced HCC patients who received first-line systemic therapies were found to have significant correlations between TERT promoter and CTNNB1 alterations and responses to atezo/ bev and oral multikinase inhibitor monotherapy, respectively. Given the widespread use of these regimens in the HCC treatment paradigm, additional studies are needed to confirm these findings and determine their impact on survival outcomes. Research Sponsor: None.

Molecular alterations and responses to first-line systemic therapies.

Atezo

535 Poster Session

Analysis of tumor biomarkers in patients (pts) with advanced hepatocellular carcinoma (HCC) from a phase 1b study of E7386, a CREB-binding protein/ b-catenin interaction inhibitor, in combination with lenvatinib. First Author: Masatoshi Kudo, Kindai University, Osaka-Sayama, Japan

Background: E7386, a novel oral anticancer agent, inhibits b-catenin binding to its transcriptional co-activator CREB-binding protein, thus modulating Wnt/b-catenin signaling.

Lenvatinib is a multikinase inhibitor that targets VEGFR 1-3, FGFR 1-4, PDGFRa, RET, and KIT. We previously reported the safety/tolerability, pharmacokinetics, biomarkers, and preliminary efficacy of E7386 plus lenvatinib in 25 pts with HCC in the dose escalation part of a phase 1b study 1 (NCT04008797). Here, we present the results of exploratory tumor biomarker analyses from this study. Methods: Pts with HCC were treated with E7386 10-80 mg QD and 60-120 mg BID plus lenvatinib (bodyweight , 60 kg: 8 mg QD; $ 60 kg: 12 mg QD). Archival or fresh tumor samples were collected at baseline and post-treatment; tumor tissue was assessed for genetic alteration, immunohistochemistry (IHC), and gene expression. Gene signature scores of interest were calculated using obtained gene expression data. The preliminary association between biomarker status and efficacy was investigated. Results: Of the 25 pts enrolled, 22 had baseline tumor samples available for the gene mutation analysis. TERT (6 pts: 27%), CTNNB1 (5 pts: 23%), and TP53 (4 pts: 18%) mutations were detected.

CTNNB1 mutation was confirmed in 3 of 7 responders and 2 of 13 non-responders. Nuclear b-catenin expression was confirmed by IHC analysis in 5 of 16 pts; it was expressed in 3 of 5 pts with CTNNB1 MUT and 2 of 11 pts with CTNNB1 WT. Pts with expression of nuclear b-catenin had 2 partial responses (PRs) among 5 pts; those without b-catenin expression had 2 PRs among 11 pts. Additionally, IHC analysis of tumor microvessel density (MVD; number of CD31 + vessels) at baseline suggested that greater maximum tumor shrinkage (MTS) tended to be observed in the MVD-high population compared to the MVD-low population. 7 Pts had evaluable baseline and post-baseline tumor samples and were included in the gene signature analysis. Despite the small sample size, preliminary results indicated that MTS may be associated with a decrease in Wnt signaling and angiogenesis gene signature scores (spearman r [r]=0.61 for both) and attenuation of hypoxic induction and glycolysis gene signature scores (r=0.79 and 0.68, respectively). Conclusions: These exploratory tumor biomarker analyses suggest that E7386 in combination with lenvatinib may affect the tumor microenvironment in HCC pts through effects on Wnt signaling, angiogenesis, hypoxic response, and glycolysis pathways. This concept is the basis for treatment with this combination. However, given the small sample size, further investigation is needed to confirm these effects on the tumor microenvironment.

536 Poster Session

Molecular differences with therapeutic implications in early-onset compared to average-onset cholangiocarcinoma. First Author: Thejus Jayakrishnan, Taussig Cancer Institute, Cleveland, OH Background: Early-onset cholangiocarcinoma (eoCCA) is among early-onset cancers with the fastest rising rates, yet little is known about its biology. We sought to compare the molecular characteristics of eoCCA with average-onset CCA (aoCCA) with an age cut-off of 50 years, utilizing a real-world multiomics dataset. Methods: The study comprised patients whose tumors underwent molecular analysis at Caris Life Sciences (Phoenix, AZ) using whole exome and whole transcriptome analyses. Patients were categorized by age as eoCCA defined as ,50 years and aoCCA .50 years. Gene expression profiles were analyzed for transcriptional signatures predictive of immunotherapy response including the T-cell inflamed score (TIS) and interferon-gamma (IFG) score. P values (adjusted for multiple testing) were considered significant at False Discovery Rate (FDR)P,0.05 for molecular comparisons and FDR P,0.25 for Gene Set Enrichment Analysis (GSEA). Insurance claims data was used for survival comparison using Kaplan-Meier estimates. Results: The study included 5587 patients -453 patients with eoCCA and 5134 with aoCCA (Table ). Of targetable mutations (FGFR2, IDH1, IDH2, ERBB2, BRCA, BRAF), FGFR2 fusion was significantly more prevalent in eoCCA (15.7% vs 5.9% in aoCCA, FDR P,0.001). Rates trended higher in eoCCAfor MSI-H tumors (4.1% vs 2.4%), and high tumor mutational burden (6.1% vs 5.1%) but not significantly different (FDR P=1). The IFG score (Fold Change FC: 1.1, FDR P=0.01) and TIS (FC:17.3, FDR P=0.03) were significantly higher in aoCCA vs eoCCA. On GSEA, angiogenesis was enriched in eoCCA (normalized enrichment score NES=1.51, FDR P=0.16) while IFG (NES= -1.58, FDR P =0.06) and inflammatory response (NES= -1.46, FDR P=0.18) were enriched in aoCCA. Median OS was longer in eoCCA (16.5 vs 13.3 months, Hazard Ratio (HR) 0.86, 95%CI 0.78-0.95, P=0.004). Among patients treated with immunotherapy, median OS was longer in patients with eoCCA (19.2 months, n=19) vs aoCCA (7.6 months, n=150) -HR 0.52, 95%CI 0.28-0.94, p=0.03. No survival difference was identified in patients on chemotherapy (HR 0.91, 95%CI 0.76-1.08, P=0.28).

Conclusions: In the largest age-stratified analysis of molecular characteristics of CCA, we identified crucial differences, including higher prevalence of FGFR2 fusions and significant differences in immunotherapy-related markers, angiogenesis enrichment, and inflammatory response. Patients with eoCCA experienced better outcomes with immunotherapy even though immune-oncology-relevant markers favored aoCCA. Our findings, especially higher FGFR2 fusion prevalence in eoCCA, underscore the need for NGS testing and the potential for age-tailored therapeutic strategies. Research Sponsor: None. Here, we reviewed the frequency of FGFR2 structural alterations in 8,898 iCCA patients from the AACR Genie and the Foundation Medicine databases. Methods: We reviewed the Foundation Medicine (n= 7,934) and AACR GENIE database (n=964) for intrahepatic cholangiocarcinomas. We identified iCCAs with FGFR2 structural alterations and mutations in other common driver genes and analyzed their distribution by age and sex. Results: FGFR2 structural alterations were more frequent in female (10.4%) compared to male (6.4%) patients across both cohorts. FGFR2 structural alterations had an association with an odds ratio of 2.5 (95% CI 1.6-3.7) and 1.7 (95% CI-2.0) with the female gender in the AACR GENIE and Foundation Medicine databases, respectively. The frequency of FGFR2 fusions/ rearrangement was highest during reproductive years (up to age 40) and subsequently declined with age. This decline was greater in females than males. Mutations in other genes associated with iCCA including non-fusion FGFR2 alterations, and mutations in ARID1A, KRAS, and TP53 were not associated with gender or age. Conclusions: Our results show that FGFR2 structural alterations are significantly enriched in younger female patients with iCCA. Clinical assessment of FGFR2 alterations should be prioritized in this patient population, and future clinical studies in this molecular subtype should ensure inclusive enrollment practices. Further research is warranted to determine if the pathogenesis of FGFR2 structural alterations are driven by female biology including the involvement of sex hormones and the potential impact on the development of acquired resistance to FGFR2 kinase inhibitors. Research Sponsor: None.

538 Poster Session

Prognostic effects of co-occurring TP53 and KRAS aberrations in patients with advanced biliary tract cancer. First Author: Taro Shibuki, Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan

Background: In biliary tract cancer (BTC), TP53 is the most commonly altered gene and may co-occur with KRAS alteration. The presence of a co-alterations in of TP53 and KRAS is associated with poor prognosis in many cancers. In patients (pts) with advanced BTC, the prognostic implications of such co-alterations have not been fully investigated.

Methods: This is a pooled analysis of SCRUM-Japan GOZILA and MONSTAR-SCREEN-1 and -2 studies. Genomic profiling was conducted with Guardant360 for plasma in GOZILA, FoundationOne CDx for tissue and FoundationOne Liquid CDx for plasma in MONSTAR-SCREEN-1, and CARIS MI Profile for tissue in MONSTAR-SCREEN-2. Pts with advanced BTC receiving systemic therapy were included in this study. Results: Among 636 pts with advanced BTC, 85 had TP53/KRAS co-alteration, 293 had TP53, 44 had KRAS, and 214 had neither KRAS nor TP53 alteration (WT/WT). Tumors with TP53 alteration had significantly higher level of tumor mutation burden (TMB) compared to the other groups (3.8 mut/Mb for TP53/KRAS, 5.0 mut/Mb for TP53, 2.8 mut/Mb for KRAS, and 2.5 mut/Mb for WT/WT, respectively, P,0.001). In addition, the frequency of microsatellite instability-high (MSI-High) in the TP53/KRAS group (11.0%) was significantly higher compared to the TP53 group (3.1%, P,0.05), and the WT/WT group (0.6%, P,0.001), respectively. The objective response rate of first-line therapy in the TP53/KRAS group (8.2%) was significantly lower than in the other groups (20.8% for TP53, 23.3% for KRAS, and 19.7% for WT/WT groups, P=0.035). There was no pts treated with durvalumab plus gemcitabine and cisplatin. Two pts with TP53/KRAS alteration and MSI-High received pembrolizumab monotherapy, and partial response was achieved with a progression-free survival of 9.4 and 22.0 months. The median overall survival (OS) for pts treated with first-line therapy of the TP53/KRAS, KRAS, TP53, and WT/WT groups were 13.6 (95% confidence interval [CI], 11.5-15.5), 14.3 (95%CI, 9.7-25.9), 18.8 (95%CI, 16.9-20.6), and 22.7 months (95%CI, 20.4-25.9), respectively. Multivariate analysis identified TP53/KRAS alteration (hazard ratio [HR] 2.14, 95%CI 1.43-3.22, P,0.001), number of detected variants ($2) (HR 1.50, 95%CI 1.04-2.16, P=0.029), locally advanced (HR 1.72, 95%CI 1.05-2.83, P=0.033), and metastatic status (HR 1.78, 95%CI 1.39-2.28, P,0.001) as independent prognostic factors for shorter OS. Conclusions: Patients with advanced BTC with co-occurring TP53/KRAS alterations have worse prognosis. Interestingly, the presence of these co-alterations was associated with a higher likelihood of MSI-High phenotype. Research Sponsor: None.

539 Poster Session

Progression pattern and post-progression survival following atezolizumab and bevacizumab treatment in advanced hepatocellular carcinoma. First Author: Satoshi Kobayashi, Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan Background: Although the combination of atezolizumab and bevacizumab (ATZ + BEV) is a standard treatment for advanced hepatocellular carcinoma (HCC), strategies for addressing treatment failure and prognostic factors of post-progression survival remain unestablished. Methods: We conducted a multicenter retrospective study to evaluate post-progression survival following ATZ + BEV treatment in patients with advanced HCC. We classified the patients into four groups: BCLC stage B with or without new intrahepatic lesions (BCLCp-B1 and BCLCp-B2, respectively) and BCLC stage C without or with new extrahepatic lesions (BCLCp-C1 and BCLCp-C2, respectively) at the time of progression. Results: Of the 204 patients who started ATZ + BEV treatment between October 2020 and September 2022, 110 showed disease progression, with 25, 8, 55, and 22 showing the BCLCp-B1, BCLCp-B2, BCLCp-C1, and BCLCp-C2 stages of the disease, respectively. Specifically, patients with the BCLCp-B1 stage of the disease showed better overall survival than those with the BCLCp-B2, BCLCp-C1, and BCLCp-C2 stages (hazard ratios: 2.19 (95% confidence interval [CI], 0.61-7.86), 2.16 (95% CI, 1.13-4.11), and 2.97 (95% CI, 1.42-6.23) for HCC stages BCLCp-B2, BCLCp-C1, and BCLCp-C2, respectively). Via multivariable analysis, we identified the BCLCp-C1 and BCLCp-C2 stages, as well as performance status, Child-Pugh class, and alpha-fetoprotein as poor prognostic factors for post-progression survival. Conclusions: BCLCp-B1 stage was identified as a better prognostic factor for post-progression survival following ATZ + BEV treatment compared with BCLCp-B2 stage as well as BCLCp-C1 and BCLCp-C2 stages. This may help in making decisions regarding subsequent treatment after ATZ + BEV.

540 Poster Session

Genomic predictors of sensitivity to chemotherapy and immunotherapy in cholangiocarcinoma. First Author: Riya Jayesh Patel, Roswell Park Cancer Institute, Buffalo, NY Background: Cholangiocarcinoma (CCA) has seen a surge immunotherapy (IO) use. Data on the sensitivity and resistance to chemotherapy and IO in CCA is limited, making it difficult to identify predictive biomarkers for guiding treatment. We hypothesize that transcriptional signatures differentiating PD-L1 high from PD-L1 low patients (pts), can be leveraged to better understand IO sensitivity. These signatures could potentially facilitate personalized treatment strategies and mitigate therapeutic resistance. Methods: We explored transcriptomic signatures related to chemotherapy and IO sensitivity in the CCA cohort of The Cancer Genome Atlas (TCGA-CHOL). We divided the pts (n=36) into 2 groups based on PD-L1 (CD274) expression levels. Pts were designated as PD-L1 high (n=11) if PD-L1 $ average PD-L1 expression, and PD-L1 low (n=25) if PD-L1 # average expression PD-L1in the cohort. Transcriptional dysregulation was assessed by comparing transcriptional profiles of the 2 groups. Differential expression analysis, using Limma, was utilized for Gene Set Enrichment Analysis (GSEA), to assess the predicted function of transcriptional dysregulation that occurs between the 2 groups. Immune deconvolution by using the Tumor IMmune Estimation Resource (TIMER) deconvolution software to assess differences in immune infiltration and resulting scores from this analysis were used to assess how immune cell population estimates correlated with immune factors, like PD-L1 expression. Results: GSEA revealed PD-L1 low pts showed significant alterations in metabolic pathway genes that regulate cholesterol, amino acid transport and cellular respiration. As expected, GSEA revealed alterations to immune cell pathways associated with PD-L1 expression, assessed using TIMER revealed several significant correlations between immune cell deconvolution scores: CD4+ and CD8+ T-Cell (R=-0.35, p=0.02), CD8+ and neutrophils (R=0.42, p=0.009), and CD8+ and myeloid dendritic cells (R=0.3348, p=0.04). We noted significant correlations between immune cells deconvolution scores with PD-L1 expression, including PD-L1 and B Cells (R=0.54, p=0.0005), macrophages (R=0.41, p=0.01), CD8+ T Cells (R=0.43, p=0.008), neutrophils (R=0.56, p=0.0003), and myeloid dendritic cells (R=0.48, p=0.002). Significant differences in immune deconvolution scores of CD8+ T Cells, macrophages, neutrophils were noted between PD-L1 high and low pts. Conclusions: PD-L1 high pts with CCA exhibit expected differential enrichment of immune signatures. Notably, we report for the first time that CCA PD-L1 low patients uniquely enrich for differential metabolic signatures. This could lay the groundwork for understanding mechanisms that underlie IO response differences, provide valuable insights if confirmed in IO treated cohorts and serve as evidence for the utility of metabolism-targeted therapies to overcome therapeutic resistance in CCA. Research Sponsor: None.

PD-L1 as a predictor of chemo-immunotherapy response in biliary tract cancers: A systematic review and meta-analysis. First Author: Juan Jose Juarez, Beth Israel Deaconess Medical Center, Boston, MA Background: Advanced biliary tract cancers (BTCs) are rare and aggressive malignancies with limited treatment options. Recently, immune checkpoint inhibitors in combination with chemotherapy (ICI-C) gained approval as first-line therapy for unresectable or metastatic BTCs. Two large phase III clinical trials of ICI-C in BTCs did not show a significant correlation between PD-L1 expression and therapeutic response. However, in a phase II study of single-agent nivolumab, there was an association. In light of these conflicting findings, we conducted a comprehensive systematic review and meta-analysis of clinical trials investigating ICI-C in BTCs to assess whether PD-L1 expression could predict treatment response. Methods: We searched PubMed, Web of Science, EMBASE, and Cochrane databases to identify relevant studies. Patient characteristics, method of PD-L1 assessment, and measures of treatment response including hazard ratio (HR), objective response rate (ORR), progression-free-survival (PFS), and overall survival (OS) were extracted. Pooled ORR and HR were calculated using random effect model and assessed for study heterogeneity. Results: Among the 4,882 studies screened, seven clinical trials evaluating the efficacy of ICI-C in BTCs were identified. Of these trials, two randomized phase III trials report HR between PD-L1 positive and negative patients, while five phase II clinical trials reported ORR based on PD-L1 expression. Out of the 1,069 patients included in these trials, 954 underwent assessment for PD-L1 expression. 66.4% (n=634) exhibited PD-L1 expression level $ 1% as determined by either tumor proportion score (TPS) or combined positive score (CPS), while 33.5% (n=320) were classified as PD-L1 negative. Notably, 115 patients were not tested for PD-L1 expression, a variety of PD-L1 assays were used across the studies, and only some studies reported multiple PD-L1 cutoffs. Pooled analysis of two-phase III trials demonstrated that PD-L1 expression $ 1% was associated with improved OS (pooled HR 0.83, 95% CI 0.72-0.95) compared to PD-L1 , 1% (pooled HR 0.85, 95% CI 0.67-1.07). Additionally, pooled ORR from five phase II studies showed a trend towards an improved response in patients with PD-L1 expression $ 1% (pooled ORR 64%, 95% CI 52-74%) compared to PD-L1 ,1% (pooled ORR 46%, 95% CI 31-62%) with a subgroup difference p-value of 0.08. Conclusions: This meta-analysis suggests that BTCs patients with PD-L1 expression $ 1% may exhibit a more favorable response to chemoimmunotherapy, and that a majority of BTCs have this level of expression. These findings support further investigation of the use of PD-L1 as a biomarker, and in particular investigation of different PD-L1 levels, which may inform treatment for patients with relative contraindications to immunotherapy use. Research Sponsor: None.

542 Poster Session

Peri-hilar cholangiocarcinoma (phCCA): A comparative comprehensive genomic profiling study. First Author: Parth J Sampat, SUNY Upstate Medical University, Syracuse, NY Background: CCA is a heterogenous group of malignancies that arise from epithelium of the biliary tree. The comparison of the genomic landscapes that can influence therapy selection of phCCA from other types of intra-and extra-hepatic CCA (ih/ehCCA) are not well-known. We queried differences in comprehensive genomic profiles (CGP) of CCAs and comparing genomic alterations (GA) in phCCA and other types of CCA. Methods: DNA extracted from 110 cases of phCCA, 743 cases of common bile duct CCA (cbdCCA) and 9178 cases of intrihCCA underwent hybrid capture-based CGP to evaluate GA, MSI status, TMB levels, genomic ancestry, genomic signature, HRD score and germline status. phCCA cases were confirmed at surgery and pathology as originating from either the left, right or common hepatic ducts. cbdCCA cases were confirmed either by CBD biopsies or Whipple procedures. PD-L1 expression was determined by IHC using the Dako 22C3 assay using the tumor proportional score (TPS) system. Results: Patient characteristics were similar (Table ). The GA/tumor and frequencies of European ancestry were similar. Both phCCA and cbdCCA featured significantly greater frequency of ERBB2 GA than ihCCA (P=. Radiologic ORR was 28.5% (n=31), with 3.7% complete responses (CR, n=4) and 24.8% partial responses (PR, n=27). Out of 100 pts evaluable for a pathological response, 33% achieved MPR and 19% pCR. MPR was more likely in patients who had achieved a radiologic PR or CR (82%) as compared to those who did not (14% p,0.001), however linear correlation suggested an imperfect correlation between ORR and MPR (R 2 0.43, p,0.0001).

507 Poster Session

Phase 1 trial of navitoclax and sorafenib in patients with refractory solid tumors with a hepatocellular carcinoma expansion cohort. First Author: Oluwadunni Eunice Emiloju, Mayo Clinic, Rochester, MN Background: Navitoclax (ABT-263) is an oral Bcl-2 homology-3 mimetic that binds with high affinity to pro-survival Bcl-2 proteins, resulting in apoptosis. Sorafenib, an oral multi kinase inhibitor inhibits tumor angiogenesis and also promotes apoptosis. The efficacy of either agent alone is limited; however, preclinical studies demonstrate synergy with the combination of navitoclax and sorafenib. Methods: In this phase 1 pharmacokinetic and pharmacodynamic study (NCT01364051), we evaluated the combination of navitoclax and sorafenib in a dose escalation cohort of patients with refractory solid tumors, with an expansion cohort in hepatocellular carcinoma (HCC). The study agents were provided by the Cancer Therapy Evaluation Program at National Cancer Institute under CRADA. Navitoclax and sorafenib were administered continuously on days 1 through 21 of 21-day cycles. The maximum tolerated dose (MTD) was determined using the continual reassessment method.

Results: Ten patients were enrolled in the dose escalation cohort and 15 patients with HCC were enrolled in the expansion cohort. Two dose levels were tested, dose level 1 (navitoclax 150 mg daily plus sorafenib 400 mg twice daily) and dose level 2 (navitoclax 200 mg daily plus sorafenib 400 mg twice daily). At dose level 1, one dose limiting toxicity (DLT) [grade 3 aspartate aminotransferase elevation] was observed among 6 patients treated at this dose level. In a cohort of 3 patients treated at dose level 2, two DLTs were observed (grade 3 hypertension, and grade 3 rash), hence dose level 1 was identified as the MTD. Among all patients, the most common grade 3 toxicity was thrombocytopenia (5 patients, 20%): there were no grade 4 or 5 toxicities (Table ). Patients received a median of 2 cycles (range 1-36 cycles) and all patients were off study treatment at data cut off. Six patients in the expansion cohort had stable disease, 5 had progressive disease and 4 with unavailable data. There were no partial or complete responses. Drug-drug interaction between navitoclax and sorafenib was not observed. The combination of navitoclax and sorafenib did not increase induction of apoptosis compared with navitoclax alone. Conclusions: Navitoclax plus sorafenib resulted in manageable, but not ideal toxicities for continuous oral administration which precluded dose escalation. The lack of clinical benefit in the HCC expansion cohort does not support further development of this combination for the treatment of advanced HCC. Clinical trial information: NCT01364051. Research Sponsor: Mayo Clinic U01 (CA069912), Mayo Clinic UM1 (CA186686), and Mayo Clinic Comprehensive Cancer Center Support Grant (P30 CA015083).

Adverse events at least possibly related to navitoclax plus sorafenib. Background: Survival benefits for patients (pts) with ampullary cancer (AC) on adjuvant chemotherapy (ACT) remain unknown. Some studies support post-operative treatment, while others state the opposite. Also, there are no clear evidence indicating that histopathological types (pancreaticobiliary (PB-type) and intestinal (IN-type)) can be used to guide the adjuvant setting. The aim of this study is to assess the ACT efficacy in different histopathological types of ampullary adenocarcinoma (pathological stages II-III). Methods: 81 pts were enrolled in the study in total, 45.7% were males, median age was 66.0 (range 43.9-83.8) years. 36.9% were IN-type, 50.8% -PB-type, and 12.3%mixed. Almost all (97.5%) pts underwent Whipple procedure. 50 pts (61.7%) received ACT: 78.0% -5-FU-based regimen and 22.0%gemcitabine-based. Results: There was no clinical benefit in pts administered with ACT in terms of overall survival (OS): median OS was 55.5 months versus 43.6 month in observation arm; p=0.93. The ACT (FU-based or gemcitabine-based) did not correlate to improve OS in patients with IN-type: 38.0 months in patients who received ACT versus 30.5 months in those who did not; p=0.75. The ACT has shown better survival benefit in patients with PB-type compared to observation, however there was no statistical difference: 21.1 and 43.6 months, respectively; p=0.52. 5-FU-based ACT did not show any benefits compared to gemcitabine-based therapy in this subgroup. Conclusions: The use of adjuvant chemotherapy (FU-based or gemcitabine-based) in patients with II-III stage ampullary cancer was not associated with improved overall survival in our trial. There was no clinical benefit from addition of ACT either despite the heterogeneity of the tumor tissue origin (IN-type or PB-type). Research Sponsor: None.

Toxicity

509 Poster Session

Impact of baseline liver function on survival outcomes in patients with unresectable hepatocellular carcinoma (uHCC) treated with camrelizumab + rivoceranib vs sorafenib: A post hoc analysis of study CARES-310. First Author: Arndt Vogel, Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany

Background: CARES-310 study (NCT03764293) evaluated the combination of camrelizumab, an anti-PD-1 inhibitor, and rivoceranib, a highly selective VEGFR-2 tyrosine kinase inhibitor, (cam + rivo) vs sorafenib (sora) for the treatment of uHCC. Cam + rivo significantly improved median overall survival ([mOS] 22.1 months [mo] vs 15.1 mo) and median progression-free survival ([mPFS] 5.6 mo vs 3.7 mo) compared to sora. This post-hoc analysis evaluated the impact of baseline albumin-bilirubin (ALBI) grade and Child-Pugh (CP) class on survival outcomes. Methods: In this randomized, open-label, international, multicenter, phase 3 study, patients were randomized 1:1 to receive cam 200 mg IV Q2W + rivo 250 mg PO QD (n=272) or sora 400 mg PO BID (n=271). Median overall survival (mOS), median progression free survival (mPFS), objective response rate (ORR), disease control rate (DCR), and safety were assessed by baseline ALBI grade and CP class. Results: mOS, mPFS, DCR, and ORR improved with cam + rivo vs sora regardless of baseline liver function (Table ). Although treatment-related grade 3/4 AEs occurred at a greater rate in the cam + rivo arm vs the sora arm, the rate of these events was similar for patients with baseline ALBI grade 1 and grade 2 (cam + rivo, 82.1% and 81.7% vs sora, 53.9% and 54.0%, respectively). Median time-to-deterioration (mTTD) to CP class B was similar between treatment arms for ALBI grade 1 (not evaluable [NE], NE) and grade 2 (cam + rivo, 10.1 mo; sora, 10.6 mo; HR, 0.99). Conclusions: In this posthoc analysis of Study CARES-310, the efficacy of cam + rivo was superior to sora regardless of baseline liver function as measured by both ALBI grade and CP class. Despite a higher rate of grade 3/4 AEs, there was no detrimental effect of cam +rivo on liver function in patients with both well-and moderatelypreserved liver function compared to sora. These results support cam + rivo as a potential new first-line treatment option for patients with uHCC regardless of baseline liver function. Clinical trial information: NCT03764293. Research Sponsor: Elevar Therapeutics; Jiangsu Hengrui Pharmaceuticals. 126s HEPATOBILIARY CANCER Visit meetings.asco.org and search by abstract for the full list of abstract authors and their disclosure information.

Comparison of neoadjuvant treatment modalities for locally advanced intrahepatic cholangiocarcinoma. First Author: Esteban Garita, Beth Israel Deaconess Medical Center, Boston, MA Background: The only curative therapy available for intrahepatic cholangiocarcinoma (IHCC) is resection. Nonetheless, most patients (pts) are diagnosed at a more advanced stage. In this population, using neoadjuvant treatment-locoregional therapies, systemic chemotherapy, or a combination-may improve survival outcomes and downstage them to resectable. We present data comparing survival outcomes (median overall survival [mOS], median progression-free survival [mPFS] ) and resection rate (RR) among pts with locally advanced IHCC who received chemotherapy (CT-only), Y90-TARE with chemotherapy (Y90+CT) or Y90-TARE alone (Y90-only) as neoadjuvant treatment. Methods: A retrospective chart review of all pts from October 2015 to December 2022 with biopsyproven IHCC was completed. Exclusion criteria included ECOG $ 2, stage IV extrahepatic disease, and having received previous treatment for IHCC. We defined the Y90+CT arm as pts who received # 4 cycles before Y90 or chemotherapy , 8 weeks after Y90. Statistical analysis was performed with Chi-square, Fisher's Exact, and Kruskal-Wallis tests. Kaplan-Meier analysis was used for survival calculations and a Log-rank test to compare the arms. Survival is reported as median and 95% confidence interval [CI] .

Results: A total of 56 pts were included: 23 pts in the CT-only arm, 15 in the Y90+CT arm, and 18 in the Y90-only arm. The median age at diagnosis was 69 years (IQR 59-74), and 54% were male. There was no statistically significant difference in age at diagnosis or sex between the three arms. RR was 1/23 (4%), 5/10 (50%), and 7/11 (64%) in the CTonly, Y90+CT, and Y90-only arms, respectively (CT-only vs. Y90+CT, p,0. [23.3-25.3], and 24.3 months [23.0-25.6 ] for CT-only, Y90+CT, and Y90-only arms, respectively (CT-only vs. Y90+CT, p,0.03; CT-only vs. Y90-only, p,0.01). The mPFS were 3.5 months [1.1-5.9], 6.2 months [3. 8-8.6 ], and 10.5 months [8.3-12.6 ], respectively (CT-only vs. Y90-only, p,0.01; Y90+CT vs. Y90-only, p,0.02).

Conclusions: In the neoadjuvant setting, including Y90 as a treatment modality may improve survival outcomes and resection rates compared to using chemotherapy alone. Further analysis will include running the Cox multivariate regression model to control for factors that may affect treatment selection in this population. Research Sponsor: None.

511 Poster Session

A phase II trial of induction systemic mFOLFIRINOX followed by hepatic arterial infusion of floxuridine and dexamethasone given concurrently with systemic mFOLFIRI as a first-line therapy in patients with unresectable liverdominant intrahepatic cholangiocarcinoma (HELIX-1). First Author: Skye C. Mayo, School of Medicine, Department of Surgery, Division of Surgical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR Background: Most patients with intrahepatic cholangiocarcinoma (ICC) have unresectable or multifocal liver-dominant disease. Survival after first-line systemic therapy remains poor, with median progression-free (mPFS) and overall survival of 7.2 and 12.8 months, respectively. Hepatic arterial infusion (HAI) therapy with floxuridine maximizes liverspecific treatment with minimal systemic toxicity and potentially offers improved disease control when combined with systemic therapy. Methods: HELIX-1 (NCT04251715) is an investigator-initiated, first-line, single-center, single-arm phase II clinical trial for patients with liver-dominant unresectable or multifocal ICC. The trial was designed with a patient safety run-in evaluating toxicity from the combined therapy. Pre-trial screening included laparoscopy, biopsies, and PET/CT. Eligible patients were treated with systemic mFOL-FIRINOX for 4 cycles in order to select those likely to benefit from HAI. Patients with disease control on restaging proceeded to HAI pump placement and treatment with HAI floxuridine for 14 days followed by systemic mFOLFIRI on a 28-day cycle. The co-primary objectives were to assess safety of the combined therapeutic strategy and the disease control rate (DCR) at 6 months (RECIST v1.1) at end of trial (EOT). Results: A total of n=5 patients with liver-only ICC enrolled in the trial and completed the entire study protocol.

The median age was 60 years (range 42-69) with a dominant lesion size of 9.8cm (range 8.4-14.5). All patients had both right and left hemiliver involvement with a median of 9 intrahepatic tumors (range 1-15). No patients experienced grade 3 or 4 adverse events, or hepatic dysfunction leading to cessation of HAI therapy. The DCR at 6 months was 100%, with a mPFS of 18.2 months. All five patients achieved partial radiographic response (PR) while receiving HAI therapy, and remain alive with liver-only disease at a median of 18.4 months (range 12.7-20) after study enrollment. After continuing treatment with HAI and systemic mFOLFIRI beyond the EOT, two patients transitioned to HAI treatment only and then to biochemical and radiographic surveillance without therapy after demonstrating PR and CA19-9 normalization. Conclusions: Integration of HAI floxuridine with mFOLFIRI following mFOLFIRINOX induction for patients with liver-only advanced ICC is welltolerated and demonstrates longer DCR in comparison to historical controls. The combined regimen minimized systemic toxicity and allowed a large proportion of patients to transition to liver-only HAI treatment with maintained disease control. Future directions include combining HAI with new first-line systemic regimens for patients with advanced ICC. Clinical trial information: NCT04251715. Research Sponsor: None.

512 Poster Session

Evaluating local tumor destruction and wedge or segmental resection in the treatment of fibrolamellar hepatocellular carcinoma: An NCDB analysis. First Author: Christopher Reese Bine, Creighton University Medical Center, Omaha, NE Background: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare type of hepatic cancer, comprising 1% of all liver malignancies. Patients are often diagnosed in their second or third decade and often have a palpable liver mass. Treatment primarily consists of surgery and transplant, however, standardized protocols have not been well established due to its rarity. For patients who cannot receive a transplant, there are few studies examining and comparing other surgical types. Using the National Cancer Database, we aim to uncover survival and patient characteristic differences between those who receive Local Tumor Destruction vs Wedge or Segmental Resection. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with FL-HCC from 2004 to 2019 using the histology codes 8171 as assigned by the II, III and IV; p,0.001) and well differentiated tumors (p,0.001). Compared to WSR, it was associated with higher rates of therapy before and after surgery(p,0.05). There were no significant differences in tumor size, income group, adjuvant therapy type, or facility type (p.0.05) between the treatment groups. Conclusions: Receipt of WSR is associated with improved survival compared to LTD. There are distinct demographic groups which may be guiding surgical selection. Further research into this disparity and other surgical types should be examined to create better guidelines for FL-HCC patients.

513 Poster Session

Update results from ALTER-H004 study: Anlotinib combined with TACE as adjuvant therapy in patients with hepatocellular carcinoma (HCC) at high risk of recurrence after surgery: A single arm, multi-center, phase II clinical trial. First Author: Zheng Wu, Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China

Background: High recurrence rate after curative resection significantly compromised the long-term survival of patients with HCC patients (pts). TACE as adjuvant therapy was proved to improve clinical outcomes for pts with high recurrence risk factors after hepatectomy. However, the prognosis of TACE reminded unsatisfactory and controversial. Therefore, this study aimed to identify the efficacy and safety of anlotinib as maintenance adjuvant treatment following inductional TACE in pts with HCC. The update results were reported here with longer follow-up duration. Methods: HCC pts with one of the following high risk factors after hepatectomy: $5 cm and ,10 cm of tumor diameter, tumor number $3, tumor microvascular invasion M1 or M2, portal vein tumor thrombus resection (Cheng's classification I/II) were recruited. Eligible pts received cTACE treatment within 1-2 months after hepatectomy, on the 3-5th day after cTACE, oral anlotinib (12mg, qd, d1-d14, q3w) was given until disease recurrence or unacceptable toxicity. The predefined sample size was 30. The primary endpoint was disease free survival (DFS). Secondary endpoints included 1-year DFS rate, time to recurrence and safety. Results: The data cut-off date was March 2023, 29 pts were enrolled and 27 pts received at least once tumor assessment. The median follow-up was 21. 8 (IQR, 3) months. Of 27 with assessable efficacy, mDFS was 24.2 (95% CI, not applicable-not applicable) months, with 12-, and 24-month DFS rates of 72.2% (95% CI, 50.4%-85.7), and 61.8% (95% CI, 38.8%-78.3%), respectively. 18 of 27 pts (66.7%) experienced treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 4 pts (14.8%) included hypertension (7.4%), leukocytopenia (7.4%) and ascites (3.7%). No grade 4 or 5 TRAEs occurred. Conclusions: Anlotinib combined with TACE as adjuvant therapy in HCC pts at high recurrence risk exhibited encouraging efficacy and tolerable safety profile. And the conclusions needed to be confirmed in large scale clinical trials subsequently. Clinical trial information: NCT04213118. Research Sponsor: None.

Liver toxicity following reirradiation and multiple-target SBRT for primary hepatocellular carcinoma. First Author: Jacob Hall, The University of North Carolina at Chapel Hill, Chapel Hill, NC Background: Stereotactic body radiation therapy (SBRT) is increasingly used to treat hepatocellular carcinoma (HCC), but its safety in the treatment of multiple synchronous or recurrent lesions is underreported. We aim to better characterize SBRT-related hepatic toxicity in this population. Methods: We conducted a retrospective analysis of patients with primary HCC who underwent SBRT for 2 or more synchronous or recurrent liver lesions. We collected patient characteristics and dosimetric data (mean liver dose, cumulative effective volume [Veff], cumulative volume of liver receiving 15Gy [V15Gy] , and cumulative planning target volume [PTV]) along with liver-related toxicity (measured by albumin-bilirubin [ALBI] and Child-Pugh [CP] scores). We employed a linear mixedeffects model to assess the effect of multi-target SBRT on changes in ALBI.

Results: There were 25 patients and 56 lesions with median follow-up of 29 months.

Eleven patients had synchronous lesions and 14 had recurrent lesions treated with separate SBRT courses. Eight local failures occurred at a median of 8 months (range: 4 -25 months) after SBRT. Among those receiving multiple SBRT courses, there were 7 lesions with overlap of V15Gy (median V15Gy overlap: 35mL, range: 0.5 -388mL). There was no association between cumulative Veff, V15Gy, or PTV and change in ALBI. Four of 25 patients an increase of Child-Pugh (CP) score by $ 2 points, within 3 to 6 months after SBRT. Neither increase in CP nor ALBI were associated with cumulative Veff, V15Gy, and PTV. Comparing the groups that received SBRT in a single course versus multiple courses revealed no statistically significant differences in liver toxicity.

Conclusions: LiverSBRT for multiple lesions in a single or in separate courses results in worsening of CP scores or ALBI in a small percentage of patients, suggesting a low risk of RILD. Prospective studies with a larger cohort are needed to better characterize safety in this population. Research Sponsor: None.

516 Poster Session

PROOF 301: Results of an early discontinued randomized phase 3 trial of the oral FGFR inhibitor infigratinib vs. gemcitabine plus cisplatin in patients with advanced cholangiocarcinoma (CCA) with an FGFR2 gene fusion/ rearrangement. First Author: Ghassan K. Abou-Alfa, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY Background: Infigratinib (BGJ398), an oral inhibitor of fibroblast growth factor receptor (FGFR)1-3 with demonstrated clinical activity and a manageable adverse event profile in a phase 2 study in patients with previously treated, unresectable or metastatic CCA with an FGFR2 fusion or other rearrangement, represented one of the few targeted treatment options after progression on first-line therapy, as per FDA conditional approval. The confirmatory phase III trial PROOF 301 of infigratinib versus gem/cis as frontline treatment of FGFR2 Gene Fusions/Translocations CCA was early discontinued.

Here we report the efficacy and safety in the patients accrued prior to termination. Methods: Eligible patients were randomized 2:1 to infigratinib 125 mg on days 1-21 of a 28-day cycle vs intravenous gemcitabine (1000 mg/m 2 ) + cisplatin (25 mg/m 2 ) on days 1 and 8 of a 21-day cycle. The primary endpoint was progression-free survival (PFS), confirmed by blinded independent central review (BICR). Secondary endpoints included overall survival (OS), investigator determined PFS, overall response rate (ORR), best overall response (BOR), disease control rate (DCR), duration of response (DOR), and safety and tolerability. Crossover to the investigational arm was permitted at progression. Results: Over 40 months, a total of 1127 patients were pre-screened at 120 sites and 48 enrolled. In a 2:1 randomization, 29 patients received infigratinib and 19 received gem/cis. Upon progression, 2 patients crossed over from gem/cis to infigratinib. Median PFS (95% CI) by BICR was 7.4 (5.4, not evaluable [NE]) and 8.0 (3.4, NE) months with infigratinib and chemotherapy, respectively. The ORRs by BICR were 37.9 % with infigratinib and 15.8 % with gem/cis. Grade 3-4 adverse events occurred in 79.3% and 58.8% patients treated with infigratinib and chemotherapy.

Conclusions: Infigratinib showed a preliminary signal of efficacy in the first-line treatment of FGFR2-rearranged CCA, but due to early termination of the study, the power is insufficient to draw conclusions regarding its efficacy in comparison to gem/ cis. This study highlights the challenge of performing confirmatory studies in biomarkerselected subpopulations of rare tumors and the importance of exploring alternative approaches to delivering confirmatory data for regulatory purposes. Clinical trial information: NCT03773302. Research Sponsor: QED Therapeutics; Helsinn Healthcare SA.

517 Poster Session

Neo-adjuvant tislelizumab combined with lenvatinib treatment for resectable, recurrent hepatocellular carcinoma. First Author: Kuang Ming, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

Background: The persistent challenge of elevated re-recurrence rates following secondary hepatectomy complicates the prospects for improving survival in recurrent hepatocellular carcinoma (rHCC) patients. Immunotherapy combined with targeted drugs have been the first-line therapy for advanced HCC and shown good response rate in neoadjuvant situation. However, the effectiveness and safety of the combination treatment has not been reported in rHCC patients. To address this, we conducted the present phase 2 clinical trial of neoadjuvant treatments using tislelizumab in combination with lenvatinib for rHCC patients. Methods: Patients with resectable rHCC patients who had previously undergone curative treatment were enrolled. Enrolled patients were treated with 2 neoadjuvant cycles of a combination of tislelizumab 200mg intravenously every 3 weeks and lenvatinib 8mg every day (12mg for patients over 60kg) for 4 weeks. Hepatectomy was conducted in six weeks after enrollment. One month after surgery, adjuvant combination of tislelizumab and lenvatinib was started for at least one year or until disease progression or intolerance of adverse reactions. The primary objective of the trial is to evaluate one-year disease-free survival (DFS) rate, and secondary endpoints include objective response rate (ORR) as assessed by RECIST 1.1, major pathologic response (defined as over 90% tumor necrosis), and safety considerations. Results: Until Sep 30 th , 2023, a total of 14 patients have been enrolled. All participants underwent the complete neoadjuvant therapy with a combination of tislelizumab and lenvatinib before proceeding to hepatectomy. Throughout the neoadjuvant phase, 14.3% (2/14) of patients occurred adverse events below grade 3, with no severe adverse events occurring. The most common adverse events were fatigue (in 2 patients), hypertension (in 1 patient) and reduced appetite (in 1 patient). In 14 patients, 12 patients underwent R0 resection and 2 were waiting for hepatectomy. The average time from the initiation of the neoadjuvant therapy to hepatectomy was approximately 40.42 days. On the radiological front, one patient (8.3%) exhibited a partial response, while 11/12 (91.7%) displayed stable disease with 8 patients had tumor shrinkage. In terms of pathological outcomes, 25% of patients (3/12) achieved a complete response, whereas the remaining patients showed varying degrees of pathologic response, ranging from 5% to 85%. Conclusions: In summary, the dual therapy of tislelizumab and lenvatinib demonstrates encouraging safety and effectiveness as a neoadjuvant intervention for patients with rHCC. The long-term results of this combined treatment approach are eagerly anticipated. Clinical trial information: NCT04615143. Research Sponsor: None.

518 Poster Session

Expanding immunotherapy options in cholangiocarcinoma: Role of CD27 agonist in combination with PD-L1 and MEK inhibition on antitumor effect and CD8 + T cells. First Author: Frances Jenkins Bennett, Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA Background: Despite addition of PD-L1 therapy to unresectable cholangiocarcinoma (CCA) standard of care, there remains an unmet need for novel therapies. Our recent phase II trial of dual PD-L1 inhibition (PD-L1i) and MEK inhibition (MEKi) significantly improved progression-free survival (PFS). While MEKi enhances tumor antigen presentation and T cell tumor infiltration, it also impairs T cell priming and activation with notable CD27 upregulation. Our work reveals that CD27 agonists (CD27Ag) foster T cell stem-like and resident memory phenotypes, negating inhibitory effect of MEKi on CD8 + T cells. We hypothesized that addition of a CD27Ag to PD-L1i/MEKi combination therapy would rescue T cell activation and improve antitumor efficacy. Methods: Immune cells from pmel-1 mice were isolated, activated with gp100, and cultured in vitro with 100 IU/mL IL-2 and single, dual, or triple therapy with CD27Ag, cobimetinib (MEKi) and/or aPD-L1. Day 3 flow cytometry characterized CD8 + T cell phenotype and cytokine expression. Additionally, syngeneic murine CCA cell line URCCA4.3 (Kras G21D , tp53 -/-) was injected into C57BL/6 mice, subcutaneously or intrahepatic, followed by ~3 weeks of treatment with mono, dual, or triple therapy. For CD8 depletion studies, CD8-depleting antibody was given on the day prior to and following surgery and every 3-4 days afterwards. Tumor and tumordraining lymph nodes were harvested at study endpoint. Lymphocytes were characterized by flow cytometry. Results: MEKi, alone or with aPD-L1, reduced frequency of activated T cells in vitro (dose-dependent effect on CD69 + ). CD27Ag combined with MEKi maintained prominent T cell activation. Triple therapy PD-L1i/MEKi/CD27Ag significantly reduced tumor growth rate in mice versus mono or dual therapies (p,0.05). Tumorinfiltrating lymphocytes comprised a stem-like (Tcf-1 + ), effector memory (CD44 + CD62L -), and tissue resident memory (CD103 + CD69 + ) phenotype in triple therapy versus single or dual therapy (p,0.01, p,0.0001, p,0.0001 respectively). All groups had similar numbers of CD8 + stem-like cells (Tcf-1 + Tim-3 -) in draining lymph nodes, but these cells were only present in tumor from the triple therapy arm (p,0.05). Cell depletion studies showed that CD8 + T cells were required for efficacy of triple therapy in vivo. Finally, an aggressive orthotopic liver tumor model showed improved median survival in triple therapy mice versus control (37.5 days versus 29.5 days, p,0.01). Conclusions: CD27 agonism prevents the impairment of T cell activation that was mediated by MEKi. Moreover, this CD27Ag/MEKi/PDL1i triple therapy bolstered trafficking of T cells with stem-like, effector, or resident memory properties, in turn enhancing the antitumor response. This therapy is being evaluated in metastatic CCA patients in an ongoing Phase II clinical trial. Research Sponsor: None.

Comparing resection and stereotactic body radiation therapy for hepatocellular carcinoma with macrovascular invasion: A propensity score matched study. First Author: Michael Yan, Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada

Background: Macrovascular invasion (MVI) in hepatocellular carcinoma (HCC) patients is a poor prognostic factor. Current guidelines endorse systemic therapy for MVI. Local therapies present a potential for obliteration of MVI and improved survival. Surgery has been the standard local therapy at our institution, and stereotactic body radiotherapy (SBRT) has emerged as an alternative local therapy for this patient population. Methods: In this retrospective study, one-to-one optimal pair propensity score matching was used to compare outcomes of HCC patients with MVI who underwent surgery or received SBRT. Matching was done based on sex, age, ECOG, cirrhosis presence, Child-Pugh class, number of tumours, tumour volume, alpha-fetoprotein level, ALBI score, Japanese Classification of portal vein invasion, and hepatic vein invasion. Overall survival was estimated using the Kaplan-Meier method and between group differences determined using the log-rank test. The cumulative incidence of recurrence, accounting for the competing risk of death, was compared using Gray's test.

Results: Ninety of 193 patients were included after matching (45 patients in both the surgery and SBRT groups) (Table ). The SBRT group had a median OS of 15 months (95% CI: 10-38), while in the surgery group it was 24 months (95% CI: 11-81). Comparing the 12-, 36-, and 60-month overall survival (OS) rates between the SBRT group (57%, 33%, 15%) and the surgery group (58%, 37%, 34%), there was no statistically significant differences (p=0.16); the 5-year OS was double in the surgical resection group.

The 12-, 36-, and 60-month cumulative incidence of HCC recurrence in the SBRT group (47%, 73%, 75%) was comparable to the surgery group (69%, 69%, 69%) (p=0.89). Conclusions: Long term survival is possible in patients with HCC and MVI in a substantial minority of patients with HCC and MVI treated with local therapies. There was no statistical difference in outcomes; however, surgical resection resulted in numerically longer survival outcomes compared to SBRT after propensity score adjustment.

There is rationale for investigating both local therapies with systemic therapies in future clinical trials.

522 Poster Session

Salvage hepatic artery infusion chemotherapy after first-line systemic failure in patients with unresectable cholangiocarcinoma. First Author: Naaz Nasar, Memorial Sloan Kettering Cancer Center, New York, NY Background: Unresectable intrahepatic cholangiocarcinoma (IHC) is associated with poor overall survival (OS). Prior studies have suggested improved outcomes with hepatic artery infusion chemotherapy (HAIC), with or without systemic (SYS) compared to SYS alone, but the role of HAIC continues to evolve. This study compares outcome of HAIC when used as 1 st line treatment compared to 2 nd line therapy in patients with advanced IHC. Methods: In this retrospective review, 722 consecutive biopsy-proven, liver limited IHC were evaluated from 2000-2018. Patients undergoing upfront surgery or those with metastatic disease beyond regional lymph nodes were excluded. Overall survival (OS) was estimated using Kaplan-Meier methods. Cox regression model was used to examine the association of HAIC given at any time point with OS. To further dissect the timing of HAIC therapy (1 st vs 2 nd line) on OS, multi-state models using parametric Cox regression, as well as separate Cause-specific hazard model to intergrade the transition to 2 nd line HAIC from the 1 st line SYS state were used to estimate the mean survival time from diagnosis.

Results: 336 patients eligible for HAIC were analyzed: 137 patients began treatment with 1 st line HAIC (median age 63, 40% male) and 199 patients received 1 st line SYS (median age 64, 46% male). Median time to first treatment initiation was 1.8 vs 1.2 months for 1 st line HAIC and SYS, respectively. Median OS of all patients was 22 months (95% CI: 20-25 months), and HAIC given at any time was associated with reduced all-cause mortality by 34% (HR: 0.66, 95%CI: 0.52-0.84).

Multi-states analyses revealed that patients who received 1 st line HAIC had a mean OS of 33 months from disease diagnosis. Patients who transitioned to 2 nd line HAIC after 1 st line SYS had a mean OS of 36 months from diagnosis, while those who failed 1 st line SYS and continued 2 nd line SYS had a mean OS of 22 months from diagnosis. Patients who received no further treatment after 1 st line SYS had a mean OS of 9 months. Median OS from the start of 2 nd line for patients who received 2 nd line HAIC was 18 months and 8 months for patients who started 2 nd line SYS therapy.

The sites of progression of disease (POD) in different treatment groups has been described in the Table . Conclusions: HAIC treatment of unresectable liver-dominant IHC at any time was associated with reduced mortality by 34%. Mean OS in patients treated with 2 nd line HAIC did not appear to be significantly different than those receiving HAIC as 1 st line therapy and both appeared to be superior to 2 nd line SYS. The survival benefits of HAIC appear to be maintained after failure of 1 st line systemic chemotherapy. Research Sponsor: None.

Sites of progression of disease in different treatment groups. *At the time of transition from 1 st line SYS to 2 nd line SYS.

523 Poster Session

Safety and efficacy of external beam radiotherapy in hepatocellular carcinoma patients previously treated with yttrium-90 radioembolization. First Author: Kanokphorn Thonglert, University of Washington, Seattle, WA Background: Data on the safety and efficacy of external beam radiation (EBRT) after Yttrium-90 (Y-90) radioembolization for hepatocellular carcinoma (HCC) is limited. We report our experience using EBRT to treat HCC patients who were previously treated with Y-90. Methods: We analyzed 31 HCC patients who received EBRT following Y-90 treatment. Eighteen were treated with photon therapy (40-50 Gy in 5 fractions), and thirteen with proton therapy (42-67.5 Gy in 15 fractions). Twenty-four patients underwent Y-90 segmentectomies, while seven received Y-90 lobar treatment. The median administered Y-90 activity was 44.4 mCi (range 8.3-114.4 ). Results: Patients had received 1 (n=14), 2 (n=7), or $3 (n=10) prior Y-90 treatments. EBRT was administered for various reasons: poor Y-90 response in two patients, technical limitations in 25 patients, and other reasons in four patients. Ten patients had previously received Y-90 within the EBRT area, thirteen outside the EBRT area, and eight in both regions. The median tumor size was 3.8 cm (range 1.6-19.4). Twenty-seven patients had Child-Pugh (CP)-A score, three had CP-B, and one had CP-C baseline liver function. With a median follow-up of 21 months, the 2-year progression-free survival, and overall survival rates were 28%, and 43%, respectively. The 2-year cumulative incidence of local failure was 7%. CP+2 progression was observed in five patients (16%): three had Y-90 delivered outside the EBRT area and two within the EBRT area. Three patients had possible RILDrelated deaths. Grade 3+ biliary complications occurred in three patients (10%): one biloma, one liver abscess, and one biliary stricture which resulted in a possible treatment-related death. All three patients had received at least two prior Y-90 treatment overlapping with the area treated with EBRT and had tumors located near the porta hepatis. Conclusions: EBRT for HCC patients previously treated with Y-90 is feasible and offers excellent local control. Hepatic function and biliary toxicities are potential complications and should be weighed against the clinical benefits. Research Sponsor: None.

524 Poster Session

A decade of chemotherapy management in hepatocellular carcinoma: A single-center study in Latin America. First Author: Wagner Eduardo Cruz Diaz, National Institute of Neoplastic Diseases (INEN), Lima, Peru

Background: Hepatocellular carcinoma (HC) is the most common primary tumor of the liver and is a significant health problem worldwide with check-point inhibitors and oral multikinase inhibitors (TKI) as the first-line therapy for advanced diseases. While chemotherapy treatment may not be standardized in current clinical management guidelines, it remains the only available treatment option in numerous Latin American countries. Methods: A retrospective review was carried out, in patients older than 18 years, between January 2011 and December 2020. 127 patients were analyzed and identified, they had received at least one course of chemotherapy at the Instituto Nacional de Enfermedades Neoplásicas in Lima, Perú. Results: The median age was 40 years, 40 female patients (31.5%) and 87 male patients (68.5%). Among the participants, 77 patients (60.62%) were diagnosed with hepatitis B, 2 patients (1.57%) had hepatitis C virus infections, and 48 patients didn´t have viral hepatitis. 72 patients (91.13%) underwent antiretroviral treatment. Non-cirrhotic patients were 118 (92.91%) and 111 (87.4%) had a Child A score. Chemotherapy was administered as first-line treatment to 118 patients (92.91%), with 47.61% receiving 5-FU-based chemotherapy, 11.11% Adriamycin, and 8.7% Gemcitabine-based chemotherapy. A smaller subset, consisting of 8 individuals (6.29%), received sorafenib as their first-line treatment. The overall survival (OS) rates at 12, 36, and 60 months were 74.14%, 20.69%, and 1.72%, respectively. Regarding disease-free survival (DFS) rates at 12, 24, and 48 months were 28.89%, 6.67%, and 2.22%, respectively. Conclusions: In this updated data for advanced hepatocellular carcinoma, we observed a subset of patients with advanced HC achieved favorable outcomes, with a median OS of 20.37 months and a median DFS of 6.6 months. Additional research is necessary to enhance our understanding of the molecular characteristics and resistance pathways of hepatocellular carcinoma in Peru and their correlation with the favorable survival rates observed in response to chemotherapy treatment. Research Sponsor: None.

Novel GPC3-targeting radiopharmaceutical therapy for hepatocellular carcinoma. First Author: Fanching Lin, RayzeBio, Inc., San Diego, CA Background: Glypican-3 (GPC3) is a membrane-anchored oncofetal protein whose expression is largely absent in normal tissues. Significant upregulation of GPC3 protein has been observed in approximately 75% of hepatocellular carcinomas (HCC), and is associated with poor prognosis. The differential expression of GPC3 between tumor and normal tissues provides an opportunity for targeted radiopharmaceutical therapy (RPT) to treat HCC, a leading cause for cancer-related deaths worldwide. Methods: RAYZ-8009 comprises a novel macrocyclic peptide binder to GPC3, a linker, and a chelator that can be complexed with different radioisotopes. The affinity of peptide binders to GPC3 was determined by surface plasma resonance (SPR) and radioligand binding assays. Target-mediated cellular internalization was radiometrically measured at multiple time points. In vivo biodistribution, monotherapy and combination treatments with 177 Lu or 225 Ac were performed in HCC xenografts. Results: RAYZ-8009 showed high binding affinity (K D =0.7 nM) to human GPC3, with comparable affinity to GPC3 of human, mouse, canine and monkey origins, and no binding to other GPC family members. Potent cellular binding was confirmed in GPC3+ HepG2 cells, and was not affected by isotope switching. RAYZ-8009 achieved efficient internalization upon binding, with 42% internalized by 20 minutes in HepG2 cells. Biodistribution study of 177 Lu-RAYZ-8009 showed sustained tumor uptake and fast renal clearance, with minimal or no uptake in other normal tissues. Exquisite tumor-specific uptake was also demonstrated in orthotopic HCC tumors with no uptake in surrounding normal liver tissue. Therapeutically, significant and durable anti-tumor effect and survival benefit were achieved with 177 Lu-and 225 Ac-labeled RAYZ-8009, as monotherapy or in combination with lenvatinib, in GPC3+ HCC xenografts. Conclusions: Preclinical in vitro and in vivo data demonstrate the potential of RAYZ-8009 as a theranostic agent for the treatment of patients with GPC3+ HCC. Research Sponsor: None.

Both phCCA and cbdCCA featured significantly greater frequency of ERBB2 GA than ihCCA (P=.002) and lower frequencies of FGFR2 GA (P=.001) and IDH1 GA (P=.006). ihCCA featured significantly higher frequencies of FGFR2 (11.7%) and IDH1 (13.9%; P=.006) GA than either phCCA or cbdCCA. cbdCCA had a significantly higher frequency of KRAS GA than phCCA (P=.015) and ihCCA (P,.001). The KRAS G12C frequency reached 5.9% of KRAS mutated ihCCA. GA in BRAF, PIK3CA, CDKN2A and MTAP were not significantly different. TP53 GA were higher in cbdCCA than phCCA (P=0.011) and combined phCCA and cbdCCA (ehCCA) were higher than ihCCA (P=.071). MSI status, TMB levels and PD-L1 expression was similarly low in all 3 groups. Positive homologous recombination deficiency (HRD) scores based on %gLOH and high frequencies of MMR genomic signatures were similar in all 3 groups. Conclusions: phCCA appears to be a distinctive form of ehCCA featuring significantly higher frequencies of potentially targetable ERBB2 and lower frequencies of targetable FGFR2 and IDH1 mutations, when compared to ihCCA. Predictive IO markers were similarly low in both ihCCA and ehCCA. Research Sponsor: None.

543 Poster Session

The combination of CD8 and TIM3 expression to predict survival outcomes in hepatocellular carcinoma. First Author: Mitsuo Shimada, Tokushima University, Tokushima, Japan Background: CD8+ T cells have anti-tumor immunity in a variety of cancers including hepatocellular carcinoma (HCC). Tumor-infiltrating CD8+ T cells express immune checkpoint proteins and focus on a therapeutic targeting. T cell immunoglobulin and mucin domain protein 3 (TIM3) has been reported to be associated with suppression of anti-tumor immunity, poor prognosis, and tumor progression in HCC, resulting in upregulation on exhausted CD8+ T cells. As the exhausted T cells showed a decrease of effector cytokine production and cytolytic activity, leading to the tumor progression, TIM3 is one of the most important exhaustion markers. In the present study, we investigated the role of CD8 and TIM3 as a prognostic biomarker in HCC. Methods: We analyzed 474 HCC patients with clinical and transcriptomic data from The Cancer Genome Atlas (TCGA: n=359) and GSE 76427 (n=115) to examine associations between CD8, TIM3, and programmed death receptor-1/programmed cell death ligand 1 (PD-1/PD-L1) expression and survival outcomes. Each gene was divided into low-and high-expression groups using the tertiles of gene expression. Results: The patients with high CD8 and low TIM3 expression were associated with better overall survival (OS) (P=0.021 and P=0.025, respectively) in TCGA, while PD-1/PD-L1 were not associated with OS (P=0.306 and P=0.318, respectively). Moreover, the patients with high CD8 and low TIM3 expression were validated in GSE dataset (P=0.014 and P=0.009, respectively). The patients with high CD8 and low TIM3 expression were associated with improved OS compared with the overall HCC patient (P=0.008). Among the patients with high CD8 expression, low TIM3 expression (non-exhausted CD8+ T cells) was associated with better OS (P=0.009), but PD-1/PD-L1 were not associated with OS (P=0.491 and P=0.772, respectively). Finally, multivariate analysis showed that the patients withnon-exhausted CD8+ T cells were significantly superior for the survival outcomes (Hazard ratio=2.80, 95% CI=1.27-6.19, P=0.01).

Conclusions: High CD8 and low TIM3 expression is associated with better OS in HCC than PD-1/PD-L1, suggesting that CD8 and TIM3 are useful biomarkers for predicting HCC prognosis. Restoring exhausted T cells via the suppression of TIM3 is a promising strategy for cancer treatment, which become a breakthrough in the cancer immunotherapy. Research Sponsor: None.

544 Poster Session

Comprehensive clinico-molecular profile and efficacy of anti-HER2 therapy for HER2-amplified biliary tract cancer. First Author: Kanae Inoue, Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan Background: Biliary tract cancer (BTC) is an aggressive malignancy with poor prognosis and limited treatment options. The prevalence of HER2 amplification in BTC has been reported to be 5-20%, and clinical trials suggested the clinical benefit of HER2-targeted treatment in this disease subpopulation. In a global collaboration, we investigated the comprehensive clinico-molecular characterization as well as the efficacy of anti-HER2 therapy in HER2-amplified BTC. Methods: Patients with advanced BTC who received systemic therapy were included from the GOZILA and MONSTAR studies in Japan and from the COLOMATE trial in the US. Genomic alterations were detected by tissue nextgeneration sequencing (NGS), including FoundationOne CDx and TempuslxT, and plasma circulating tumor DNA NGS including Guardant360 and FoundationOne Liquid CDx. The clinico-molecular characteristics were evaluated in an exploratory cohort comprised of patients from Japan, whereas the efficacy of anti-HER2 therapy was assessed in a biomarker selected cohort with patients from both Japan and the US. Results: Of 439 patients included in the exploratory cohort, 43 (10%) had HER2 amplification. BTC with primary tumor location in the gallbladder accounted for 58% of primary sites of patients with HER2 amplification. TP53 mutation (84% vs 61%, p=0.003) and BRAF amplification (9% vs 2%, p=0.030) were significantly more frequent in patients with HER2 amplification compared to those without, and no KRAS mutation co-occurred with HER2 amplification.

There was no significant difference in overall survival (OS) between patients with and without HER2 amplification (17.7 months [M] vs 16.9 M, hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.65-1.40, p=0.799). Of 58 patients with HER2-amplified BTC included in the biomarker selected cohort (43 Japan, 15 US), 27 (47%) received anti-HER2 therapy. The median OS of patients treated with anti-HER2 therapy was significantly longer than that of patients who did not receive anti-HER2 therapy (24.3 M vs.

12.1 M, HR 0.43, 95% CI 0.23-0.82, p=0.011). Multivariate analysis also identified anti-HER2 therapy as an independent prognostic factor for OS (HR 0.42, 95% CI 0.20-0.85, p=0.015). Conclusions: HER2 amplifications were found in 10% of advanced BTC and did not represent an independent predictive factor for OS. Of clinical significance, patients with HER2-amplified BTC derive a significant benefit from anti-HER2 therapy.

Research Sponsor: SCRUM-Japan Funds.

Incidence and prognostic value of actionable mutations in early-stage resectable cholangiocarcinoma. First Author: Kailey Morgan Oppat, Emory University, Atlanta, GA Background: Targeted therapy for actionable mutations in advanced cholangiocarcinoma (CCA) has revolutionized second and third-line treatment algorithms. Their application in early stage disease is not defined. The incidence and prognostic value of actionable mutations in pts with early stage resected disease is not known. Methods: The Cholangiocarcinoma Foundation and Ciitizen (a wholly owned subsidiary of Invitae Corporation) collaboratively launched a registry platform that directly consents pts and collects comprehensive medical records. Presently, de-identified data including clinical characteristics, molecular testing, interventions, and outcomes have been extracted and standardized for research use on 400 pts. The data is longitudinal with regularly planned updates. We identified pts who underwent resection of non-metastatic disease and underwent genetic testing. Actionable mutations recorded included FGFR2 fusion/ rearrangement, IDH1 mutation, HER2 amplification, BRAF mutation, MSI-high, and TMB-high. Primary outcome was recurrence-free survival (RFS). Results: Of 400 pts, 137 underwent resection for CCA. When compared to pts with advanced disease, those who underwent resection had a similar frequency of genetic testing and presence of actionable mutations: 94.3% (n=248) vs 83.9% (n=115) and 38.7% (n=96) vs. 33.0% (n=38), respectively. When considering pts with non-metastatic, resected disease who underwent molecular testing (n=104), the mean age was 59.2 yrs, 66 (63.5%) were females, and 60 (57.7%) had intrahepatic cholangiocarcinoma (iCCA), 42 (40.4%) had extrahepatic disease, and 2 (1.9%) were not otherwise specified. The majority received molecular testing before or at time of surgery (n=89, 85.6%). Of pts with non-metastatic resectable disease who received genetic testing, 34 pts (32.7%) had actionable mutations: FGFR2: n=7 (6.7%), IDH1: n=16 (15.4%), HER2: n=5 (4.8%), BRAF: n=0 (0%), MSI-high: n=3 (2.9%), TMB-high: n=8 (7.7%). FGFR2 fusion/rearrangement and IDH1 mutations were only identified in iCCA.

Pts with an FGFR2 fusion/rearrangement were younger (49.9 vs 59.8 yrs; p=0.03) and all were female. Although not statistically significant, the presence of an FGFR2 fusion/ rearrangement was associated with nearly a doubling of median RFS (32.0 vs 17.3 mos; p=0.19) for patients with iCCA. Conclusions: In this highly selected cohort of pts with resected, early stage, non-metastatic CCA, the majority underwent molecular profiling before or at the time of surgery. As expected, FGFR2 fusion/rearrangement and IDH1 mutations were only present in iCCA. An FGFR2 fusion/rearrangement was seen in young, female pts and may have a favorable prognostic value as suggested by a trend in increased RFS. Clinical trials are needed to assess the value of administering targeted therapy to this patient population in the adjuvant or neoadjuvant setting. Research Sponsor: Abraham J. & Phyllis Katz Foundation.

546 Poster Session

Survival impact of homologous recombination deficiency in veterans with cholangiocarcinoma including mutual exclusivity with pathogenic KRAS and TP53. This study aimed to investigate DCP as a predictive biomarker of atezo/bev treatment response in HCC patients. Methods: This single-center retrospective analysis evaluated DCP and radiographic response in HCC patients who received atezo/bev in the first-line setting. DCP was measured at the time of best response evaluation and compared to day one of atezo/bev initiation. Elevated DCP was defined by .=7.5 ng/mL. DCP response was defined as a decrease of .=50% at response assessment compared with baseline.

Treatment response was evaluated based on imaging modalities including computed tomography and/or magnetic resonance imaging. Objective response rate (ORR) was defined as the percentage of patients with complete response (CR) and partial response (PR). Disease control rate (DCR) was defined as the percentage of patients with CR, PR, and stable disease (SD). No Response (NR) was defined as the percentage of patients with SD and PD. Comparisons of treatment effects were performed using two-tailed Fisher Exact Probability Test. Results: A total of 53 HCC patients treated with atezo/bev as first-line therapy were included. The best treatment responses according to radiographic evaluation were as follows: CR 3.8%, PR 22.6%, SD 52.8%, and PD 20.8%, respectively. Patients with DCP response had ORR of 69% (odds ratio, 15.75; 95% CI, 3.50-70.9; P=.0002) and DCR of 100% (P=.047). Patients with .=50% increase in DCP at response evaluation compared to day one of treatment had ORR of 4.5% and NR of 95% (P=.0035). On day one of treatment, 70% of patients had an elevated DCP. There was no difference between elevated DCP vs non-elevated DCP on day one of treatment and ORR.

Conclusions: This study found that DCP has utility in predicting response to atezo/bev for HCC patients in HBV non-endemic areas. Further studies are needed to confirm findings and evaluate the prognostic implications of DCP in HBV non-endemic areas.

548 Poster Session

Actionable molecular alterations in veterans with advanced cholangiocarcinoma. First Author: Ethan Samuel Lin, Department of Medicine, University of Wisconsin, Madison, WI

550 Poster Session

Comparison of mucosal microbiomes from biliary tract among patients with extrahepatic cholangiocarcinoma, patients with chronic cholecystitis, and healthy controls. First Author: Sora Kang, Division of Hemato-Oncology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon, South Korea Background: Cholangiocarcinoma (CCA) is a malignancy associated with a poor prognosis. Gut microbiome dysbiosis is considered to be related with multiple disease, including and cancer. However, relationship between mucosal microbiome dysbiosis and CCA remains unclear. In this study, we evaluated mucosal microbiome of patients with extrahepatic-CCA (EH-CCA) and compared it with patients with chronic cholecystitis (CC) and living liver donors who served as healthy control (HC), to understand the role of microbiome in development EH-CCA. Methods: A total of 18 patients with EH-CCA, 21 patients with CC, and 17 HC were included. During operation, swab sample were obtained from cancer tissue of patient with EH-CCA and from gallbladder in other participants, respectively. The bacterial 16S rRNA gene (V3/V4 region) was amplified using PCR and sequenced on the Illumina MiSeq platform. The QIIME 2 pipelines were used to analyze the raw data. Results: The median age were 71, 53, and 29 years for patients with EH-CCA, patients with CC, and HC, respectively. The mean number of operational taxonomic unit were significantly higher in the CCA (13,037 [SD 9,676]) compared to HC (5,045 [12,679] ; p,0.001). Among the sample from HC, the most abundant taxa at phylum level was Firmicutes (74.47%), followed by Bacteroidota (14.8%), and Proteobacteria accounted for only 2%. In the CC group, Firmicutes is most abundant (63.15%) phylum, followed by Proteobacteria (22.09%). In contrast, among the samples from CCA, Proteobacteria were the most common phylum (50.43%). Pairwise comparison of a-diversity measured by Chao1 index showed that richness was higher in samples from CC compared to other groups (vs HC, p=0.02; vs CCA, p,0.001). In terms of a-diversity measured by Shannon index, samples from cancer have lower diversity compared to healthy controls (p,0.001), however, no significant differences were found between samples from cancer and CC (p=0.1). The Principal Coordinate Analysis plot based on Bray-Curtis distance showed that all three groups formed significantly separate clusters (p=0.001). The linear discriminant analysis effect size showed that the most abundant taxa from samples from CCA were Enterobacter, Klebsiella, and Fusobacterium. In the samples from HC, Limosilactobacillus, Lachnospiraceae_NK4A136_group, and Faecalibacterium were most significant, while Lactobacillus and Pseudomonas were most abundant among the CC group.

Conclusions: This study compared the mucosal microbiome from biliary tract among patients with CCA, patients with CC, and HC. All three groups showed significantly different microbiome profiles. In CCA sample, the proportion of Proteobacteria is high, and diversity were low, suggesting mucosal microbial dysbiosis. Further studies are needed to investigate the clinical implications of microbial dysbiosis in CCA. Research Sponsor: None.

551 Poster Session

Inflammation gene signature to predict survival outcomes in hepatocellular carcinoma (HCC): A machine-learning approach. First Author: Nour Al-Bzour, Jordan University of Science and Technology, Irbid, Jordan Background: Inflammation is closely associated with HCC tumorigenesis. Understanding transcriptomic features of inflammatory response will elucidate potential therapeutic targets that could improve survival outcomes. Herein, we study the association between inflammation-based genes and survival outcomes in early-stage HCC.

Methods: Transcriptomic and clinical data of 249 patients with resectable stage I and II HCC were obtained from The Cancer Genome Atlas. 132 genes associated with acute and chronic inflammatory response were identified from the molecular signature database. Those were then used in a principal component analysis (PCA) to cluster patients into high and low inflammation groups using the median of the first PCA. Inflammation related differentially expressed genes (DEGs) between the two groups were then identified & were fit in Least Absolute Shrinkage and Selection Operator model to reduce the multicollinearity. Uni-and multi-variate Cox proportional hazard model was used to find the independent predictors of survival. PCA was applied to significant genes to calculate the inflammation score (IS) and the optimal cut-off point was chosen based on survival. Logrank test and Kaplan Meier curves were used to correlate the IS with overall survival (OS) & disease-free survival (DFS). Pearson's Chi-squared, Wilcoxon rank sum, and Fisher's exact tests were used to correlate the inflammation groups with clinical variables. Gene set variation analysis was performed to investigate enriched pathways between groups using the cancer hallmark gene sets. Results: We identified 6 inflammation-related DEGs associated with survival including: ADAM8, CCR7, FFAR3, S100A9, TNF, and TREM1. Two of those were independent predictors of survival: TREM1 & FFAR3. Based on IS cut off of 0.29 we have grouped patients into inflammation high (n=91) and inflammation low (n=158) groups. The low-inflammation group had significantly better OS & DFS (P=0.00039, P=0.039) respectively. No significant association was found between the inflammation groups and multiple variables including hepatitis B and C, alcohol and nonalcohol fatty liver disease. Stage I HCC patients had low-inflammation scores and better survival outcomes compared to stage II, indicative of an association between inflammation and HCC evolution. Pathway enrichment analysis notably showed significant enrichment in signal transduction pathways in the high inflammation group including Wnt/b-catenin, Notch, PI3K-AKT-mTOR, Hedgehog, TGFb and upregulated KRAS signaling. Conclusions: Findings from this analysis highlight the close association between inflammation and survival outcomes in early-stage HCC and support the utility of an inflammation-based gene signature to predict survival in this disease setting. Our work also sheds light on potentially targetable pathways linked to IS that deserve further exploration. Research Sponsor: None.

552 Poster Session

Identification and characterization of immunogenic neoantigens in biliary cancer (BC) and pancreatic cancer (PC). First Author: Francesca Battaglin, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA Background: Recognition of tumor neoantigens by autologous T cells activates immune surveillance and has been reported to promote sensitivity to immune checkpoint inhibitors (ICI) in mismatch repair deficient (MMRd)/microsatellite instability high (MSI-H) tumors. Neoantigentargeted reactivity has also been reported in microsatellite stable (MSS) tumors. Neoantigens are emerging targets for novel immunotherapy strategies, including tumor vaccines, in BC and PC. We aimed to comprehensively assess the spectrum of immunogenic neoantigens in BC and PC. Methods: 3728 tumor specimens (1389 BC; 2339 PC) tested at Caris Life Sciences (Phoenix, AZ) with NextGen Sequencing on DNA (720-gene panel) and RNA (whole transcriptome) were analyzed. MSI status was determined by immunohistochemistry of MMR protein and/or NGS. Immune epitope prediction was performed on translated peptide sequences harboring detected mutations using the NetMHCpan v4.0 method in the Immune Epitope Database, with HLA genotyping performed using arcasHLA. Immune/stromal cell abundance in the tumor microenvironment (TME) was quantified using the MCP Counter method. Gene expression profiles were analyzed for a transcriptional signature predictive of response to immunotherapy (T cell-inflamed signature, TIS).

Results: MMRd/MSI-H rate was 1.8% in BC and 1.4% in PC. 117219 unique peptide:allele interactions with predicted binding-level affinity for patient-specific HLA alleles were identified (48781 in BC; 71182 in PC). MMRd/MSI-H tumors had higher neoantigen load at all affinity levels compared to MSS. Only 4 recurrent neoantigens with binding affinity (observed in .10 samples) were identified in BC and derived from mutations in KRAS (3/4) and IDH1 (1/4), while 78 were found in PC, mostly associated with mutations in KRAS (53/78) and TP53 (16/78). The frequency of individual neoantigens was particularly low in MSS BC (, 2%). Across both cancer types, TIS scores positively correlated with the abundance of immune cell populations in the TME, notably cytotoxic lymphocytes (r . 0.40). Recurrent neoantigens associated with highest average TIS scores resulted from mutation of KRAS (G12D/V, 1.8%/1.5% of samples, respectively) in BC yet mean TIS scores were low (~60 th percentile overall). Similarly, TP53 (Y220C/R273C, 0.6%/0.7%, respectively) and CDKN2A (multiple variants, 0.5%) were associated with the highest yet relatively low mean TIS scores in MSS PC (~73 th percentile) compared to mean TIS scores associated with MSH3 (K383fs, 12%) and KRAS (G12D, 12%) in MMRd/MSI-H PC (~90 th percentile). Conclusions: This is the largest study to investigate the landscape of immunogenic neoantigens in BC and PC. The frequency of high-level binding affinity neoantigens was relatively low and associated with relatively lower TIS scores in MSS tumors, which may contribute to the immunogenic cold TME characterizing these tumor types. Background: HCC is one of the deadliest tumors with poor outcomes often diagnosed in late stages. Current surveillance strategies (alfa-fetoprotein (AFP) plus ultrasound (USG)) for high-risk population (HRP) have poor sensitivity (SN) and reasonable specificity (SP) of 61% and 92%, respectively. Triple phase computed tomography (CT) imaging has good sensitivity and specificity (» 90% for both) but the evidence does not support its use for routine surveillance. All these modalities do not have prognostic (survival) value. We attempted to develop a non-invasive, cfDNA-based tests to improve the diagnostic value of the current standard of care modalities (AFP and USG) and help in predicting the outcomes at diagnosis. We hypothesized that RNA and gene expression in HCC tissues is a surrogate for epigenome (DNA-methylation changes). Methods: We curated a 21-gene cfDNA ep-Sig from the literature with a proven prognostic value.

Evidence suggests epigenetic changes in every gene of this panel affect HCC outcomes influencing clinicopathological characteristics (large tumor size, vascular invasion, advanced staging) or early post-operative recurrence, and survival. We compared RNA and gene expression of the genes in the ep-Sig between normal (NT) and HCC tissues using a web-based tool, TNMplot.com that uses the data from the Gene Expression Omnibus of the National Center for Biotechnology Information (NCBI-GEO) or Cancer Genome Atlas (TCGA), Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and The Genotype-Tissue Expression (GTEx) repositories was used create this tool. It uses Mann-Whitney or Kruskal-Wallis tests to compute statistical significance. Results: RNA expression of all the genes from the ep-Sig was significantly in HCC than NT (1.133, . Gene expression was 19/21 genes was higher in HCC tissues (1.15, p=1.3e-08). The other 2 genes were not detected in the tested samples. Conclusions: Our ep-Sig which has a proven prognostic value and reliable prevalence in HCC patients. This study is the first step in developing clinically useful blood-based test that can revamp the current diagnostic and screening practices when used alongside AFP and USG. Research Sponsor: None.

554 Poster Session

Extrahepatic cholangiocarcinoma: Genomic variables associated with anatomical location and outcome. First Author: William A Preston, Memorial Sloan Kettering Cancer Center, New York, NY Background: Genomic determinants of outcome in intrahepatic cholangiocarcinoma have become clear but remain ill-defined in extrahepatic cholangiocarcinoma (ECA). We aimed to clarify the genomic alterations that define ECA, analyze differences between perihilar (PCA) and distal (DCA) disease, and determine clinicopathologic and genomic factors associated with survival.

Methods: Patients with EHC with tissue available for targeted next-generation sequencing at Memorial Sloan Kettering Cancer Center were identified. Differences between PCA and DCA were compared, stratified by disease extent and treatment. Associations between genomic alterations and clinicopathologic features and outcomes were analyzed. Univariable and then multivariable cox proportional hazards regression were used to compare survival, which was reported from operation in resected patients and from diagnosis in non-resected patients. Results: Two-hundred-twenty-four patients (n=127 PCA, n=97

555 Poster Session

Galectin-9 as a regulator of immune interactions in the tumor microenvironment and novel therapeutic target in biliary tract cancer. First Author: Emilie AK Warren, Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA Background: While results of the TOPAZ-1 trial led to inclusion of anti-PD-1 therapy with standard of care gemcitabine/cisplatin chemotherapy for patients with unresectable biliary tract cancer (BTC), the improvement in overall survival is modest: 12.8 vs 11.5 mos. Identification of novel immunotherapeutic strategies remains a high priority. We discovered Galectin-9 (Gal-9), a carbohydrate-binding protein, is expressed in BTC; it has various immunosuppressive effects, including induction of apoptosis in T cells upon binding to its receptor Tim-3. Defining the role of Gal-9 in the BTC microenvironment will inform how to leverage it as a novel therapeutic target. Methods: Tissue microarrays (TMAs) were constructed from tumors of 66 patients who underwent curative-intent resection of BTC from 2000-2015 at our institution. These TMAs underwent immunohistochemical staining for CD4, CD8, Gal-9 & Tim-3; the percentage of cells staining positive for each marker was quantified. For each marker, martingale residual plots and bias-adjusted log rank tests were used to identify a cut-off value of "low" versus "high" expression where survival difference was maximal. For in vivo mouse experiments, the syngeneic BTC cell line URCCA4.3 was injected subcutaneously into the flank of C57BL/6 mice, followed by 3 weeks of treatment with anti-Galectin-9 or anti-Tim-3 antibody alone or in combination with anti-PD-1 antibody.

Tumor-infiltrating lymphocytes (TILs) were analyzed by flow cytometry. Results: Median overall survival (mOS) was significantly improved in patients with high Gal-9 expression in their tumors, compared to those with low (32.5 mos vs 17.6 mos, p=0.018). However, when patients with high Gal-9 expression were further stratified according to Tim-3, patients with both high Gal-9 & high Tim-3 expression had significantly worse mOS than those with low Tim-3 (22.7 mos vs 113.9 mos, p=0.031), implying that interaction between Gal-9 and Tim-3 wields significant impact on TIL function. There was no difference in OS based on Tim-3 expression alone. When mice bearing BTC tumors were treated with Gal-9 or Tim-3 antibody monotherapy, there was no significant change in tumor growth versus control, but when either was used in combination with PD-1 inhibition, there was a significant reduction in tumor burden at study endpoint. Mice treated with either dual therapy had a significant decrease in CD4 + T reg and increase in CD4 + effector memory TIL populations compared to monotherapy (p,0.05). Conclusions: This study provides unique insight into the role for targeting the Gal-9/Tim-3 pathway in BTC. Our clinical data highlights that co-expression of these markers in BTC tumors is associated with significantly worse OS. Our in vivo preclinical studies demonstrate that blockade of either Gal-9 or Tim-3 synergizes with PD-1 targeted antibodies for superior anti-tumor efficacy. Research Sponsor: None.

556 Poster Session

Integrated multi-omics profiling to dissect the spatiotemporal evolution of metastatic hepatocellular carcinoma. First Author: Yun-Fan Sun, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China

Background: Comprehensive molecular analyses of metastatic hepatocellular carcinoma (HCC) are lacking. Methods: Here, we generated genomic, transcriptomic, and T cell repertoire data coupled with digital pathology and digital spatial profiling of 257 primary, 28 relapsed, and 176 metastatic regions from 182 HCC patients.

Results: Primary tumors rich in hypoxia signatures tended to give rise to polyclonal dissemination, which was associated with a poor clinical outcome. Genomic divergence between primary and metastatic HCC was high, and early dissemination was prevalent. The remarkable neoantigen intratumor heterogeneity observed in metastases was associated with decreased T cell reactivity, which may have resulted from disruptions to neoantigen presentation. We identified macroevolutionary somatic copy number alterations as highly selected events driving metastasis. Furthermore, we found that subclonal Wnt pathway mutations were not selected during spreading, whereas subclones without Wnt mutations showed a strong selective advantage for metastasis and were characterized by a reactive microenvironment rich in activated fibroblasts favoring an invasive tumor cell phenotype. Finally, metastases without Wnt mutations exhibited higher enrichment of immunosuppressive B cells that mediated terminal exhaustion of CD8+ T cells via HLA-E -NKG2A checkpoint axis. Conclusions: Collectively, our results provide a multi-dimensional dissection of the complex evolutionary process of metastasis. Research Sponsor: None.

Genomic and immune landscape of biliary tract cancers with ARID1A, PBRM1, and BAP1 alterations. First Author: Gentry Teng King, University of Washington Fred Hutchinson Cancer Center, Seattle, WA Background: Alterations in ARID1A, PBRM1 and BAP1 subunits of the SWI/SNF complex are common in biliary tract cancers (BTCs) and have been implicated in tumor microenvironment (TME) immunomodulation. However, there is heterogeneity in outcomes, with PBRM1 and BAP1 conferring improved survival vs worse survival with ARID1A. We explored relationships between ARID1A, PBRM1 and BAP1 alterations with putative immunotherapy biomarkers and genomic co-alterations. Methods: We examined BTC patients in the Tempus database with ARID1A, PBRM1 and BAP1 alterations. Co-alterations were identified through next-generation sequencing (NGS) using the Tempus xT assay, a targeted, tumornormal-matched DNA panel that detects SNVs, indels, and CNVs in 648 genes, as well as chromosomal rearrangements in 22 genes with high sensitivity and specificity. Samples additionally underwent whole transcriptome RNA-seq via the Tempus xR assay (Tempus Labs, Chicago, IL). Immune biomarkers explored include MSI-H, PD-L1, Tumor Mutation Burden (TMB), and immune cell infiltration by RNA sequencing. Parameters were analyzed between two groups: BTC with ARID1A, vs BTC with PBRM1 and/ or BAP1 alterations. Results: 696 BTC patients with ARID1A, PBRM1 and BAP1 alterations were included.

Overall, there was low frequency of MSI-H (3.2%), PD-L1-positivity (5.7%) and TMB .10 mt/Mb (4.7%). Among the two groups, there was a higher proportion of MSI-H patients in ARID1A BTC vs PBRM1 and/or BAP1 BTC (4.9% vs 1.4%, p=0.01). Macrophages were the predominant immune cell (46%), followed by CD4+ T-cells (23%) and NK cells (12%). CD8+ T cells were the least encountered (5%). B-Cells were seen more in ARID1A vs PBRM1 and/or BAP1 (9% vs 6%, p ,0.001) while macrophages were more frequent in PBRM1 and/or BAP1 vs ARID1A (49% vs 44%, P ,0.001). Co-alterations in SMAD4, TP53, ARID2 and KRAS were more frequent in ARID1A BTC while IDH2 and NRAS were more common in PBRM1 and/or BAP1.

Within the PBRM1 subgroup, TP53 was most frequently encountered (33%), while CDKN2A alterations were most frequently encountered in BAP1 BTC (35%) (Table 1 ). Conclusions: This is the largest known data set exploring the genomic and immune landscape of BTC with ARID1A, PBRM1 and BAP1 alterations.

Macrophages were the dominant immune cell TME and may be a target of interest. Co-alteration profile is distinct between ARID1A-vs PBRM1-and/or BAP1-altered BTC. Research Sponsor: None.

Co-alterations in BTC with ARID1A and PBRM1 and/or BAP1.

Gene

558 Poster Session

Real-world analysis of patients with advanced gastrointestinal (GI) cancers harboring inactivating TSC1 and TSC2 alterations using the Foundation Medicine genomic database. First Author: Dustin A. Deming, University of Wisconsin Carbone Cancer Center, Madison, WI Background: Genomic profiling of GI tumors can identify potentially actionable genetic alterations, ultimately leading to better outcomes in patients who currently have few treatment options. In exploratory biomarker analyses of patients with perivascular epithelioid cell tumors treated with the mTOR inhibitor nab-sirolimus (AMPECT, NCT02494570), those with inactivating alterations in the tumor suppressor genes TSC1 or TSC2 (critical negative regulators of mTOR activity) had confirmed responses (8/9 patients with inactivating TSC2 alterations and 1/5 patients with inactivating TSC1 alterations). PRECISION 1, a currently enrolling tumor-agnostic study, will evaluate nabsirolimus in patients with TSC1 or TSC2 alterations. To enumerate the frequency of these alterations in GI cancers, we analyzed data from a real-world genomic database. Methods: Next-generation sequencing (NGS) data from Foundation Medicine's genomic database of patients with advanced cancer were analyzed using the FoundationInsights web-based platform to identify patients with GI cancers who had inactivating TSC1 or TSC2 alterations (short variants [base substitutions, insertions and deletions], rearrangements, and copy number deletions). Tumor mutational burden (TMB), microsatellite instability status and other mutations were also characterized in this group of patients. Results: As of 29 March 2022, tumor tissue NGS data were available for 5816 patients with GI cancers bearing alterations in TSC1 or TSC2. Of these, 1642 patients had at least one inactivating alteration. The GI tumor types that most frequently expressed inactivating alterations in TSC1 or TSC2 were hepatocellular carcinoma (alterations in 6.5%); colorectal adenocarcinoma (1.7%); gastrointestinal stromal tumors (1.7%); and cholangiocarcinoma (1.6%). Of all 1642 patients, 688 were female, and most (74%) were 51-80 years of age when the sample was obtained. Of patients with inactivating TSC1 and TSC2 alterations, 37.6% were in TSC1 and 62.9% were in TSC2 and included short variants (31.3% and 48.4%), rearrangements (2.7% and 6.6%), and copy number deletions (3.5% and 7.4%), respectively. TMB was low (,6 mutations/megabase) in 58% of patients, and most patients had microsatellite stable (MSS; 71.3%) tumors. Other commonly mutated genes in this cohort were TP53 (62.7%), APC (38.5%) and KRAS (30.4%). Conclusions: TSC1 and/or TSC2 alterations were commonly observed in GI cancers. These cancers were frequently microsatellite stable and of low TMB suggesting that these are actionable alterations that may be candidates for targeted therapy. This hypothesis is being tested in the PRECISION 1 (NCT05103358) trial which is open for enrollment or just-in-time clinical trial sites and available to patients with GI cancers harboring TSC1 or TSC2 alterations. Research Sponsor: Aadi Bioscience.

559 Poster Session

Agrin as a prognostic biomarker in hepatocellular carcinoma. Results: Mean circulatory plasma agrin levels were higher in HCC patients (n=79) (7.97 ng/ml, SD 5.8) when compared to controls (4.27 ng/ml, SD 1.03). ECOG PS . 2 was linked to higher agrin conc. (mean: 10.5 ng/ml, p 0.007). While agrin levels in healthy individuals did not change with smoking history, the mean agrin levels were significantly higher in smokers (9.49 ng/ml) vs nonsmokers (6.84 ng/ml) (p 0.0001) amongst HCC patients. Agrin displayed a strong positive correlation with AFP (correlation coefficient (r) 0.31944, p 0.0137). Multivariate cox regression models indicated that agrin conc. of . 9.3 ng/ml had greater predictable survival outcomes (Hazard ratio (HR) 8.51, p ,0.001) when compared to elevated AFP levels (HR 1.55, p 0.25) (Table ). HCC patients with lower agrin conc. (4.9 to 6.3 ng/ml) exhibited a one-year survival rate of 63% & a median survival time of 16 months, while those with higher agrin conc. exceeding 9.3 ng/ml had significantly lower one-year survival rate of 14% & significantly shorter median survival time of 3 months (p 0.002). Conclusions: Our results suggest that agrin levels as a prognostic indicator fare better than AFP levels. Thus, further studies should be done to explore this as a therapeutic target and as a biomarker of response to targeted therapies. Research Sponsor: None.

560 Poster Session

Impact of next-generation sequencing in biliary tract cancer treatment. First Author: Priya Goyal, Georgetown University, Washington, DC Background: Incorporating molecular profiling in BTC treatment has increased. With this study, we aimed to analyze the impact of molecular profiles on the survival of patients with BTC. Methods: This is the retrospective analysis of patients with biopsyproven biliary tract cancer at our comprehensive cancer center GI oncology clinic from 2018-2022. Only patients with continued care at Lombardi Comprehensive Cancer Center were included in the study. Results: Of 217 patients screened; 160 patients were included in the final analysis. The mean age of the cohort was 63 years, and the majority were females (55%). In the order of frequency, intrahepatic cholangiocarcinoma (77.5%) was the most common type of cancer followed by extrahepatic cholangiocarcinoma (15.6%), and carcinoma of the Gallbladder (6.9%). Molecular profiling was performed in 49.4% of the patients and actionable mutations for FDA approved treatments or clinical trial enrollment were found in 42 patients (26.3%) of the patients. The spectrum of actionable mutations in decreasing order of frequency was KRAS (n=11), FGFR2 (n=9), IDH-1 (n=8), Her-2neu (n=5), BRCA1/2 (n=5), & PD-L1(n=4). Patients who underwent molecular profiling had significantly better survival (4365 months vs. 2564, p 0.013). Notably, patients with actionable mutations had even better survival as compared to the rest of the cohort (5268 months vs. 2667 months, p 0.019). Conclusions: BTC exhibits diverse genetic alterations. Patients who underwent molecular profiling as a part of the treatment plan had better survival. Identifying actionable mutations was associated with even better survival. Research Sponsor: None.

Serologic, radiographic, and tissue-based markers associated with major pathologic response after treatment with neoadjuvant immunotherapy in patients with resectable hepatocellular carcinoma. First Author: Michael Brian LaPelusa, The University of Texas MD Anderson Cancer Center, Houston, TX Background: Neoadjuvant immunotherapy can induce a major pathologic response (MPR) in patients with resectable hepatocellular carcinoma (HCC), which may be associated with prolonged recurrence-free survival. This study aimed to understand which variables correlate with achieving an MPR. Methods: Patients with resectable HCC who received either neoadjuvant nivolumab plus ipilimumab or nivolumab alone and underwent surgery were included. 18 patients had baseline and post-treatment computed tomography, alpha-fetoprotein (AFP), and elastography. 17 of these patients had baseline and post-treatment tissue available for immunohistochemistry. Patients were classified into two groups: MPR, defined as necrosis of .70%, and no MPR. Data was summarized using descriptive statistics and compared using Wilcoxon rank sum test. P value ,0.05 was considered statistically significant.

Results: Statistically significant differences in objective response (OR) and changes in CD8, Granzyme B, and PD-1 expression were identified upon comparison of patients with an MPR to those without an MPR (Table 1 ). Additionally, numerical differences in baseline tumor size, change in AFP, and both non-tumor and tumor liver fibrosis (at baseline, after treatment, and interim change) were identified upon comparison of patients with an MPR to those without an MPR. Conclusions: Our data show that large baseline tumor size, greater OR, reduction in AFP, increase in liver and tumor fibrosis, and increase in CD8, Granzyme B, and PD-1 expression after receipt of neoadjuvant immunotherapy are associated with achieving an MPR in patients with resectable HCC. Research Sponsor: None.

562 Poster Session

Survival and progression-free survival in patients undergoing curative resection for intrahepatic cholangiocarcinoma. First Author: Nazli Begum Ozturk, Beaumont Hospital, Royal Oak, MI Background: Intrahepatic cholangiocarcinoma (iCCA) is a relatively rare but increasingly prevalent form of primary liver cancer. Surgical resection with negative margins is the mainstay of the treatment for patients with resectable-iCCA. However, given the rarity of iCCA and its low resectability rate, well-defined prognostic markers and outcomes for patients undergoing curative hepatectomy are lacking. We aimed to analyze the characteristics and outcomes of patients undergoing liver resection for iCCA. Methods: All consecutive patients with confirmed iCCA who underwent hepatectomy between 7/2006-3/ 2023 at our institution were included. Patients who received neoadjuvant therapy were excluded. Demographic, clinical, radiological, histopathological, recurrence, and survival data were collected. Overall survival was calculated from the date of liver resection to the date of death or last clinical encounter. Continuous variables are reported as median and interquartile range (IQR) 1 and IQR3, and categorical variables as counts and percentages.

Are adverse events (AEs) during first-line FOLFIRINOX (FFX) more frequent in real-world (RW) patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who do not proceed to second-line therapy? First Author: Ravi Kumar Paluri, Wake Forest Baptist Health, Winston-Salem, NC Background: mPDAC patients (pts) that tolerate 1L FFX may increase their survival with 2L therapy, most often gemcitabine + nab-paclitaxel (GnP). However, some pts discontinue treatment due to the toxic effects of 1L FFX and consequently experience disease progression and reduced survival. Reasons for discontinuation are typically not available in RW sources. To assess whether AEs are more frequent per unit time in pts that stop treatment after 1L, we calculated the RW incidence rates (IRs) of AEs during 1L treatment for two RW cohorts: mPDAC pts treated with 1L FFX and no 2L (FFX-only) vs. pts treated with 1L FFX and 2L GnP (FFX + GnP). Methods: This retrospective observational study utilized the Ontada Clinical Data View: Pancreatic Cancer database. Adult pts diagnosed with mPDAC between November 2018 and November 2021 who initiated treatment with 1L FFX #90 days from their metastatic diagnosis were included. Diarrhea, fatigue, nausea and vomiting, and neuropathy were available in the data as ungraded AEs abstracted from clinician notes. Hematologic and hepatic AEs were based on observed lab values and were graded according to the Common Terminology Criteria for AEs v5. Pts were required to have $1 year of followup unless death occurred first. We evaluated differences in IRs of AEs per pt-month of 1L treatment for statistical significance using the test-based method. Results: 587 pts met study inclusion criteria. 300 pts received FFX-only prior to death or end of follow-up, while 287 received FFX + GnP. For FFX-only vs. FFX + GnP pts, median age was 66 vs. 64 (IQR: 59-71 vs. 57-69), 57% in both groups were male, 70% vs. 69% were white, 55% vs. 62% had an ECOG of 0-1, and 8% vs. 3% had an ECOG of 2. Median 1L duration of therapy (DoT) was 2.1 (IQR: 0.7-5.0) vs. 4.6 months (IQR: 2.1-7.4). Among ungraded AEs, fatigue was more frequent per pt-month of 1L tumors, and fewer positive regional lymph nodes were significantly associated with increased odds of receiving surgery. Additionally, treatment at an academic facility and private insurance status was associated with significantly higher rates of surgery. Patients who did not receive surgery were significantly older, had later stage disease, higher co-morbidity scores, and larger tumor size. Income level and race had no effect on treatment selection. Conclusions: This study found that surgery alone without adjuvant therapy is independently associated with improved survival. Favorable clinical characteristics may be contributing to this discrepancy in survival. Further exploration of treatment strategies in PCT may benefit patients through the creation of definitive treatment guidelines to manage this disease. Research Sponsor: None.

632

Prognostic value of the CRM status in pancreatic ductal adenocarcinoma: Data from a regional cancer registry. First Author: Philipp Morakis, Geschäftsstelle Qualitätskonferenzen bei der Klinischen Landesregisterstelle Baden-Württemberg GmbH, Krebsregister Baden-Württemberg, Stuttgart, Germany Background: Ductal pancreatic adenocarcinoma (PDAC) still has a dismal prognosis even when deemed resectable. A cancer free resection margin (R0) is associated with a more favourable prognosis than the presence of tumour cells at resection margin (R1). However, the precise definition of the R0 status is still a matter of debate in PDAC. For a more accurate determination of R0 in PDAC the concept of circumferential resection margins (CRM) has been introduced. However, an international standardized nomenclature of CRM is still missing, and the clinical value of the CRM concept is not yet fully established. Here we evaluate whether the CRM status as defined in the national German S3 guideline is an independent prognostic factor in PDAC using data from the regional cancer registry of the State of Baden Württemberg in Germany. Methods: Data from the cancer registry of the State of Baden-Württemberg, Germany were collected, using documented patients diagnosed with invasive ductal adenocarcinoma of the pancreas between 2015 and 2020. The R-status was assessed according to the national German S3 guideline with R0 wide/CRM-when CRM is . 1mm, R0 narrow/CRM+ when CRM is £ 1 mm from the tumour and R1 when tumour cells are found at the resection margin. . . Conclusions: This study highlights a marked increase in the incidence of early-stage PDAC, surpassing the overall incidence increase, suggesting improving diagnostic capabilities over the last two decades. Furthermore, the substantial improvement in 5-year survival rates for stages IA and IB indicates progress in the management of early-stage PDAC. These findings emphasize the importance of continued efforts in early detection and treatment strategies for PDAC.

634 Poster Session

Intra-operative radiation for pancreatic cancer: Initial experience at the Hadassah Medical Center. First Author: Gianella Cornejo, Hadassah Medical Center, Jerusalem, Israel Background: Prognosis following surgery for pancreatic cancer (PC) remains poor.

Local recurrence is common and negatively impacts survival rate. In an effort to improve local control and potentially improve survival, we have adopted a strategy of adding intra-operative electron radiation therapy (IOeRT) to selected patients undergoing pancreatic resection (PR) for PC. Here we report our initial experience with this treatment modality. Methods: 14 patients (10 male, 4 female), age between 44 -81 years (mean 66.17), who underwent PR (Head 7, Body7) between 1/2021-1/2023 were included in this analysis. Patients selected for IOeRT included patients that according to surgeon assessment were at risk not to achieve satisfactory resection margins by surgery alone. All had resectable or borderline resectable disease according to standard criteria. 8 patients underwent pre-op chemotherapy followed by stereotactic body radiotherapy (SBRT) to a dose of 25-40 Gy in 5 fractions to the tumor and regional lymphatics followed by PR (5 Whipple, 3 distal pancreatectomy) and IOeRT, 3 patients received preop SBRT followed by PR (3 distal pancreatectomy) + IOeRT, 2 patients underwent PR (whipple 1, distal pancreatectomy 1) + IoeRT, and 1 received neoadjuvant chemotherapy followed by SBRT only and did not undergo surgery due to tumor progression. Immediately following resection, mobile IOeRT accelerator using a 40-80mm applicator with a level of 0-15 degrees was directed at the tumor bed deemed at high risk for recurrence. 10-20 Gy was delivered using 6-8 MeV electrons to the 90% isodose line at the discretion of the treating radiation oncologist. Data including serial imaging, genomic analysis, radiation protocol, complications, pathological results and outcome was collected for analysis. Results: Mean follow up was 9.7 months (2-21). 8 patients are alive: 7 pts with no evidence of disease and 1 pt with liver metastases. 6 patients died: 4 with distant metastatic disease, 1 from disease progression prior to surgery and 1 from early post-op sepsis. Negative surgical margins were achieved in 10 patients of which 2 mutated BRCA gene carriers showed complete pathological response (both who received combined neoadjuvant chemotherapy followed by SBRT

641 Poster Session

The impact of a pancreatic cancer multi-disciplinary clinic on patient-centric outcomes. Through a consensus process, the LHN arrived at four aims to achieve by December 31, 2023. The aims are: Patients screened for 1) clinical trials will increase from 39% to 100%, 2) palliative care will increase from 30% to 100%, 3) enzyme need will increase from 37% to 100%, and 4) goals of care assessed will increase from 57% to 100% . CCC established measures to guide improvement toward the aims, which are tracked using a registry. Sites co-developed operational definitions for each measure and implemented new practices to identify and manage all patients with pancreas adenocarcinoma who enter their care. For each aim, each care center identified their current processes for screening, documented their desired future processes, tested changes to close gaps, and standardized successful changes. Many began with a subset of their population, or in a single clinic, and are working to expand to additional populations and settings. CCC facilitates best practice sharing among LHN peers and data sharing. Care centers have had access to the following supports: 1) quality improvement coaching, 2) topical workgroups, 3) peer workgroups, 4) network-wide webinars, 5) summaries of best practices to adapt locally, 6) data at site and network levels, and 7) a community platform for documentation and collaboration.

Results: There are 2,443 patients in the CCC registry. All sites report data on patients discussed in pancreas clinic or tumor board and are working to include their full PC population. Data analyzed using Shewhart control charts (p-charts) show improvement at an aggregate level across all aims. A January 2021-December 2022 baseline includes 1,218 patients. Care centers began testing changes in January 2023, and 1,225 patients have been included since. The percent of patients screened for clinical trials, enzyme need, and palliative care has shifted above the upper control limits for at least six months. The percent of patients with goals of care assessed shifted above the upper control limit for five months. Just one data point outside the upper control limit (UCL) signifies nonrandom variation. Conclusions: These aims put our 14 care centers on a path to delivering measurably improved care for patients through better access to nutrition, clinical trials, and palliative and supportive care services. A LHN is a model of collaboration and community building that can successfully transform care delivery at scale for patients with PC. Research Sponsor: 1440 Foundation.

646 Poster Session

A qualitative exploration of perceptions and experiences towards physical activity among patients with pancreatic ductal adenocarcinoma undergoing treatment. First Author: Tyra Nguyen, Cedars-Sinai Medical Center, Los Angeles, CA Background: Patients with pancreatic ductal adenocarcinoma (PDAC) experience significant symptom burden due to the disease and its treatment, thus limiting their ability to participate in physical activity (PA) and engage in daily activities. PA can have many physical and psychosocial benefits, and exploring its value and how to deliver it to patients with PDAC could support their health and well-being. Therefore, the objective of this qualitative research was to explore perceptions and experiences of PA among PDAC patients undergoing active treatment. Methods: Qualitative semi-structured interviews were conducted with individuals with PDAC. Participation was optional and open to individuals in the DigiSTEPS prospective trial evaluating associations between PA measures, performance status, and patient-reported outcomes (NCT03757182). Interviews were conducted virtually. Data were analyzed using inductive thematic analysis. Results: Ten patients (50% male, 80% white, mean age=70 years) participated in the interviews. While clinical approaches may often be informational and seek to educate PDAC patients regarding the importance of PA and the benefits of PA participation, findings suggest that participants understand the benefits of PA and are interested in being active. However, cancer symptoms and treatment-related side effects are substantial barriers that are hard to surmount. A further barrier was the dissonance in self-perceptions, particularly the contrast in their functional abilities and body composition pre-to post-cancer diagnosis. We identified four action items to support patients in overcoming these barriers: clinicians can leverage trust in their team to provide evidence-based information on how to be active; distribute wearable activity monitors which can increase motivation; harness virtual PA opportunities during more symptomatic periods; and provide PA trainers with cancer knowledge to tailor programming. Conclusions: This research highlights the importance of tailoring PA discussion and approaches based on a PDAC patient's phase in the cancer survivorship continuum, their stage at diagnosis, and treatment type. In addition, clinical teams and trainers should consider patient concerns related to body image and develop programs that address the barriers identified in this research. Clinical teams may benefit from integrating access to counselling psychologists to address these concerns and promote PA in positive and adaptive ways. Clinical trial information: NCT03757182. Research Sponsor: Internal CSMC Funding; Pancreatic Cancer Action Network.

160s PANCREATIC CANCER Visit meetings.asco.org and search by abstract for the full list of abstract authors and their disclosure information.

Pharmacogenomic study of gemcitabine on the safety and efficacy in patients with metastatic pancreatic cancer (GENESECT study): Analysis of a subpopulation. First Author: Takashi Yokokawa, Department of Pharmacy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan Background: In the GENESECT study, we examined the relationships between gemcitabine (GEM) metabolism-related germline genetic polymorphisms (GPs) and treatment efficacy and safety. However, no significant GPs were found because approximately 70% of the patients were treated with nab-paclitaxel, which has a different metabolic process than GEM. In the present study, a subanalysis including only GEM monotherapy patients was performed. Methods: Of the 159 patients analyzed in the GENESECT study, only the GEM monotherapy patients were selected. The endpoints were the carbohydrate antigen 19-9 (CA19-9) response (reduction $50% from the pretreatment level at 8 weeks), progression-free survival (PFS), and overall survival (OS) in relation to GPs from the viewpoint of efficacy, and neutropenia $Grade 3 and thrombocytopenia $Grade 3 in relation to GPs from the viewpoint of safety. The analyzed genes included those encoding GEM transporters and metabolic enzymes (SLC29A1, ABCC5, CDA, DCK, RRM1/2), and a tumor cell proliferation enzyme (COX-2). Statistical analysis included univariate and multivariate logistic regression analyses. The significance level was set to 5%. Results: Data of 50 patients were analyzed. AA genotype in ABCC5 1146A.G (rs7636910) was associated with a significantly higher percentage of CA19-9 responses compared to AG/GG (52.9% vs 21.2%, p = 0.023), and the association remained significant on multivariate analysis (OR: 6.255, p = 0.014).

Patients with AA genotype in ABCC5 1146A.G tended to be associated with PFS, but this was not statistically significant (HR: 0.464, p = 0.074). On the other hand, there was no significant association between CA19-9 responses and DCK-1205C.T (rs4694362), TT/CT genotype in DCK-1205C.T was significantly associated with prolonged PFS compared to CC (median, 127 vs 48 days, p = 0.002), and the association remained significant on multivariate analysis (HR: 0.153, p = 0.028). No GPs were significantly associated with OS, and the presence of second-line chemotherapy was the only relevant factor. In terms of safety, no GPs were significantly associated with either neutropenia or thrombocytopenia. Conclusions: The results suggest that ABCC5 and DCK might be related to the efficacy of treatment with GEM, but further research is needed. Clinical trial information: UMIN000012720. Research Sponsor: None.

652 Poster Session

Neoadjuvant SBRT plus regional nodal irradiation with concurrent capecitabine for patients with resectable pancreatic cancer: Survival analysis of prospective phase 1 trial. First Author: Mustafa Basree, Department of Human Oncology, University of Wisconsin-Madison, Madison, WI Background: Radiation may have a role in management of patients with early-stage pancreatic cancer. However, the role of regional nodal irradiation (RNI) is not well defined despite the high frequency of occult nodal disease. The goal of this trial was to evaluate the safety and feasibility of stereotactic body radiation therapy (SBRT) to primary disease with RNI, combined with capecitabine as a neoadjuvant approach for patients with resectable pancreatic cancer. Updated survival analysis will be presented here. Methods: This is a prospective, single institution, phase IA/B dose-escalation trial that enrolled patients with biopsy-proven, resectable, pancreatic adenocarcinoma between 2014 -2019 (NCT1918644). Patients were enrolled into one of the 3 cohorts with escalating dose levels. Neoadjuvant SBRT to the primary tumor was delivered in 5 fractions of 5, 6, or 7 Gy with concomitant capecitabine. All patients received RNI 5 Gy x 5 fractions. Our initial report found no dose-limiting toxicities (Witt et al IJROBP 2020). Clinicopathologic features were summarized using descriptive statistics. Kaplan-Meier curves were employed for survival analysis. Results: Seventeen patients were enrolled on the protocol with sixteen evaluable (94.1%). Thirteen (76.5%) patients proceeded to surgery.

662 Poster Session

Non-responders to neoadjuvant chemotherapy in pancreatic adenocarcinoma: Characteristics and outcomes. First Author: Brendan Hagerty, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY Background: For patients with localized pancreatic adenocarcinoma, resection and systemic therapy remain the mainstays of curative-intent treatment. Neoadjuvant chemotherapy has been frequently employed with the goals of addressing systemic disease early and improving patient selection for surgery. Those who do not respond to neoadjuvant therapy present a challenge with a lack of randomized data to aid in decision making. Here we sought to define the characteristics and outcomes of those patients to guide clinical practice. Methods: This was a single-institution retrospective cohort study using a prospectively maintained database of those diagnosed with pancreatic adenocarcinoma. Patients included in the study were those who received neoadjuvant chemotherapy. Non-responders were defined as those with both no radiographic and no biochemical response at the first re-assessment after initiation of therapy. Results: A total of 176 patients were identified who were treated with neoadjuvant chemotherapy with curative intent. Of those, 42 (23.8%) patients had no evidence of either radiographic or biochemical response. Of those patients, 14 were upfront resectable (33.3%) and 20 were borderline resectable (47.6%). An additional 8 (19%) were locally advanced. Most patients received FOLFIRINOX as a first line chemotherapy agent (n = 25, 59.5%). A total of 12 (28.6%) patients underwent neoadjuvant radiation therapy. A total of 19 (45.2%) proceeded to surgery and two of those were found to be unresectable at exploration, resulting in 17 (40.5%) who ultimately received curative-intent resection. Exactly half (n = 21) of the patients had their chemotherapy switched (CS). Of those who had CS, 11 (52.4%) had evidence of local tumor progression on their initial restaging scan compared to just 3 (14.3%) of those who did not (p = 0.02). Additionally, patients who had CS had higher incidence of vascular involvement on their initial scan (90.5% vs 52.3%, p = 0.051). A total of 6 (28.6%) who underwent CS had subsequent biochemical response compared 4 (19.0%) of those who did not. Ultimately, 6 (28.6%) of those who had CS ultimately proceeded to surgery compared to 13 (61.9%) of those who did not (p = 0.062). Interestingly, there was no significant difference in median overall survival between those who had CS (18.6 months) and those who did not (19.9 months, p = 0.525).

Conclusions: Non-responders to frontline neoadjuvant systemic therapy present a clinical challenge and have poor rates of curative-intent resection. Chemotherapy switch was employed mostly in cases with worse prognostic factors and thus infrequently lead to resection. Despite this, patients who underwent CS had similar overall survival to those who did not. These data suggest there may be a role for chemotherapy switch in those who do not respond to front line chemotherapy. Research Sponsor: None.

663 Poster Session

Phase II study of the safety and efficacy of discontinuing pegfilgrastim for pancreatic adenocarcinoma treated with FOLFIRINOX. First Author: Masahiro Yanagi, Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan Background: The original FOLFIRINOX regimen (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) for pancreatic ductal adenocarcinoma (PDAC) is associated with a high risk of febrile neutropenia (FN), and pegfilgrastim has been used to reduce the risk. However, it remains unclear how long pegfilgrastim needs to continue. This study evaluated the safety and efficacy of FOLFIRINOX after discontinuing pegfilgrastim in PDAC patients. Methods: This prospective phase II trial included patients with PDAC who received the first three courses of FOLFIRINOX, with primary pegfilgrastim prophylaxis for FN, and did not experience FN.

666 Poster Session

Results of the safety and tolerability of ivaltinostat plus capecitabine in the phase 1b portion of a phase 1b/2, dose-escalation, randomized, multicenter study in the maintenance (maint) setting in patients with metastatic pancreatic adenocarcinoma (mPDAC). First Author: Evan Justin Walker, University of California, San Francisco, San Francisco, CA Background: The standard of care for patient (pts) with advanced or mPDAC typically consists of mFOLFIRINOX or gemcitabine/nab-paclitaxel used in the front-line setting until disease progression (prog) or toxicity. A tolerable maint therapy (tx) that can effectively delay disease prog while preserving quality of life with minimal cumulative toxicity is highly desirable. There is no standard main tx. Ivaltinostat (ival) is a pan-HDAC (histone deacetylation) inhibitor that increases histone acetylation (HA), suppresses PDAC cell proliferation, and promotes apoptosis in PDAC cell lines. Preclinical data demonstrated synergy with 5-FU/capecitabine in mouse models. The phase 1b study will determine an optimal combination of ival and cape followed by a randomized P2 trial of ival plus cape vs cape alone in the maint setting for pts with mPDAC who have not progressed on front-line mFOLFIRINOX. Methods: Key eligibility criteria for P1b include: locally advanced or mPDAC; at least 1 prior line of tx regardless disease prog; ECOG PS 0-1; and no known gBRCA1/2 mutation. Dose-limiting toxicities (DLT) in 3 dose levels of ival, (60, 125, and 250mg/m2 iv weekly on days 1 and 8) in combination with cape (1000mg/m2 po BID on days 1-14) of a 21-day cycle will be evaluated. The primary objective is to evaluate the safety, tolerability and determine the recommended phase 2 dose (RP2D) as well as pharmacokinetics (PK) of ival and cape. Results: As of the date of data-cut, 32 pts had been enrolled at the 60 (7 pts), 125 (14 pts) and 250 (11 pts) mg/m2 dose level, 8 were screen failures and 9 still ongoing with a goal of at least 6 DLT-evaluable pts per dose level. Average prior lines of tx was 3.6 (range 1-5). The median age was 68 (range 51-83) and 21(66%) were males. No DLTs were observed across the 3 dose levels. SAEs occurred in 2 pts that were not related to study drugs. Both ival and cape-related TEAEs were similar except palmar-plantar erythrodysesthesia syndrome (PPES) 9(28%) attributed to cape; fatigue, diarrhea and nausea were the only TEAEs occurred .15%. Two pts had ³grade 3 diarrhea, another pt had caperelated PPES. The TEAE profile was similar across the dose levels. At the time of data-cut there were 6 deaths among pts who discontinued study due to prog. Among 15 pts who had been evaluated for response since baseline, the best ORR were 11 SD(73.3%), 1(6.7%) no RECIST-measurable evidence of disease and 3 PD(20% 23 patients proceeded to surgery of which 6 the radical surgery was abandoned due to extent of malignancy The overall median survival time was 20.6 months with a 90% confidence interval of (12.9 months to 24.9 months). The median survival time was 23.7 months with 90% confidence interval of (12.9 months to 24.9 months) for FOLXFOX-A, and 20.5 months with a 90% confidence interval of (8.9 months to NA) for the AG arm Conclusions: We have demonstrated that these 2 regimes can be utilised in the neoadjuvant setting with surgery being undertaken safely following therapy (there was no surgical mortality and morbidity is in line of other international series). Further work is ongoing to identify potential biomarkers which may lead to better patient selection for a neoadjuvant approach. Clinical trial information: ISRCTN34129115. Research Sponsor: CRUK; BMS/Celgene.

670 Poster Session

FOLFIRINOX plus high intensity focused ultrasound for locally advanced/ borderline resectable pancreatic ductal adenocarcinoma: A prospective single arm phase II trial. First Author: Dong Ho Lee, Department of Radiology, Seoul National University Hospital, Seoul, South Korea Background: FOLFIRINOX has been the standard regimen for locally advanced pancreatic cancer (LAPC) for palliation and borderline resectable pancreatic cancer (BRPC) for neoadjuvant treatment. According to the results of animal studies, concurrent use of high intensity focused ultrasound (HIFU) and chemotherapy can enhance the drug delivery to the target tissue. In this phase II trial, we aimed to evaluate the safety and therapeutic efficacy of FOLFIRINOX plus HIFU for patients with LAPC or BRPC. Methods: This study was designed as a prospective single center phase II trial (Study identifier: NCT05262452). We prospectively enrolled 60 patients (M:F=35:25; median age, 67.0 years old) with LAPC (n=23) or BRPC (n=37). The median tumor size was 4.0 cm (Interquartile range, 2.7-4.6). All patients were treated by FOLFIRINOX (oxaliplatin, 85mg/m 2 of body-surface area; irinotecan, 180mg/m 2 ; leucovorin, 400 mg/m 2 ; and fluorouracil, 400 mg/m 2 given as a bolus followed by 2400 mg/m 2 given as a 46-hour continuous infusion) every 2 weeks until disease progression. HIFU was combined in the first 4 cycles of chemotherapy with following parameters: intensity of 2.0 kw/cm 2 , duty cycle of 1%, exposure time of 3 seconds and PRF of 10Hz. Follow-up contrast enhanced CT was taken every 4 cycles for the response evaluation using response evaluation criteria for solid tumor 1.1. Overall survival (OS) and progression-free survival were estimated using Kaplan-Meier method. All analyses were intention-to-treat.

Results: Two patients withdrew the consent, and two patients could not complete planned 4 cycles of FOLFIRINOX plus HIFU treatment owing to sepsis from severe neutropenia related to chemotherapy.

679 Poster Session

Exocrine pancreatic insufficiency as a possible predictor of pancreatic cancer development. First Author: James Gore, Department of Internal Medicine, Ochsner Health, New Orleans, LA Background: Chronic and acute pancreatitis are established risk factors for pancreatic cancer. Chronic pancreatitis and pancreatic cancer are also common causes of exocrine pancreatic insufficiency (EPI), which is characterized by inadequate pancreatic secretion of exocrine digestive enzymes. Although the association between EPI and pancreatic cancer has been thought to be linked by preceding chronic pancreatitis, it is unclear if EPI, regardless of etiology, is a risk factor or early marker for pancreatic cancer or cancer in general. Methods: This is a retrospective observational study utilizing the electronic health records of Ochsner Health System, Louisiana, over a 3-year period from January 2017 to January 2020 to identify patients with a diagnosis of EPI by ICD-10 codes. Two cohorts were reviewed: patients with EPI (n=677) and patients with pancreatitis (n=1852). Both history of acute and/or chronic pancreatitis were included in the pancreatitis cohort. The cohorts were compared based on cancer prevalence at the start and end of the 3 year observation period. Results: In the EPI cohort, the cancer prevalence was 15.95% (108) at start, and 43.9% (297) at end, (p,0.05); and pancreatic cancer prevalence at start was 6.65% (123) and 29.8% (552) at end (p,0.05). In the pancreatitis cohort, the cancer prevalence was 5.4% (100) at start and 15.9% (294) at end (p,0.05); and pancreatic cancer 0.8% at start and 5% at end (p,0.05). Conclusions: Over a 3 year period, the rise in prevalence of general cancer and pancreatic cancer was higher in the EPI cohort compared to the pancreatitis cohort.

Additionally, there was a statistically significant 2.8-fold increase in prevalence of cancer diagnosis and 4.5-fold increase in prevalence of pancreatic cancer diagnosis in the EPI cohort over the 3 year observation period. Though this is an observational study, it suggests the possibility that EPI, regardless of etiology, may be an independent predictor/risk factor for the development of future cancer in general and pancreatic cancer in particular. In addition it appears that this risk potential is substantively greater than that from a history of pancreatitis alone. Research Sponsor: None.

680 Poster Session

Prevalence of cancer and alcohol use in patients with exocrine pancreatic insufficiency compared to patients with cystic fibrosis. First Author: James Peeples, Department of Internal Medicine, Ochsner Health, New Orleans, LA Background: Cystic fibrosis (CF), the most prevalent genetic disorder among persons of European decent, is an autosomal recessive disorder due to CFTR gene mutations which lead to abnormally viscid exocrine secretions of the pancreas and other exocrine glands of the body. Exocrine pancreatic insufficiency (EPI) is a condition seen in ~85% of CF patients, in which the pancreas is unable to secrete adequate amounts of digestive enzymes. Although most patients with CF develop EPI, not all cases of EPI are caused by CF. Other risk factors for EPI include acute or chronic pancreatitis which may be triggered by alcohol, among other etiologies. Some studies suggest alcohol use as a possible independent risk factor for development of various cancers. Given these associations, we sought to characterize the prevalence of both alcohol use and cancer in patients with EPI vs patients with CF. Methods: A retrospective observational study was performed using electronic health records in Ochsner System, Louisiana, over a 3 year period: January 2017 to January 2020. Two cohorts were reviewed: patients with EPI excluding CF (n=596) and patients with CF (n=81). Results: While there was no significant difference in the prevalence of cancer at start vs end of the 3 year observation period in the CF cohort (4.1% at start, 7.2% at end), the prevalence of cancer was significantly greater among patients in the EPI cohort, both at start and end of the 3 year period: 15.95% at start, 43.9% at end (p ,0.05). Also, while there was no significant change in alcohol use over the 3 year period for the CF cohort, the prevalence of alcohol use was significantly lower in CF cohort (0.45% at start, 2.2% at end) compared to EPI cohort which showed significant increase in alcohol use over the observation period: 7.7% at start vs 16% at end (p ,0.05). Conclusions: There was a significantly higher prevalence of cancer in the EPI cohort compared to the CF cohort; while this may be due to higher prevalence of pancreatic cancer associated with EPI compared to CF, it does not explain the entirety of this observation. Not only was there a significantly higher prevalence of alcohol use in EPI cohort compared to CF cohort, but over the 3 year observation there was a 2-fold increase in prevalence of alcohol use within patients who already had a diagnosis of EPI. Within the EPI cohort, the observed increase in cancer prevalence and the increase in alcohol warrant further investigation into which factors unique to EPI patients without CF may modulate these social and health risk indices.

A transcriptomic approach to explore the immune landscape of patient with pancreatic ductal adenocarcinoma with prognostic impact.

683 Poster Session

Early molecular assessment to predict prognosis in patients who respond to chemotherapy on initial imaging in pancreatic cancer. First Author: Fumiaki Watanabe, Saitama Medical Center, Jichi Medical University, Saitama, Japan Background: It is helpful to predict early the response to anticancer drugs in nonresectable solid tumors. The purpose of this study is to evaluate whether circulating tumor DNA (ctDNA) helps predict prognosis in patients with non-resectable pancreatic cancer who have received first-line FFX or GnP therapy and have responded to treatment (CR, PR, SD groups) on initial imaging. Methods: A total of 61 patients with nonresectable pancreatic cancer treated with FFX (N=22) and GnP (N=39) as first-line therapy were included in the study. Before and after chemotherapy treatment (median 42 days, after two courses), KRAS-mutated ctDNA was measured using droplet digital PCR with CA19-9. We defined the Responder group as those with CR, PR, or SD other than PD on initial imaging and the molecular assessment as the change in KRASmutated ctDNA before and after treatment. (1) No appearance of KRAS-mutated ctDNA before and after treatment was defined as molecular negative (mNT); (2) disappearance of KRAS-mutated ctDNA or decrease in copy number after treatment was defined as molecular response (mR); (3) new appearance of KRAS-mutated ctDNA or increase in copy number after treatment was defined as molecular progressive disease (mPD). We investigated whether the increase or decrease of CA19-9 before and after treatment (Increase group, decrease group) and the molecular assessment were useful as prognostic factors in the Responder group. Results: Male: female = twenty-nine: thirtytwo. There were fourteen patients in the locally advanced group and forty-seven patients in the distant metastatic group, both of whom were considered non-resectable. Thirtyeight patients received any second-line treatment. We previously performed a phase II trial of P with carboplatin (C) and paclitaxel (Pxl) vs C and Pxl alone in metastatic PDAC (NCT01280058). Although P did not improve progression-free survival compared to C and Pxl alone, some exceptional durable responses were seen in the P arm. Low levels of carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) mRNA expression were associated with prolonged PFS in P-treated pts (p=0.05) and there was a 3.3 times higher fold change in Interferon-inducible transmembrane protein 3 (IFITM3) expression in the pts doing poorly versus responders (nominal p,0.05) in P arm. Here we investigate mechanisms of resistance to P infection mediated through CEACAM6 and IFITM3 in a panel of pancreatic ductal adenocarcinoma cell lines. Methods: Prior studies noted CEACAM6 and IFITM3 may restrict cell entry of certain enveloped viruses. CEACAM6 and IFITM3 protein levels were measured in PDAC cell lines using Western blot. Flow cytometry was used to assess P infectivity. We have generated multiple knockdowns of CEACAM6 and IFITM3 in PDAC cell lines to determine changes in P infectivity and other inflammatory signalling pathways. Live cell imaging was used to assess cell viability. Results: Basal expression of CEACAM6 was measured in a panel of 4 PDAC cells (PANC10.5, HPAFII, BxPC3, CFPAC1). Panc10.05 had low basal expression nor could expression be induced by 24hr P infection. All other cell lines showed moderate to high basal expression that was inducible. P infectivity at 24hrs was significantly higher in Panc10.05 cells compared to high CEACAM6 expressing cell lines.

There was varying basal expression of IFITM3, however all cell lines showed IFITM3 induction when exposed to P. Of the 3 cell lines that also expressed high levels of CEACAM6 (HPAFII, CFPAC1, BxPC3), low basal expression of IFITM3 was strongly associated with increased sensitivity to P infection and decreased viability at 72hrs, which could be induced by knockdown of IFITM3 in high expressing cell lines. Neither C or Pxl altered levels of CEACAM6 or IFITM3 in any of the four cell lines. Conclusions: High CEACAM6 and IFITM3 play a role in P viral infectivity across multiple pancreatic cell lines, confirming results obtained in translational datasets. Further analysis is ongoing to elucidate mechanism and identify pathways to alter expression of CEACAM6 and IFITM3 and enhance P infectivity in future trials. Research Sponsor: None.

Molecular characterization of small extracellular vesicles in patients with pancreatic cancer treated with neoadjuvant chemotherapy followed by stereotactic body radiation (SBRT). First Author: Ravi Kumar Paluri, Wake Forest Baptist Health, Winston-Salem, NC Background: Currently, pancreatic cancer (PanC) is one of the serious gastrointestinal diseases, and more than 90% of the patients die within five years of diagnosis. Therefore, to improve PanC-related mortality, new therapeutic and diagnostic/prognostic measures are urgently needed. In this substudy, we examined the usefulness of plasma small extracellular vesicles (sEV) to discover molecular biomarkers associated with treatment response and overall survival from the plasma samples collected on a prospective clinical trial assessing the efficacy of SBRT following chemotherapy in pancreatic cancers (NCT03600623). Methods: PanCpatients (n=22) with locally advanced and borderline inoperable disease were recruited at the University of Alabama Comprehensive Cancer Center. They were administered either FOLFIRINOX (5-FU, folinic acid, oxaliplatin, and irinotecan) or paclitaxel (gemcitabine-nab-paclitaxel) for 2 months followed by SBRT (33 Gray in 5 fractions). The primary objective of this single-center pilot study was to evaluate the safety and tolerability of this treatment regimen. Further, blood was collected at baseline and, at the end of chemotherapy and radiotherapy. sEV were isolated from archived plasma samples by an established ultracentrifugation method and characterized for size and concentration by nanoparticle tracking analyses (NTA), shape and size by transmission electron microscope (TEM), and surface expression of exosomal tetraspanin markers (CD63, CD9, and CD81) and a PanC marker (CA19-9) by nano-flow cytometry. Lastly, sEV in longitudinal plasma samples were characterized for the expression of specific PanC-related miRNAs (miR196a-5p, miR155-5, miR194-5p, miR301-3p, miR21-5p, miR1246, and miR34a-5p) by real time-PCR (RT-PCR). Results: Neoadjuvant FOLFIRINOX and gemcitabine-nab-paclitaxel followed by SBRT were safe and well tolerated by most patients. NTA data showed that the ultracentrifugation method yielded highly pure sEV (with average diameter of ,200 nm) from archived baseline and longitudinal plasma samples. TEM analysis further confirmed the shape and size of the isolated sEV. Nano-flow cytometry showed the expression of exosomal markers, CD63, CD9, and CD81, as well as PanC marker CA19-9 on the surfaces of sEV. The median spleen V 5Gy , V 10Gy , V 15Gy , and V 20Gy were 12.8% (range, 0 -77.5%), 1.9% (range, 0 -66.2%), 0% (range, 0 -54.5%), and 0% (range, 0 -39.2%), respectively. The median ALC at a median 25.5 days before A-RT was 1.39 no./mL (range, 0.24 -3.00 no./ mL), and this decreased to 0.85 no./mL (range, 0.20-2.45 no./mL) a median 6 weeks after A-RT. Grade 2 lymphopenia (G2L) prior to vs. after A-RT was 6.9% vs. 27.7% (p,0.001). Grade 3 lymphopenia (G3L) prior to vs. after A-RT was 1.0% vs. 13.9% (p,0.001). No grade 4+ lymphopenia was observed. Significant factors on multivariable analysis (MVA) for G2L were age (OR: 1.05, 95% CI 1.01-1.09, p=0.019), male vs. female (OR: 0.30, 95% CI:0.11-0.82, p=0.019), and T1-3 vs. T4 (OR: 0.27, 95% CI: 0.10-0.71, p=0.007); ICT duration, target volume dose/volume, and spleen dose were not significant on univariate analysis (UVA). No factors were significant on UVA for G3L, but a trend was observed for T1-3 vs. T4 (OR: 3.5, 95% CI: 0.91-13.42, p=0.067) and spleen V 5Gy (OR: 1.44, 95% CI: 0.85-3.26, p=0.065). Conclusions: To our knowledge, this is the first study to evaluate spleen dose and ALC changes after A-RT for PDAC. We observed a similar incidence of grade 2+ lymphopenia compared to prior 5-fraction NA-RT studies. There was a trend towards significance of higher spleen V 5Gy being associated with a higher probability of G3L. We are evaluating whether grade 2+ lymphopenia is associated with long-term clinical outcomes after A-RT for inoperable PDAC. Research Sponsor: None.

687 Poster Session

Kinetics of CA19-9 decline in a randomized phase III study of irinotecan liposome injection, oxaliplatin, 5-fluorouracial/leucovorin (NALIRIFOX) or nab-paclitaxel plus gemcitabine (GEM+NABP) in patients who have not previously received chemotherapy for metastatic adenocarcinoma of the pancreas (NAPOLI 3). First Author: Sreenivasa R Chandana, Cancer & Hematology Centers of Western Michigan, Grand Rapids, MI Background: The NAPOLI 3 study (NCT04083235, N = 770) reported that NALIRIFOX improved overall survival (OS) vs Gem+NabP with manageable toxicity in 1L treatment of metastatic pancreatic adenocarcinoma. We explored changes in CA19-9 levels and their potential associations with efficacy as an important tumor marker in pancreatic adenocarcinoma. Methods: In NAPOLI 3, CA19-9 was evaluated at baseline and every 8 weeks until patients discontinued study treatment. The detection limit of CA19-9 was 8000 kU/L in this study. The Cox proportional hazards regression and logistic regression were employed to investigate the relationship between CA19-9 decrease and OS, progression-free survival (PFS), and overall response rate (ORR). Results: Patients with evaluable CA19-9 (levels =, 8000) at baseline and additional measurements at weeks 8 and 16 were included in the analysis (NALIRIFOX, n = 179; Gem+NabP, n = 194). The median baseline CA19-9 level was 378.0 and 409.7 kU/L for the NALIRIFOX and Gem+NabP arms, respectively. Overall, patients with (vs without) any CA 19-9 decrease by week 16 had a higher ORR (59.9% vs 35.2%; p = 0.002), a longer median PFS (9.2 vs 6.2 months; p , 0.001) and a longer median OS (14.2 vs 8.7 months; p = 0.005), respectively in a pooled analysis of the treatments. In the NALIRIFOX arm, patients with any CA19-9 decrease by week 16 had a higher confirmed ORR of 65.1% compared with those without at 42.4% (p , 0.001), a median PFS of 9.5 vs 7.1 months (p , 0.001) and a median OS of 15.4 versus 8.4 months (p = 0.004), respectively. In the Gem+NabP arm, patients with CA19-9 decrease by week 16 had a higher ORR of 55.5% compared with those without at 23.8% (p = 0.012), a median PFS of 7.6 versus 5.8 months (p , 0.001) and a median OS of 13.7 versus 11.9 months (p = 0.235), respectively. Conclusions: CA19-9 decrease by week 16 has the potential to be an early prognostic factor for OS, PFS and ORR. The results should be interpreted with caution as a considerable percentage of patients were excluded due to non-evaluable CA19-9 that exceeded the lab detection limit of 8000 kU/L. Clinical trial information: NCT04083235. Research Sponsor: Ipsen.

688 Poster Session

Results: A total of 83 patients (43 male, 40 female) were included in the final analysis. The median age at resection was 67 years (58.0-74.0). Histologically proven liver disease was present in 30.12% and liver cirrhosis was present in 9.63% of patients. Among all patients, hypertension was present in 61.44%, diabetes mellitus in 25.30%, inflammatory bowel disease in 7.22%. The median tumor size was 4.4 cm (3.0-6.2). Tumor histologic grade was 55.42% moderately differentiated tumor, 37.3% poorly differentiated tumor, and 7.22% well differentiated tumor. Of all patients, 37.66% had lymph node invasion, 35.61% had perineural invasion, and 30.76% had vascular invasion on liver histology. Positive surgical margins were present in 20.73% of patients. The duration from liver resection to the last follow-up or death was 1.6 years (0.80-3.20). The 1-, 3-, and 5-year recurrence-free survival rates were 72.78, 34.95, and 15.88% respectively. The 1-, 3-, and 5-year overall survival rates were 90.9%, 65.9, 44.2%, respectively. Advanced iCCA stage at diagnosis (p,0.001), presence of lymph node metastasis (p=0.03), vascular invasion (p=0.02), and age,50 (p=0.01) were associated with significantly worse overall survival. There was no statistically significant survival difference between patients with concurrent liver disease and those without (6.88 vs 4.35 years, p=0.46.). Conclusions: Our results demonstrate that iCCA carries a substantial risk of recurrence despite curative resection. The presence of advanced stage at diagnosis, lymph node involvement, vascular invasion, and age,50 were associated with significantly worse overall survival. Liver disease had no significant effect on the survival outcomes. Predictive markers of recurrence and survival in patients vary in the literature and remain to be validated. Research Sponsor: None.

563 Poster Session

Surrogate endpoints for overall survival in advanced hepatocellular carcinoma: A meta-analysis. First Author: Yacob Saleh, Princess Margaret Cancer Centre, Toronto, ON, Canada

Background: Recent advances in systemic therapies have resulted in improved overall survivals (OS) for patients with advanced hepatocellular carcinoma (aHCC). The most commonly utilized primary endpoint for phase III trials in aHCC is OS. A robust surrogate endpoint (SEP) can reduce time and financial costs of future trials and accelerate regulatory approvals of new therapies. We conducted a literature-based meta-analysis to evaluate SEPs for OS in aHCC. Methods: Randomized controlled trials evaluating systemic therapies in aHCC published 2007 -2023 were identified through a systemic literature search of Cochrane and Medline databases as well as of abstracts presented at ASCO and ESMO meetings. Hazard ratios (HR) for OS and progression-free survival (PFS) and time to progression (TTP) were extracted. DORR was calculated as the difference in overall response rates (ORR) between control and experimental arms. Pearson correlation and mixed-effects meta-regression analyses were performed. Surrogate threshold effect (STE) was determined for each comparison when possible. A p , 0.05 was considered to be statistically significant. Results: 26 trials were identified in the firstline setting with 14,827 patients and 11 trials in the subsequent-line setting with 5,316 patients. In first-line trials, immunotherapy (IO) is associated with higher ORR than other agents (p=0.003). There are statistically significant correlations between HRs of PFS/ TTP/DORR and OS (Table ). The relationship between HR-PFS and HR-OS persists in trials with or without IO, but only in trials enrolling , 30% patients of non-viral aetiologies. In subsequent-line trials, there are statistically significant correlations between HRs of PFS/TTP and OS (Table ). STE for HR PFS is 0.68 and 0.87 respectively for 1 st and subsequent line trials. Conclusions: There are moderate to strong correlations between PFS and OS in aHCC in first-line and subsequent line trials. STE for HR-PFS of 0.68 in first-line and 0. Background: Ulcerative colitis (UC) is correlated with gastrointestinal cancer. While the exact mechanism is unknown, it is thought that a chronic inflammatory state may result in the development of malignancies including cholangiocarcinoma. Patients with UC that develop cholangiocarcinoma usually have a poor prognosis and early detection is key to improve survival. Methods: We used the 2016-2019 National Inpatient Sample (NIS) database, the largest allpayer inpatient care database in the United States, to stratify all patients admitted with a diagnosis of cholangiocarcinoma with and without ulcerative colitis, to further characterize their epidemiological characteristics.

Results: There were at total of 46,001 patients with a diagnosis of cholangiocarcinoma studied. Of these patients with cholangiocarcinoma, 401 had concomitant UC (0.87%). Individuals with UC in the database had an increased association with cholangiocarcinoma (OR=7.67, 95% CI 6.96-8.46) compared to those without UC. Patients with cholangiocarcinoma and UC tended to be younger (57.8 vs. 67.9 years old without UC), male (69.51% vs. 53.23% without UC), with private insurance (57.5%) vs. patients without UC who predominately had Medicare (59.46%). Patients with cholangiocarcinoma and UC had on average fewer Charleston Comorbidities (64.63% with 3 comorbidities) vs. patients without UC (74.52% with 3 comorbidities). Of patients with cholangiocarcinoma and UC, 65.85% were Caucasian (vs. 64.85% without UC), 6.1% were Black (vs. 10.09% without UC), 3.66% were Hispanic (vs. 12.37% without), and 24.39% were Asian or Pacific Islander (vs 12.79% without). Conclusions: In the population studied, there was a significant correlation between UC and cholangiocarcinoma. Patients with cholangiocarcinoma and UC tended to be younger with fewer comorbidities than their counterparts without. There were nearly double the percentage of Asian patients with cholangiocarcinoma and UC as compared to Asian patients without UC. Understanding the characteristics of patients with UC who develop cholangiocarcinoma is important as it could inform future best practices in potential screening and early detection of carcinomas in patients with UC. Research Sponsor: None. The effect of obesity in hospitalized patients with hepatocellular carcinoma: A nationwide analysis. First Author: Ekrem Turk, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL Background: Obesity, a prominent issue in global health, is known to increase the risk factors associated with a variety of cancers, including hepatocellular carcinoma (HCC), the most common type of primary liver cancer. While existing research affirms the heightened risk of developing HCC in individuals with obesity, there remains a significant gap in understanding the specific influences of obesity on the outcomes of patients admitted with primary HCC diagnosis during their index hospital admission. This study explores the mortality rate, length of stay (LOS), and healthcare utilization in HCC patients with and without obesity. Methods: Nationwide Inpatient Sample (NIS) was queried to determine adult hospitalized patients with a primary diagnosis of HCC using ICD-10 codes. The primary outcome was defined as the effect of obesity on inpatient mortality in those patients. Secondary outcomes included LOS, total hospital charge, health care utilization, ICU admission. We evaluated the baseline characteristics using the t-test and chi-square test. Background: Escalation of treatment from one to two combined immune checkpoint inhibitors (CPI) has dramatically increased objective and clinical response in advanced hepatocellular carcinoma (HCC) patients. Establishing strategies with more than two CPI agents to further increase response while maintaining a manageable toxicity is therefore a top priority. The upfront simultaneous use of three or more CPI can yield a strong initial response to treatment, but it may also increase treatment-related toxicity. An alternative approach, which prioritizes safety over immediate response, involves utilizing different CPI doublets in a sequential manner. However, this design entails switching to a different combination only after radiological progression is observed, and recurrent progressions may lead to deteriorating liver function and treatment resistance. Trials of immunotherapy of HCC conducted in recent years showed that the efficacy of CPI, when used simultaneously, outweighs the drawbacks of their combined toxicity and that early radiological response to treatment, or the lack thereof, is a predictor of clinical outcome. In addition, failure of trials using broad-spectrum tyrosine kinase inhibitors (TKI) and CPI suggest that antibodies or narrow-spectrum TKI should be used for future CPI-based combinations in HCC studies. Based on these considerations, the MON-TBLANC study is the first trial to assess the effectiveness of up-front triple treatment with a combination of the three currently approved immunological agents for HCC and to implement the concept of treatment escalation determined by lack of early radiological response (as opposed to treatment progression

TPS579 Trials in Progress Poster Session

Anlotinib combined with penpulimab and hepatic artery infusion chemotherapy (HAIC) in the first-line treatment of unresectable hepatocellular carcinoma. First Author: Gong-Rang Chen, Yiyang Central Hospital, Yiyang, China

Background: Hepatic arterial infusion chemotherapy (HAIC) is recommended as a treatment option in patients with advanced hepatocellular carcinoma (HCC). Anlotinib plus penpulimab, a humanized anti-PD-1 IgG1 antibody, has shown encouraging activity in the treatment of advanced HCC in an open-label phase II trial (NCT 04172571).

Considering different anti-malignancy mechanisms, combining systemic and locoregional therapies may show a potential synergic effect and promising preliminary efficacy results in advanced HCC. Consequently, the aim of this study is to assess the efficacy and safety of Anlotinib, Penpulimab, plus HAIC for advanced HCC. Methods: Trial design: This single-arm, prospective, phase II study will include treatment-naive adult ($18 years) patients with advanced HCC, ECOG PS 0-2, and Child-Pugh class A-B. A total number of 26 patients will be enrolled for treatment until disease progression or intolerable toxicity. Patients will receive anlotinib (10 mg, p.o., qd, d1-14, q3w), penpulimab (200 mg, i.v., d1, q3w) and HAIC (d1-d2) with the FOLFOX regimen (oxaliplatin 85-130 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil bolus 400 mg/m2 on day 1, and 5fluorouracil infusion 2400 mg/m2 for 48 hours) for 4-6 cycles, followed by maintenance therapy with anlotinib and penpulimab for up to 2 years. The primary endpoint is objective response rate (ORR)), evaluated using RECIST 1.1. Secondary endpoints are median PFS and overall survival (OS), disease control rate (DCR) per RECIST 1.1, quality of life (QOL) and safety. Recruitment for this study will complete in December 2024.

Research Sponsor: None. patients with locally advanced or metastatic FL-HCC or other malignant diseases that carry the DNAJB1-PRKACA fusion transcript. Further, key eligibility criteria include the absence of autoimmune phenomena due to prior immunotherapy agents ($ grade 3) as well as tissue or organ allografts. The FusionVAC-22-based peptide vaccine is applied twice in a 4-weekly interval with the opportunity of a booster vaccination after 11 months. Atezolizumab application starts on day 15 after first vaccination and is continued 4-weekly for 1 year, followed by a 6-month follow-up. The primary objectives of the trial are immunogenicity, in terms of induction of peptide specific T-cell responses until 28 days after second vaccination, as well as safety and toxicity of the peptide vaccine in combination with ICI. Safety assessment is based on the frequency of adverse events according to CTCAE v5.0. Clinical efficacy is determined by iRECIST assessment on imaging. Furthermore, disease control rate, quality of life as well as overall and progression free survival will be assessed. Background: Despite improvements in multidisciplinary healthcare, patients with biliary tract cancer (BTC) have a poor outcome and effective treatment options are limited. Only 20 % of patients are eligible for surgical resection with curative intent, with 5-year overall survival rates , 10 % for all patients. Data on adjuvant chemotherapy alone for BTC are conflicting, and the SOC is treatment with capecitabine according to the UK BILCAP trial, even though BILCAP was formally negative. Based on the positive data for durvalumab in the TOPAZ-1 trial in BTC and for the STRIDE regimen in HCC according to the Himalaya trial data, the evaluation of the IO combination in the adjuvant setting seems promising. Also, the MediTreme trial showed promising response rates in BTC. Preclinical studies indicate that the antibody combination leads to stronger and more durable anti-tumour effects than single therapies, as it synergistically modulates the tumour's immunosuppressive microenvironment, which is particularly pronounced in cholangiocarcinoma. The aim of the ADJUBIL trial is to evaluate the clinical activity of the anti-PD-L1 (programmed-death 1 ligand) antibody durvalumab and the anti-CTLA-4 (cytotoxic T-lymphocyte-associated antigen 4) antibody tremelimumab in combination with or without capecitabine in patients with respectable BTC in the adjuvant setting. This is a randomized phase II study with a pick-the-winner design. The winner of ADJUBIL could be tested against the current SOC capecitabine in a subsequent phase 2/3 trial. Methods: The ADJUBIL trial is an open-label, multicenter phase II study, including patients with BTC after curative surgery (R0/R1) with no previous systemic treatment. Patients are randomized (1:1) to receive either tremelimumab (300 mg, one dose on C1D1) plus durvalumab (1500 mg every 4 weeks; max. 12 months), with or without capecitabine (1250 mg/m 2 twice a day on day 1-14 of 3-weekly cycles; max. 8 cycles). 40 evaluable patients will be enrolled in the study to receive anticancer treatment until disease recurrence or intolerable toxicities. Primary objective is to assess the anti-tumor activity of the treatment in both arms by the recurrencefree survival rate after 12 months. Secondary endpoints are recurrence-free survival, overall survival, toxicity, and quality of life. Exploratory endpoints are to identify predictive biomarkers for recurrence-free survival and overall survival. Study start of the ADJUBIL trial was in June 2021. By September 2023, 15 centers in Germany have been activated and 23 out of 40 planned patients have been enrolled. The first 5 patients in each arm were subject to a safety lead-in phase with close monitoring of (serious) adverse events. The safety assessment revealed no concerns. The study is ongoing. Clinical trial information: NCT05239169. Research Sponsor: None.

TPS580 Trials in Progress Poster Session

TPS584 Trials in Progress Poster Session

Atezolizumab and bevacizumab in combination with TACE for patients with BCLC B HCC. First Author: Stacey Stein, Yale Cancer Center, New Haven, CT Background: The combination of atezolizumab and bevacizumab (AB) is an effective regimen for patients with advanced HCC 1 . Moving effective systemic therapy to earlier stages of HCC is a priority in improving outcomes. Assessing the safety of the combination of AB and TACE is essential to evaluating this regimen. Methods: This is an open-label, single arm pilot study. The primary objective of this study is to examine the safety and tolerability of AB with TACE. The secondary objectives are response rate, time to progression, overall survival, time to TACE progression (TTTP), and time to untaceable progression. Approximately 24 patients will be enrolled. AB will be given every 3 weeks (A: 1200 mg; 15 mg/kg) weeks and TACE will be planned for each patient to be completed in up to 4 treatments. B will be held for cycles that are within 4 weeks before or after each TACE. Imaging will be every 8 weeks for the first year, then every 12 weeks for the second year. Based on data from the GO30140 and the IMbrave 150 studies, we assume the rate of grade 3 or higher AEs is approximately 55% for AB and will likely be higher with the addition of TACE. Safety will be continuously monitored using the Bayesian Predictive Probability (PP) approach 2 . The PP that the rate of grade 3 or higher AEs is related to the combination is greater than 70% by the end of the trial based on toxicity data in the current stage will be continuously updated. The main reasons for exclusion were metastatic disease at presentation (n=128), primary tumor not resected (n=58), and patients not followed at PMCC (n=49) so their surveillance practices cannot be determined from our records. The primary tumor sites were pancreatic (n=50, 57%), appendiceal (n=15, 17%), small bowel (n=11, 13%), rectal (n=10, 12%), and colon (n=1, 1%). Thirty-eight patients (44%) had stage 1 disease, 21 patients (24%) had stage 2, and 28 patients (32%) had stage 3. Forty-six patients (53%) had a WHO tumor grade of 1, 36 patients (41%) had grade 2, and 5 patients (6%) had grade 3. The median duration of follow-up was 18.2 months. Adherence to ordering the recommended surveillance investigations was 23% (20/87). Within the adherent cases, there was a higher number of appendiceal, WHO grade 1, and stage 1 tumors. Sixty-six patients (76%) had at least one test that was not recommended by the guidelines. The most frequent unnecessary tests were CT chest in all patient groups and CT pelvis in pancreatic NETs (Table ). Six patients were lost to follow up and none discharged from surveillance.

Conclusions: Adherence to the CommNETs consensus guidelines was low at our center, suggesting the guidelines had a minor impact on surveillance practices and providing an area for improvement in process of care and resource utilization. Research Sponsor: None.

597 Poster Session

Classification of gastric neuroendocrine tumors and associations with survival. First Author: Yun Song, The University of Texas MD Anderson Cancer Center, Houston, TX Background: The World Health Organization (WHO) classification of gastric body neuroendocrine tumors (GNETs) includes type 1 tumors characterized by hypergastrinemia and arising in a background of atrophic gastritis, type 2 tumors associated with gastrinomas, and type 3 tumors with low serum gastrin level and no background mucosal pathology. However, certain tumors remain unclassified, and the prognostic significance of these tumors is currently unknown. The purpose of this study was to better characterize GNET types and to determine associations with distant metastasis and disease-specific survival (DSS). Methods: Patients diagnosed with GNET (1986 GNET ( -2021) ) were retrospectively identified and tumors classified as type 1, 2, or 3. Unclassified tumors were reviewed for background gastric mucosal changes associated with chronic proton pump inhibitor (PPI) use. Tumors were categorized as PPI-associated if there were prominent parietal and neuroendocrine cell hyperplasia in the background mucosa, in the absence of a gastrinoma and a positive history of chronic PPI use. WHO grade was determined using mitotic index or Ki-67 proliferative index when available.

TPS602 Trials in Progress Poster Session

Phase 1/2 trial of vesicular stomatitis virus expressing human interferon-b and NIS (VSV-IFNb-NIS), with ipilimumab and nivolumab, in patients with neuroendocrine carcinoma. First Author: Patrick Walsh McGarrah, Mayo Clinic, Rochester, MN Background: Poorly differentiated neuroendocrine carcinoma (NEC) is an aggressive malignancy comprising both pulmonary and extrapulmonary primary sites. NEC includes both small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC), as well as other neuroendocrine carcinomas arising from any primary organ. A substantial portion (~40%) of NEC arises from gastrointestinal primary sites. The optimal systemic therapy beyond first line platinum and etoposide is not established. There is a critical need to improve upon the median survival in the second line, as most patients do not survive more than 6 months. The efficacy of dual immune checkpoint inhibitor (ICIs) therapy in NEC shows some promise, but most tumors do not respond. One possible explanation for this is that the tumor microenvironment in NEC is non-inflamed. VSV-IFNb-NIS is a vesicular stomatitis virus (VSV)-based oncolytic virus being tested in multiple early phase clinical trials. Preliminary studies of immune responses in patients receiving VSV-IFNb-NIS therapy suggest some patients develop T cell responses to viral antigens and known tumor antigens. We hypothesize that VSV-IFNb-NIS therapy may convert a non-inflamed or immune-excluded phenotype in NEC to a highly inflamed phenotype that sensitizes the tumor to ICIs. Methods: This is a phase 1-2 safety run-in study designed to determine the safety and efficacy of VSV-IFNb-NIS in combination with dual ICI therapy, ipilimumab and nivolumab, followed by dose expansion in patients with refractory non-small cell lung cancer (NSCLC) or NEC. After a safety run-in, we will be testing the recommended phase 2 dose (RP2D) of VSV-IFNb-NIS in an expansion cohort of patients with SCLC or NEC of any primary site. Patients must have previously progressed on at least one line of systemic therapy. Prior treatment with checkpoint inhibitors is permitted. Patients are treated with ipilimumab and nivolumab on day 1, followed by one RP2D of 1.0x10^11 TCID50 VSV-IFNb-NIS on day 4, followed by nivolumab every 3 weeks and ipilimumab every 6 weeks until progression, up to 2 years. Background: The National Cancer Database (NCDB) is commonly used for analyzing survival outcomes in pancreatic cancer and has a robust number of patient-specific socioeconomic variables. Although these aggregated variables are commonly collected, their utility and impact on survival has infrequently been assessed. We aim to assess the distribution of income and education variables on their impact on survival models for patients who underwent resection for pancreatic ductal adenocarcinoma (PDAC). Methods: Patients undergoing definitive surgery for PDAC between 2004-2020 were identified from the NCDB. Variables of interest were income and education according to the patient's ZIP code of residence.

608 Poster Session

Patient factors and survival outcomes of pancreatic signet cell carcinoma: A comprehensive review and analysis. First Author: Aron Lee, Creighton University School of Medicine, Omaha, NE Background: Pancreatic signet cell carcinoma is an aggressive, rare subtype of pancreatic adenocarcinoma that constitutes less than 1% of all pancreatic cancers. This subtype can manifest as solitary cells or a cluster within the background of pancreatitis, often leading to an incorrect diagnosis during biopsies. The rarity and challenges associated with its diagnosis significantly impact its poor prognosis. With an average age of diagnosis of 67.3 years and a median life expectancy of 12.6 months, there exists a lack of information on the disparities that exist in these patients and how patient demographics contribute to differences in survival outcomes. Methods: We used the National Cancer Database to identify patients diagnosed with pancreatic signet ring cell carcinoma (ICD-O-3 histology code 8490) between 2004-2019 (N=1746

PANCREATIC CANCER 151s

Improving timeliness and equity in germline genetic testing for pancreatic ductal adenocarcinoma patients: A comparative analysis and future strategies. First Author: Xianghui Zou, Department of Internal Medicine, North Shore University Hospital & Long Island Jewish Medical Center, New Hyde Park, NY Background: Germline genetic testing is recommended for patients with pancreatic ductal adenocarcinoma (PDAC). Our previous study identified delays in germline testing for socioeconomically disadvantaged patients. We aimed to compare delays before and after implementing recommendations for same-day germline testing and identify reasons why germline testing was not performed. Methods: Using an IRB-approved protocol, PDAC patients were identified from Jan 2022 to Dec 2022 in our EMR system. Median income was estimated by zip code. Delays were calculated as the difference between diagnosis and germline test date. Social work needs were assessed through EMR review.

An in-depth chart review was conducted to identify why tests were not performed.

Results: An additional 100 patients were found with tests performed. Compared to our previous 135-patient study with a median delay of 27 days (d) in testing, our recent data showed a median delay of 15d (p=0.0215). In our previous study, 50 out of 135 patients (37%) received testing within two weeks of their PDAC diagnosis, whereas our recent data showed that 49 out of 100 patients (49%) received testing within two weeks (c 2 =3.372, p=0.0663), a 32% relative increase. The negative correlation between median income and delays in testing (r=-0.2578, p=0.0025) found in our previous study no longer existed in our recent analysis (r=0.0419, p=0.6802). Compared to our previous study in underserved minority (UM) patients (African American and Hispanic), our recent data showed a significant decrease in the delays for testing in UM patients (66d vs 19d, p=0.0041). We did not identify a difference in delays for testing between UM and not UM patients in the recent dataset (UM: 19d vs not UM: 15d, p=0.8075). In addition, compared to our previous study in patients with social work (SW) needs, our recent data showed a significant decrease in the delays for patients with SW needs (104d vs 13d, p=0.0004). We did not detect a significant difference between patients with SW needs and without SW needs in our recent data (SW: 13d vs no SW: 15d, p=0.8041). Finally, in our analysis of 87 patients without documented tests, 51 (59%) received care elsewhere, 25 (29%) were never offered tests, 5 (6%) refused tests, and 6 (7%) pursued a palliative approach. Conclusions: Our recent analysis showed a significant decrease in delays of testing, as more patients received prompt testing after PDAC diagnosis. Socioeconomically disadvantaged patients and those with social work needs no longer experienced significant delays in testing. To further mitigate delays, we plan to initiate germline testing during the first visit by providing introductory videos to increase understanding of consent. Furthermore, the substantial number of patients who were not offered tests will raise physician awareness regarding the necessity of offering germline tests. Research Sponsor: None.

612 Poster Session

Assessing disparities in pancreatic cancer outcomes in African Americans.

First Author: Shiva Shrotriya, Corewell Health William Beaumont University Hospital, Royal Oak, MI Background: Pancreatic Adenocarcinoma (PA) is a leading cause of cancer-related death across the world, with poorer outcomes noted in minority populations. The observed variation in outcomes has been attributed to delayed diagnosis, barriers to optimal treatment and health care related disparities. We evaluated the impact of race on clinical presentation and outcomes in pancreatic cancer at a large academic teaching center. Methods: We performed a retrospective review of patients with pancreatic adenocarcinoma diagnosed between January 2016 to December 2021.

613 Poster Session

A novel early cancer detection approach for pancreatic cancer. First Author: Maarten F. Bijlsma, Amsterdam UMC, University of Amsterdam, Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Oncode Institute, Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, Netherlands Background: Pancreatic adenocarcinoma (PDAC) is commonly diagnosed at advanced stages, leading to high mortality rates. Earlier detection of PDAC is associated with improved long-term survival, but effective population-level screening is not available.

There is therefore an urgent need to improve early detection of PDAC. Wholomics has developed a PDAC-specific proprietary early detection test, using cancer-specific molecular signatures in peripheral blood. Methods: We conducted a retrospective analysis of serum samples from the Amsterdam UMC Liquid Biopsy Center. Three cohorts were included in this study: 1) A cohort of healthy control subjects, 2) patients with a histopathologically confirmed diagnosis of PDAC spanning stages I through IV, and 3) patients with a confirmed diagnosis of chronic pancreatitis. Peripheral blood samples of cancer patients were taken before treatment or surgery. Wholomics used its proprietary technology to quantitatively analyse all serum specimens. Disease-specific molecular signatures were identified and used to develop computational biomarkers specific to both pancreatic pathologies (chronic pancreatitis and pancreatic cancer) and to pancreatic cancer individually. A comparative analysis was conducted employing multiple machine learning algorithms, which were subjected to a 10-fold cross-validation procedure.

617 Poster Session

Amplified Sciences PanCyst Pro Panel to accurately identify non-mucinous pancreatic cyst fluid. First Author: Mini Thomas, Amplified Sciences, West Lafayette, IN Background: Pancreatic cysts are rarely symptomatic, and, consequently, are detected incidentally during routine imaging analyses for unrelated disorders. Guidelines for diagnosis of pancreatic cysts rely on imaging and supportive analyses of fluid extracted during endoscopic ultrasound with fine-needle aspiration (EUS-FNA). Unfortunately, currently available protein markers and assays are not sufficiently accurate to rule-out patients in whom a non-mucinous pancreatic cyst has formed. Since non-mucinous pancreatic cysts seldom progress to cancer, this patient population is at risk of being subjected to the severe physical, emotional, and financial burdens associated with unwarranted surveillance, testing, and possible surgical intervention. Furthermore, identification of mucinous pancreatic cysts does not establish the risk of progression to cancer (rule-in) or the need for surgical intervention. Methods: To address the unmet needs in pancreatic cyst diagnosis, Amplified Sciences has combined a panel of markers with a clinically translated surface enhanced Raman spectroscopy (SERS)-based protease activity assay as a rule-out diagnostic tool. The tri-analyte panel was tested on a cohort of 185 retrospective samples gathered from three separate institutions (UPMC, IU Health, and UCSF) and consumed only 12 mL of cyst fluid per sample.

The goals of this study were to establish the negative predictive value (NPV) of this panel prior to translation to a CLIA-regulated laboratory and create a preliminary algorithm for analysis. Results: The results of this statistically powered study show that protease activity outperforms carcinoembryonic antigen (CEA), a current standard diagnostic marker for pancreatic cyst fluid, in sensitivity, specificity, and NPV. Furthermore, in combination, the tri-analyte panel identifies non-mucinous pancreatic cysts with 99% sensitivity and a negative predictive value .95%. Conclusions: These results support the use of this panel in clinical settings as a diagnostic tool to rule-out patients from surgical intervention, as well as the use of SERS as an optical detection mode for clinical diagnostics. Future work will continue to address the unmet need for improved diagnostic information through multiplexed analyses of markers that consume comparatively minimal volume of pancreatic cyst fluid samples. Studies will also seek to build on the SERS platform by introducing more dyes, substrates, assays, and analytical methods. Amplified Sciences would like to acknowledge significant efforts to build the clinical samples cohort from Gina Zhu, Kelli Ifuku, and Dr. Kimberly Kirkwood from USCF, Christine Decapite and Dr. Randall Brand from UPMC, and Michele Yip-Schneider and Dr. C. Max Schmidt from IU Health. Research Sponsor: Amplified Sciences.

618 Poster Session

Pancreatic biopsy evaluation with nsCanary: A "smart ROSE" device for feedback on sample adequacy and cancer presence in endoscopic biopsies-Initial human clinical trial results. First Author: Les Bogdanowicz, NovaScan, Chicago, IL Background: Pancreatic cancer (PC) accounts for 0.5 million new cases and 4.7% of the world's cancerrelated deaths in 2020. Endoscopic ultrasound (EUS) guided fine needle biopsies (FNB) are the current standard of care for confirming suspicious lesions, however the diagnostic accuracy is reported below 70%. Rapid on-site evaluation (ROSE) improves the diagnostic performances of biopsies to reduce the number of needle passes, complication rates, and the need for additional procedures. However, availability of an on-site pathologist is often not feasible. NovaScan has pioneered the use of an impedance spectroscopy biomarker for cancer detection in different tissues based on the Cole Relaxation Frequency (CRF). NovaScan has developed the nsCanary, a "smart ROSE" device that assesses PC presence in FNBs obtained during endoscopic procedures ex vivo, in real-time and on-site, without altering the tissue sample or affecting the workflow. Methods: Data were collected in a double-blind, IRB approved study from a cohort of 53 patients (28 males, 25 females) undergoing EUS procedures for suspected pancreatic lesions at the Texas International Endoscopy Center. FNBs were performed with a 22 gauge biopsy from a transduodenal approach. Each biopsy sample was transferred onto a disposable strainer allowing for any excess fluid to drain. An electrode for scanning was placed onto the core samples for data collection with the nsCanary a low cost, portable device used in the operating room. CRF is measured in the 1 kHz -10 MHz frequency range via custom-designed hardware and assessment of the sample is completed in a few seconds. Subsequently, the sample is flushed into a pathology jar to undergo the standard workflow for cytology. The algorithm for extracting the CRF from the measurement was developed based on our previous preclinical study with transgenic KPC mice Samples with a CRF below 1 MHz were considered noncancerous, while CRF values above 1MHz or the absence of a CRF reading were considered cancerous. Results: PC assessment provided by nsCanary was validated against pathology outcomes for each biopsy sample. Findings showing a sensitivity of 86.7% and a specificity of 84.2% are reported in the table. Conclusions: We believe the nsCanary device will provide immediate feedback to the endoscopist on cancer presence and on the adequacy of the sample. This device is intended to support the decision-making process, by enabling clinicians to overcome the challenge of proving cancer presence during the first biopsy procedure, ultimately avoiding revisits and unnecessary trauma. Research Sponsor: None.

Confusion matrix for nsCanary assessments and pathology outcomes.

PANCREATIC CANCER 153s

622 Poster Session

Optimising utility of selective internal radiation therapy in metastatic pancreatic adenocarcinoma. First Author: Prasad Cooray, Yarra Oncology, Melbourne, Australia Background: Selective internal radiation therapy (SIRT) using Yttrium-90 containing microspheres has established benefit for a number of cancers but there is limited data available on the utility of SIRT for the treatment of metastatic pancreatic ductal adenocarcinoma (PDAC). Methods: In this retrospective audit we identified 32 patients who received SIRT using Yttrium-90 microspheres for metastatic PDAC in 2 treatment centres. All patients received SIRT in combination with chemotherapy. Data was analysed from electronic medical records. Results: Thirty two patients with metastatic PDAC who had SIRT were identified. Patients received SIRT (median activity 1.6 GBq) in combination with chemotherapy (platinum-based; n = 23, non-platinum-based; n = 9) . Three patients remain alive and 29 patients were included in the survival analysis. For the entire group, the median OS was 15 months (range 4-49), median survival from time of SIRT was 9 months (range 1-48) and median PFS from time of SIRT was 4 months (range 1-25). Median PFS (6 vs 2 months, p=0.0011) and OS (13 vs 4 months, p=0.0004) from SIRT was significantly better when SIRT was given with 1st-line therapy vs with 2nd-line and beyond. Median PFS from SIRT was significantly better (10 vs 2 months, p=0.0020) when combined with 1st line platinum-based chemotherapy (n=14) vs nonplatinum based treatment (n=6). 18 month survival was 40% (n=13) with 9/13 patients having had SIRT with 1st line with platinum-based therapy. 24 month survival was 22% (n=7) with 7/7 patients having had SIRT with 1st line with platinum-based therapy. SIRT was well-tolerated with no associated 30-day all-cause mortality. Grade 3 adverse events were liver abscess (7%, n = 2), gastritis (7%, n = 2) and duodenitis (7%, n=2

628 Poster Session

De-escalation and dose density in real-world patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who received FOLFIRINOX in the first line. First Author: Syvart Dennen, Genesis Research, Hoboken, NJ Background: FOLFIRINOX (FFX) is a recommended first-line (1L) treatment for patients (pts) with mPDAC and good performance status but is known for high toxicity. To make the regimen more tolerable for pts, clinicians may omit components and/or reduce doses (referred to as "de-escalation"). To better understand the frequency and degree of deescalation in outpatient clinical practice, we examined real-world (RW) treatment patterns among mPDAC pts receiving FFX in 1L. Methods: This retrospective observational study utilized the Ontada Clinical Data View: Pancreatic Cancer database. Adult pts diagnosed with mPDAC between November 2018 and November 2022 who initiated treatment with FFX in 1L within 90 days of their diagnosis for metastatic disease were included in the study. Receipt of FFX was defined as receiving all four regimen components within 28 days of 1L initiation. Modified FFX (mFFX) was defined as administration of ,150mg/ m 2 of irinotecan or ,2,720mg/m 2 5-FU total (bolus + infusion) during cycle 1. 6-week dose density was defined as the actual dose received of each component in the 6 weeks following treatment initiation as a percent of the expected dose over 3 two-week cycles [expected FFX dose defined as 2800 mg/m 2 of 5-FU (bolus + infusion), 400 mg/m 2 of leucovorin, 180 mg/m 2 of irinotecan, and 85 mg/m 2 of oxaliplatin per cycle].

Results: 1,215 mPDAC pts met the study inclusion criteria, with .99% receiving mFFX.

The median age at 1L initiation was 65yr (IQR: 58-71), 57% were male, 68% were white, 15% had an ECOG score of 0, 39% had an ECOG score of 1, and 6% had an ECOG of 2. The median number of FFX cycles was 5 (IQR: 2-9). In the first administration, 97%

629 Poster Session

Real-world overall survival and time to next treatment in patients with metastatic pancreatic ductal adenocarcinoma who received FOLFIRINOX and modified FOLFIRINOX in the first line. First Author: Syvart Dennen, Genesis Research, Hoboken, NJ Background: FOLFIRINOX (FFX) is a recommended first line (1L) treatment option for patients (pts) with mPDAC but is known for its high toxicity. Efforts to balance pts' quality of life (QoL) during treatment with treatment effectiveness have led to the use of modified FOLFIRNOX (mFFX) regimens that employ decreased doses of FFX components. Further evidence is needed to assess OS and progression-free survival (PFS) among pts who receive FFX or mFFX treatment in the real world compared to the trial setting. We identified a realworld (RW) sample of pts with mPDAC treated with FFX and mFFX in 1L and assessed their OS, and, as a RW proxy for PFS, TTNT. Methods: This retrospective observational study utilized the Flatiron Metastatic Pancreatic Cancer Enhanced Data Mart. Adult pts diagnosed with mPDAC between January 2014 and May 2022 who initiated treatment with FFX or mFFX in 1L within 90 days of their diagnosis for metastatic disease were included in the study. mFFX was defined as administration of ,150mg/m 2 of irinotecan or ,2,720mg/m 2 5-FU total (bolus+infusion) during cycle 1; doses greater than these were considered FFX.

TTNT was defined as duration between 1L treatment initiation and the start of second line therapy or death. Kaplan-Meier analyses were used to assess median OS and TTNT from the start of 1L FFX or mFFX treatment and log-rank tests for the statistical significance of differences in OS and TTNT. Results: 2,212 mPDAC pts met the study inclusion criteria, with 507 pts (23%) receiving FFX and 1,705 pts (77%) receiving mFFX in 1L. For FFX vs. mFFX, the median age at 1L initiation was 63yr vs. 65yr, 72% vs. 56% were male, 67% vs. 63% were white, 36% vs. 30% had an ECOG score of 0, 31% vs. 32% had an ECOG score of 1, and 83% vs. 81% received treatment at community oncology centers. For FFX vs. mFFX, median OS was 9.5 (95% CI: 8.9-10.7) vs. 9.0 months (95% CI: 8.4-9.7) (p=.452) and median TTNT was 4.8 (95% CI: 4.5-5.5) vs. 4.8 months (95% CI: 4.5-5.2) (p=.256). Conclusions: In a RW sample of 2,212 pts receiving 1L FFX and mFFX at primarily community oncology practices in the United States from 2014-2022, more than three-quarters received mFFX. Pts experienced similar median OS and TTNT across the two regimens, indicating that full-strength FFX may provide little benefit to OS in exchange for its increased toxicity. In the PRODIGE 4/ACCORD 11 trial of unmodified FFX, conducted earlier (2005 FFX, conducted earlier ( -2009) ) among a group of 342 French pts, median OS was 11.1 months (95% CI: 9.0-13.1) and median PFS was 6.4 months (95% CI: 5.5-7.2). The median RW OS of FFX and mFFX pts in our study was numerically lower than the trial, as was RW TTNT compared with trial PFS. Future research should seek to understand the factors driving differences in RW and clinical trial outcomes as well as to assess the tradeoff between regimen toxicity and survival benefit. Research Sponsor: Ipsen Biopharmaceuticals, Inc.

630 Poster Session

Clinical outcomes and molecular characteristics of patients with pancreatic acinar cell carcinoma. NextGen DNA sequencing (NextSeq, 592 genes and NovaSeq, WES) and IHC were analyzed. Immune cell fraction was calculated by QuantiSeq. Overall survival (OS) analysis (time of tissue collection to last contact) was obtained from insurance claims and calculated with KM method. Statistical significance was determined using Chi-square/Fisher-Exact and adjusted for multiple comparisons (q,0.05). Results: No age or sex differences were seen between PDAC (median 68yo) and PASC (median 68.5yo), however PSCC was more prevalent in younger pts (median 62.5yo, q,0.05). Mutation rates of CDKN1B (3% vs 0.2%), SF3B1 (8 vs 2%), PTEN (5 vs 0.8%), BCL9 (4 vs 0.4%), AXIN1 (4 vs 0.2%) and CASP8 (3 vs 0.2%) and amplifications of AKT2 (5 vs 2%), ZNF384 (1 VS 0.1%), HMGA2 (7 vs 0.7%) and ROS1 fusions (1 vs 0.04%) all trended higher in PASC than PDAC (p,0.05). Several YAP signaling and squamous differentiation genes were significantly differentially expressed among histologies (table ). PD-L1 IHC was higher in PASC vs PDAC (37 vs 14%, q,0.05); with a trend towards higher MSI-H (6 vs 1%) & TMB-H (6 vs 2%) in PASC vs PDAC (p,0.05). Higher infiltration of CD4 + T cells into the TME was seen in PASC vs PDAC (non-zero %, 73% vs 23%, q,0.05). Several immune genes (CD274, IDO1, LAG3, & CTLA4) had higher expression in PASC vs PDAC (fold change 1.3-3.1, q,0.05). The MAP kinase pathway activation score (MPAS) was lower in PASC vs PDAC (median score -0.48 vs 0.25), while the IFN gamma signature was higher in PASC vs PDAC (median -0.24 vs -0.33) [both q,0.05]. There was increased OS for PASC compared to PSCC (12.6 vs 4.7 mo, HR=0.43, CI=0.25-0.75, p=0.002); no significant difference in OS was observed between PASC and PDAC. Conclusions: This is the largest molecular profiling analysis of PASC, which is characterized by unique genomic alterations, and is associated with higher PD-L1 expression, immune related gene expression, CD4+ T cell infiltration and IFN gamma signature, and lower MAPK activation. PASC is associated with better OS compared to PSCC. These findings may provide subtype-specific therapeutic opportunities for PASC and PSCC pts. Research Sponsor: None. Multivariate analysis revealed that 949.7 U/mL of CA19-9 was an independent risk factor for RFS and OS in these patients (P = 0.010 and = P = 0.001, respectively), along with lymph node metastasis( P = 0.017 and P = 0.008), unlike the median CA19-9 level (P = 0.210 and P = 0.150). Conclusions: The results of this study demonstrate that preoperative 949.7 U/mL $ CA19-9 may be associate with poor prognosis in PDAC. In summary, our study demonstrated, for the first time, that the adjusted cutoff value of CA19-9 was an important biomarker for the prediction of recurrence and prognosis in patients with resected PDAC. Patients with high levels of CA19-9 before surgery had a higher risk of recurrence and poorer prognosis than those with low levels of CA19-9, therefore they may have benefitted more from drug treatment than surgical intervention. 8 [4.7-53.4 ], p , 0.001). Correlation of +ctDNA with recurrence showed a sensitivity of 52% (10/19), specificity of 100% (14/14), PPV of 100% (10/10) and NPV of 61% (14/23). Our institutional data were then combined with 138 pts reported in 3 prior publications/ abstracts, for a total of 171 pts. Median follow-up ranged from 11.9-14.3 months and the overall EOT+ rate was 39% in the pooled cohort. The pooled sensitivity was 67% (49/73), specificity was 83% (81/98), PPV was 74% (49/66) and NPV was 77% (81/105). In each study as well as the pooled analysis, an EOT+ ctDNA was associated with significantly shorter RFS (HR = 8.1-120.5). Among 10 pts at our institution with recurrence, a + ctDNA test was detected after the recurrence 90% of the time, with a median lag-time of 4.70 months after recurrence (range -2.2 to 16.67 months). In the pooled cohort, among the 73 pts with recurrences, the ctDNA test was + before, at the time of, or after the recurrence in 23 (32%), 9 (12%) and 17 (23%) pts respectively; the ctDNA was negative despite recurrence in the remaining 24 (33%) pts. Conclusions: A tumor-informed positive ctDNA test after EOT shows high specificity and PPV for recurrence and is associated with significantly worse RFS in the MRD setting, while sensitivity of the test remains low. When positive, ctDNA assessment provides an opportunity for innovative therapies in the adjuvant setting to improve outcomes for localized PDAC. Research Sponsor: None.

696 Poster Session

Predictive multi-omics analysis of BPM31510 in combination with gemcitabine in a phase 2 study of advanced pancreatic ductal adenocarcinoma (PDAC). First Author: Madappa N. Kundranda, Banner MD Anderson Cancer Center, Gilbert, AZ Background: Advanced PDAC has limited therapeutic options. BPM31510-IV, a novel nano formulation of Ubidecarenone was evaluated in Phase 2 in patients with advanced PDAC. In addition to response and safety, the study included FDG-PET and omics as exploratory analyses. Multi-omics analyses from longitudinally collected patient samples including a subset of Adequately Treated Analysis Set (ATAS) (n=19) were performed to determine potential biomarkers associated with clinical outcomes. Methods: Metastatic PDAC patients (N=45) who had previously received between one and three lines of prior therapy were enrolled in this study. Omics analyses including proteomic, structural lipidomic, signaling lipidomic, and metabolomic measurements were performed on patient buffy coat and plasma samples. Biomolecules with significant association to patient outcome (PFS, OS & TTP) were identified by linear regression analysis. Additional analysis with mixed effect linear modeling approach was used to relate omic values during ten weeks of treatment and patient ATAS status and time on study. Previous analysis of proteomics from patients in a phase 1 solid tumor study was mapped onto a similar omics output for phase 2 to reveal predictive biomarkers for disease status.

Results: Proteomics analysis on patient buffy coats revealed enrichment of dicarboxylic and tricarboxylic metabolic processes, mitochondrial membrane space proteins, pyruvate metabolism, and malate/aspartate shuttle pathway with a positive correlation with TTP in the model, demonstrating an integrated connectivity to Ubidecarenone's functional effects on metabolism. Medium chain acyl carnitines and c-reactive protein (CRP) were identified as having the most significant differences in trajectories between patient ATC status by mixed effect linear modeling. Medium chain acyl carnitines differences could likely be the result of an integrated adaptation of liver homeostasis and physiological activity impacted by treatment. Analysis of RECIST1.1 evaluated in Phase 1 clinical trial and subsequently validated in Phase 2 trial identified 4 proteins with predictive utility at the start of treatment (t=0) (SERPINA5, Vitronectin, Lumican, Proteosome 20S subunit alpha 4), 5 lipid molecular species, and 1 metabolite (2-keto-isovalerate). ) were calculated by averaging the positive z scores of activators and negative z scores of repressors in the myostatin-activin pathway. Activators were ACVR1B, ACVR1C, ACVR2A, ACVR2B, SMAD2, SMAD3, SMAD4, and TGFBR1, while repressors were SMAD1, SMAD5, SMAD6, SMAD7, SMURF1, and SMURF2. The top quartile (Q4) and bottom quartile (Q1) of GS were compared using chi-squared and Fisher-Exact tests. RNA deconvolution analysis with QuantiSEQ estimated cell infiltration in the tumor microenvironment (TME). Differences in overall survival (OS) were analyzed from insurance claims data and calculated from time of tissue collection using Kaplan-Meier estimates. Statistical significance was determined as a P-value adjusted for multiple comparisons (q,0.05). Results: GS were higher in primary tumors compared to metastases (median: -0.71 vs -0.86, q,0.05). GS was associated with increased PD-L1 IHC expression (Q1 21.2% vs Q4 10.3%, q,0.001), but not TMB-high (1.9% vs 2.1%, q=1) or MSI-H status (1.1% vs 1.3%, q=1). GS correlated with increased expression of immune related genes (CD274, CD80, IDO1, CD86, PDCD1, LAG3, CTLA4, HAVCR2, and IFNG, q,0.05). However, TME immune cell infiltration did not vary based on cachexia GS. Mutation rates of TP53 (Q1 79.4% vs Q4 73.7%), ARID1A (Q1 11.8% vs Q4 6.9%) and KRAS (Q1 92.7% vs Q4 86.4%) were associated with Q1-GS (all q,0.01), while STK11 mutations (1.1% vs 3.0%, q=0.001) were associated with Q4-GS. Spearman correlation linked cachexia GS with the lipid metabolizing genes UCP2 (rho=0.49) and UCP3 (rho=0.30), as well as the inflammatory markers CCL2/MCP-1(rho=0.34) and IL1B (rho=0.33). Decreased OS was seen with higher tumor expression of the myostatin-activin pathway activator, SMAD3 (6.6 vs 8.5 mo, HR=1.22, CI 1.12-1.33, P,0.001), and lower expression of the repressor SMAD7 (6.9 vs 8.9 mo, HR=0.91, CI 0.79-0.90, P=0.034) in metastatic PDAC. Conclusions: This is the largest molecular and clinical characterization of the myostatin-activin cachexia pathway in PDAC. Our data show that increased activation of the myostatin-activin pathway is associated with immune mediators, lipid metabolism, and inflammatory gene activation. Activators and repressors are significant predictors of survival in PDAC, suggesting possible novel therapeutic targets. Research Sponsor: None.

700 Poster Session

Inter-reader variability of imaging biomarkers for therapeutic response in pancreatic ductal adenocarcinoma. First Author: Jon Stanley Heiselman, Memorial Sloan Kettering Cancer Center, New York, NY

Background: Indeterminate borders of pancreatic ductal adenocarcinoma (PDAC) can impair reliability of lesion annotation in imaging assessment of therapeutic response (TR) after neoadjuvant chemotherapy (NAT). Previous work showed that longitudinal image registration algorithms can track treatment-related changes and produce quantitative imaging biomarkers (QIB) for TR that predict overall (OS) and recurrence-free survival (RFS). We compare interreader agreements of these biomarkers against conventional RECIST and tumor volume QIB. Methods: N=30 patients enrolled in a Phase II clinical trial comparing outcomes of a NAT regimen were retrospectively analyzed. In baseline and restaging CT, whole pancreas and tumor segmentations and tumor diameters were annotated by 2 expert attending radiologists and 2 novice radiology fellows. For each reader, percent change in tumor diameter (RECIST score), percent change in tumor volume (DV), and difference in ratio of tumor burden to pancreas volume (DB) were computed as QIB for TR across the NAT interval via two approaches: image registration of the baseline tumor region of interest, and direct segmentation of the PDAC lesion in baseline and restaging images. Inter-reader agreements of RECIST, DV, and DB QIB from both approaches were compared via concordance correlation coefficient (CCC). Associations with OS and RFS were compared over 5-year follow-up via Harrell's C-index. Results: Association of longitudinal changes of genomic alteration of circulating tumor DNA with treatment response in pancreatic cancer. First Author: Jin Ho Choi, Samsung Medical Center, Seoul, South Korea Background: Recently, the evaluation of circulating tumor DNA (ctDNA) in pancreatic cancer (PC) patients has gained attention for detection of mutation profile. However, the concordance between tissue next-generation sequencing (NGS) and ctDNA NGS remains unclear. Additionally, the dynamics of genomic alterations during treatment or disease progression are not well understood. Methods: In this prospective cohort study conducted at Seoul National University Hospital from Jan 2022, tissue samples from endoscopic ultrasound-guided fine needle biopsies and blood samples were collected from PC patients. Genomic DNA from the treatment naïve primary tissue and ctDNA from the blood obtained before any treatment and during follow-up with anti-cancer treatment were obtained. Genomic alternation was analyzed based on targeted NGS based panel deep sequencing including 41 genes. Results: The concordance of genomic alteration profiles between tissue NGS and ctDNA NGS was evaluated in 55 patients, and the mutation detection rate of patients who were diagnosed as stage I or II disease were 100% (14 of 14) in tissue NGS and 86% (12 of 14) in ctDNA NGS. That of patients who were diagnosed as stage III or IV disease was 92.7% in tissue NGS (38 of 41) and 90% (37 of 41) in blood ctDNA NGS. Among the study patients, the longitudinal changes of genomic mutation profile were evaluated in the patients at the first treatment response assessment, and patients with progressive disease showed significantly greater amounts of mutations including newly detected Tier1/2 variants than baseline and the previous response assessment. Conclusions: In conclusion, there is comparable mutation detection between tissue genomic DNA and blood ctDNA. The significant increase in ctDNA mutations during disease progression suggests their association with immune evasion and cancer evolution. Further studies utilizing our prospective cohort are needed to explore clinical implications of these results. Research Sponsor: None.

702 Poster Session

Clinical and prognostic characteristics of early onset metastatic pancreatic cancer. First Author: Andrea Pretta, Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy Background: In the last decade several studies have shown an increase in the incidence of early-onset PDAC (EO-PDAC), conventionally defined as cancer that occurs in adults between the ages of 18 and 49. Clinical and prognostic data on this setting are limited and conflicting. The aim of our study was to evaluate the clinical, and prognostic differences in a large group of patients with early onset mPDAC. Methods: We retrospectively collected data from 368 patients affected with metastatic pancreatic ductal adenocarcinoma, from 3 different Italian Institutions. All patients had one or more metastatic sites, and received first-line chemotherapy. The main objective of the study was to evaluate the median overall survival in EO-PDAC patients compared to late onset PDAC (LO-PDAC), while secondary endpoint was evaluations of mPFS. Statistical analysis was performed with the MedCalc package. Results: 30 (8,1%) patients were early onset and 338 (91,9%) were late onset; median age was 46 (65) and 68 (68), respectively. M/F ratios were 1:1 in both group. In the overall population mOS was significantly lower in EO-PDAC patients: 10,0 versus 15,0 months (p = 0,03). Furthermore, mPFS was significantly lower in EO-PDAC patients: 5,0 versus 8,0 months (p = 0,04). ORR obtained from 244 pts were: 11% in EO-PDAC and 24,7% in LO-PDAC.

Conclusions: The results of our work, although limited by the retrospective nature of the study, showed a worse prognosis for patients with early onset PDAC compared to late onsets. Further investigations will be needed to better understand this growing group of patients from a molecular and therapeutic point of view. Research Sponsor: None.

703 Poster Session

The effect of germline DNA repair mutations on radiosensitivity in pancreatic ductal adenocarcinoma. First Author: John Michael Bryant, Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL Background: The association between homologous recombination deficiency (HRD) in pancreatic ductal adenocarcinoma (PDAC) and sensitivity to platinum-based chemotherapy highlights the need to further understand how germline DNA repair mutations influence the efficacy of different therapies. Given the recent ALLIANCE data that chemotherapy alone is an acceptable standard of care to enhance R0 resection, the focus has shifted towards the contribution of radiotherapy. However, the relationship between germline DNA repair mutations in general and radiosensitivity remains less understood. This study explores the relationship between germline mutations and the Radiosensitivity Index (RSI) gene signature. Methods: After obtaining institutional review board approval, a retrospective analysis was performed of patients who had both RSI and germline mutation testing (i.e., BRCA1, BRCA2, BLM, ATM, MLH1, MSH2, MSH6, PMS2, and BARD mutations) between 1999 and 2023 at a single institution. Student T, Chi squared, Kaplan Meier (KM), Cox univariate log regression (UVA), and Mann-Whitney U (MWU) tests were used for statistical analyses. Results: A total of 25 patients were included, 13 with mutations and 12 without. MWU analysis demonstrated a significant difference in RSI values, where patients with mutations exhibited greater radiosensitivity (mean 0.379 vs. 0.464, p=0.040). The median age at diagnosis, max diameter of tumor, and baseline CA 19-9 were 67 years (range 47 -77), 3.4 cm (range 0.8 -8.2), and 288 (9.5 -26,100), respectively. Most of the tumors were resectable (84%), stage IIB (36%), and grade 2 (68%). All patients underwent resection, with the majority without neoadjuvant therapy (96%). Most patients received chemotherapy (n=18; 72%), most commonly gemcitabine monotherapy (n=14/18). A majority also received radiation therapy (n=15; 60%), with 93% receiving chemoradiation (n=14/15). The median follow-up was 20.8 months. KM analysis yielded a median overall survival (OS) of 20.0 months (95% CI: 7.1-33.0) and progression-free survival (PFS) of 15.1 months (95% CI: 12.3-18.0) for the entire cohort. At the time of analysis, 15.4% of patients with mutations were alive (.10 years), compared to none without mutations (p=0.157). There were no statistically significant differences between the two cohorts for clinical outcomes on KM analysis. On UVA, worse OS was correlated with stage III (HR 7.9, 95% CI 1.2 -50.2) and IV (HR 11.8, . No other variables were associated with OS on UVA or on mutant-only subgroup analysis. Conclusions: Our findings demonstrate an increased radiosensitivity in patients with germline DNA repair mutations, suggesting these cancers might be more susceptible to radiation-induced DNA damage. Since our results are constrained by the small sample size, further studies are needed to understand the relationship between PDAC with DNA repair mutations. Research Sponsor: None.

704 Poster Session

Tumor immune microenvironment of KRAS G12C mutated pancreatic cancer as compared to other mutations and non-cancer pancreata. First Author: Vaibhav Sahai, University of Michigan, Ann Arbor, MI Background: KRAS G12C mutation occurs in approximately 1% of pancreatic ductal adenocarcinoma (PDA). KRAS G12C inhibitors have a reported response rate of 21-33% in patients with previously treated advanced PDA. KRAS is a known modulator of the tumor immune microenvironment (TME) and a greater understanding of the TME in KRAS G12C as compared to other mutations is crucial for developing rational therapeutic combination strategies in PDA. Methods: We performed multiplex fluorescent immunohistochemistry (mfIHC) on tissue obtained from patients with histologically confirmed PDA (KRAS G12C n=8; other mutations n=108) and normal pancreas (n=38). Serial staining was performed using antibodies against CD3, CD8, CD163, FoxP3 and PanCK for simple and complex phenotyping as well as spatial analyses in the TME. After tyramide based signal amplification, the slides were imaged at 20x magnification using the Mantra Quantitative Pathology workstation. Images were analyzed using inForm Cell Analysis software (Akoya Biosciences). All statistical analyses were performed using JMP Pro 13.2.0. Differences in phenotype, distances, and engagement were evaluated by 2-tailed Student's t test or ANOVA. Results: Patients with KRAS G12C mutation had a median age of 70 (45-73) years of which majority (n=5, 62.5%) were men with advanced stage at diagnosis (n=6; 75%). The median overall survival is not yet reached (n=5, alive) after a median follow-up time of 14.4 months through reverse censoring methodology. When examining cellular infiltration, CD8+ cytotoxic T lymphocyte cells were significantly more abundant in the G12C TME compared to the cancer and non-cancer controls (p ,0.01). Additionally, the relative frequency of CD4+ and Tregs (CD3+/CD8-/FoxP3+) were also significantly higher in G12C (p,0.01). The percentage of CD163+ antigen presenting cells (APCs) out of all cells was significantly higher in G12C (p,0.01) while the percentage of non-functional APCs (PDL1+/CD163+) of all APCs was significantly higher in G12C than cancer and non-cancer controls (p=0.03). In comparison, the PDL1+ epithelial cells were much lower in G12C TME (p,0.01). The cellular engagement and interaction data from the spatial analysis in the TME will be presented at the meeting.

We identified increased infiltration of cytotoxic T lymphocytes and APCs in PDA patients with KRAS G12C mutations relative to other mutations and noncancerous pancreata. Furthermore, while all PDAs had elevated PD-L1 expression on APCs, KRAS G12C tumors had minimal expression on epithelial cells suggesting a mutation specific impact and a potential role of immune checkpoint inhibitors in combination with G12C inhibitors. Research Sponsor: University of Michigan Rogel Cancer Center (TF); University of Michigan Rogel Scholar (VS).

Epidemiological characteristics of patients with pancreatic cancer with and without diabetes mellitus: A retrospective cohort study. First Author: Sarah Elizabeth Eichinger, Cook County Health, Chicago, IL Background: Pancreatic cancer accounts for approximately 3% of new cancers diagnosed in the US and more than 8% of all cancer deaths. Despite the increasing incidence, there are few indicated screenings, mostly in patients with genetic mutations. Pancreatic cancer is associated with several risk factors including tobacco use, family history, heavy alcohol use, and diabetes mellitus (DM). In the US, more than 11% of adults have a diagnosis of diabetes and incidence is projected to rise over the coming years. Given the risk of DM associated with pancreatic cancer, establishing preventative measures, early intervention, and appropriate follow up for diabetic control could be an important step in decreasing the risk of pancreatic cancer. This study examines the demographic characteristics of patients with a diagnosis of pancreatic cancer with and without DM. Methods: We used the 2016-2019 Nationwide Inpatient Sample database, the largest all-payer inpatient care database in the US, to stratify all patients admitted with a diagnosis of pancreatic cancer, with and without DM, to further characterize their epidemiological characteristics.

Results: Characteristics of patients with and without DM and pancreatic cancer are shown in the table. There were 150,275 patients diagnosed with pancreatic cancer, of which 44,170 (29%) had a concomitant diagnosis of DM. Of patients with both pancreatic cancer and DM, 53% were women (51% in patients without DM), 64% were white (70% in patients without diabetes), and 63% had Medicare for insurance (60% in patients without DM). Conclusions: Of patients with pancreatic cancer 29% had a concomitant diagnosis of DM(p=0.00). Epidemiological characteristics of patients with pancreatic cancers with and without DM such as age, sex, and insurance status were similar between both groups. However, there was a decreased percentage of Caucasian patients with pancreatic cancer and DM compared to those without DM. Given the association of diabetes with pancreatic cancer, and rising incidence of patients with diabetes in the US, emphasis on diabetes prevention and control may be an important factor in reducing the incidence pancreatic cancer. This study also suggests the need for further research to determine if there is utility in screening for pancreatic cancer in patients with diabetes to decrease the burden of pancreatic cancer in the US population. Research Sponsor: None.

708 Poster Session

Impact of site of metastases in pancreatic ductal adenocarcinoma. First Author: Adeel Arshad, The Ohio State University Comprehensive Cancer Center, Columbus, OH Background: Metastatic pancreatic ductal adenocarcinoma (mPDAC) has a 5-year survival rate of 3%. We examined the clinical significance of the metastatic site on outcomes in mPDAC using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: We analyzed the data on mPDAC from SEER database from 2010-2020 and categorized into three groups: mPDAC with, liver-only (LO) metastasis (mets), multi-organ mets including the liver (IL), and multi-organ mets excluding the liver (EL). Patient demographics and disease characteristics were summarized using the mean for continuous variables and proportions for categorical variables. Overall survival (OS) was calculated from time of diagnosis to death or censored at a loss to follow-up. The survival curve was plotted using the Kaplan-Meier method and log-rank p-value was reported. The Cox regression model was used to study the association of site of distant metastasis on overall survival, controlling for potential confounders (age, race, treatment, etc.) Results: We identified 22642 patients with mPDAC; 15844, 4250, and 2548 with LO, IL, EL mets respectively. The mean age at diagnosis was 66 years with the majority being white (78.4%), non-Hispanic (87.1%), and from metropolitan counties (88.5%). The median OS was 4 months, 3 months, and 6 months (log-rank p,0.001) for LO, IL, and EL groups respectively, with 2-year survival being 4.84%, 2.56% and 7.89% respectively (log-rank p,0.001). Multivariate analysis showed a higher risk of mortality in LO (31.5%, hazards ratio (HR)=1.315, p,0.001) and IL groups (69.2% HR=1.692, p,0.001) than EL group (Table ). Conclusions: The site of distant metastasis is an independent prognostic factor for survival in patients with mPDAC, with liver-only mets or multi-organ mets including liver having worse OS than extrahepatic mets. Research Sponsor: None. Patient outcomes, such as recurrence-free survival, progression-free survival, and overall survival will also be collected. Patients will be followed up for up to 3 years after diagnosis. No a priori sample-size calculations were performed. The demographic and underlying disease characteristics will be evaluated using descriptive statistics. Timeto-event outcomes (disease-free survival, progression-free survival, and overall survival) will be estimated using the Kaplan-Meier method. From August 2023 to September 2023, 34 pts were included. The target accrual is expected to be completed by February 2024.

The results are expected to be presented in August 2024. Research Sponsor: Astellas.

TPS711 Trials in Progress Poster Session

DIsCOvER: A multicenter, randomized, double-blind, placebo-controlled, phase III clinical trial to investigate the efficacy and safety of dronabinol in the improvement of chemotherapy-induced and tumor-related symptoms in patients with locally advanced or metastatic pancreas cancer during firstline chemotherapy. First Author: Felix Keil, Hanusch-Krankenhaus Verein für Leukämieforschung, Wein, Germany Background: Patients (pts) with pancreatic cancer suffer from multiple symptoms related to the tumor itself or induced by chemotherapy (ctx). The available supportive therapy is still not able to relief all symptoms caused by the cancer itself or by the antineoplastic therapy. Additionally, anorexia and weight loss often result in increased morbidity and mortality in this population as well as in psycho-social burden and suffering. These are unmet needs in pancreatic cancer pts. Dronabinol has shown beneficial effects observed in cancer pts. However, evidence from randomized, placebo controlled trials in the use of cannabinoids for the treatment of cancer related anorexia-cachexia syndrome are lacking. Aim of this phase III trial is to investigate the efficacy and safety of dronabinol (orally administered tetrahydrocannabinol (THC)) as adjuvant, individually titrated therapy to first-line standard chemotherapy in pts with metastatic pancreas cancer for improvement of ctx-and tumor-related symptoms. Methods: Locally advanced or metastatic pancreas cancer pts from Austria and Germany with age of $18 yrs tolerating FOLFIRINOX or gemcitabine/nab-paclitaxel based ctx are eligible for enrolment. Exclusion criteria are use of dronabinol, cannabis-based medicine with THC or marihuana or relevant psychiatric disorders. The study duration for each patient will be a maximum of 18 wks treatment. Eligible pts are randomized 1:1 for treatment with dronabinol oral solution (2.5%) or placebo oral solution stratified by underlying ctx. The primary endpoint variable is the standardized area under the curve of the EORTC QLQ-C30 symptom summary score over the on-treatment period. Secondary endpoints include: other quality of life parameters, changes in Glasgow Prognostic Score, mean time to critical weightloss (5%), ctx dose intensity over the treatment of 18 wks, adverse events/reactions, PFS and OS. Changes from baseline for bioelectrical impedance analysis parameters (e.g. fatfree mass, total body water, fat mass and phase angle) and handgrip strength will be evaluated. Estimating a difference of 20% in the primary endpoint between the treatment groups with a power of 80% and an expected standard deviation of 30 a total sample size of 74 assuming a balanced design is required. A total sample size of 104 pts is needed with expected drop-out rate of 30 pts. Enrolment started in 2019 and continues until 2024. The DIsCOvER trial is the first randomized, placebo-controlled phase III trial that investigates the impact of individually dosed dronabinol in cancer pts (Registration: NCT03984214). Clinical trial information: NCT03984214. Research Sponsor: AGMT.

TPS712 Trials in Progress Poster Session

A phase 1b/2 trial of pepinemab and avelumab as second line therapy for patients with metastatic pancreatic adenocarcinoma. First Author: Bailey Hilty, University of Rochester Cancer Center & Wilmot Cancer Institute, Rochester, NY Background: Pancreatic adenocarcinoma (PDAC) is a leading cause of cancer-related mortality with poor prognosis despite maximal therapy and is unresponsive to immune checkpoint blockade (ICB). This failure of response is hypothesized to be driven in part by the characteristic immunosuppressive tumor microenvironment. In PDAC, Semaphorin 4D (SEMA4D) expression is prognostic in patients who have undergone surgical resection and correlates with tumor infiltration of activated CD8+ T-cells. Additionally, preclinical models suggest that antibody-mediated SEMA4D blockade promotes tumoral infiltration and activation of CD8+ T-cells and sensitizes PDAC to ICB, with improved overall survival with standard of care chemotherapy and ICB in combination with pepinemab (humanized anti-SEMA4D). Thus, we hypothesized that pepinemab may improve clinical outcomes in PDAC by sensitizing tumors to ICB. Methods: We designed a phase Ib/II single-arm clinical trial to evaluate the safety, tolerability, and efficacy of humanized anti-SEMA4D (pepinemab) with anti-PD-L1 (avelumab) in patients with chemotherapy-refractory PDAC. Patients must have failed first-line 5-fluorouracil or gemcitabine-based combination chemotherapy. The study follows a dose de-escalation schema starting at a dose combination of 20mg/kg pepinemab and 800mg avelumab every two weeks. Patient accrual for phase 1b utilizes the Bayesian Optimal Interval Design (BOIN) targeting a dose-limiting toxicity rate of 30% or less. After 16 subjects receive a given combination dose, a Simon's two stage assessment of futility will be undertaken with expansion to phase 2 if 2 or more subjects demonstrate response. The trial is designed to evaluate a total cohort of 40 subjects and powered to detect a response rate of 23% or greater, with alpha set at 0.1% and 80% power. A phase 1 trial of combined MEK, STAT3 and PD-1 inhibition in metastatic pancreatic ductal adenocarcinoma (PDAC). First Author: Peter Joel Hosein, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL Background: PDAC is characterized by its innate and acquired resistance to both MAPK pathway inhibition and immune checkpoint (e.g. PD-1/PD-L1) inhibition (ICI) via multiple mechanisms. In preclinical models of PDAC, combined MEK and STAT3 inhibition (MEKi+STAT3i) uncovers stromal plasticity by attenuating cancer-associated fibroblasts (CAF) with IL-6/CXCL1-secretory phenotypes while enriching for Ly6a/CD34-expressing CAF phenotypes with mesenchymal stem cell-like features. This remodeling of CAF heterogeneity is associated with a striking attenuation in and reprogramming of tumorassociated macrophages (TAMs) as well as enhanced trafficking of CD8 T cells, which exhibit a distinct effector and anti-apoptotic transcriptional program. The addition of MEKi+STAT3i to PD-1 blockade overcomes ICI resistance by significantly enhancing the recruitment, degranulating capacity, and functional cytotoxicity of CD8 + T-cells, thereby augmenting antitumor responses and dramatically improving survival in these models. Furthermore, a patient with refractory PDAC treated off-label with this combination achieved a meaningful response. Based on this strong rationale, a phase 1 trial was initiated to test the combination of MEKi+STAT3 and PD1 inhibition in patients with metastatic PDAC. Methods: NCT05440942 is an open-label, prospective, singleinstitution phase 1 trial testing the safety, preliminary efficacy, and biomarkers of response to the combination of trametinib (MEKi), ruxolitinib (JAK2/STAT3 inhibitor) and retifanlimab (PD-1 inhibitor) in patients with metastatic PDAC. Patients with metastatic PDAC who have had disease progression on at least one line of prior therapy, with good organ function, preserved performance status, and without major intercurrent illness are eligible. Patients must have an accessible lesion for biopsy and must be willing to undergo this research biopsy at baseline and on treatment. Part 1 of the study is a dose-escalation phase with 3 dose levels and a target dose of trametinib 2mg orally daily, ruxolitinib 15mg orally twice daily, and retifanlimab 500mg intravenously every 28 days. The dose escalation is being done using the novel Bayesian keyboard design and 9-15 patients will be treated to get to the potential maximum tolerated dose (MTD). Dose level 1 has been completed without any dose-limiting toxicities seen. Part 2 is an expansion phase which will accrue an additional 20 patients. All patients in part 1 and 2 will have core-needle biopsies pre-treatment and after 4 weeks. Serial blood samples will be collected at baseline and on treatment. Biopsies are being analyzed by multiparameter immune profiling using mass cytometry and bulk RNA sequencing; blood is being analyzed for circulating tumor DNA and immune profiling. These results will be correlated with clinical response to therapy to determine biomarkers of response and resistance. Clinical trial information: NCT05440942. Research Sponsor: None.

TPS714 Trials in Progress Poster Session

AIRPanc: A phase 2, open-label, multicenter, randomized study evaluating neoadjuvant therapy targeting the adenosine immunosuppressive pathway in combination with immune checkpoint blockade and radiation therapy in patients with advanced pancreatic ductal adenocarcinoma who are candidates for surgical resection. First Author: Gulam Abbas Manji, Columbia University Herbert Irving Comprehensive Cancer Center, New York, NY Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease for which immune checkpoint blockade (ICB) has not provided benefit, hypothesized to be due to the presence of an immunosuppressive tumor microenvironment (TME). Neoadjuvant multi-agent chemotherapy and stereotactic body radiation therapy (SBRT) may increase immunosuppression by elevating intratumoral levels of adenosine, an immunosuppressive metabolite. Adenosine, produced from adenosine triphosphate by enzymes CD39 and CD73, binds the adenosine 2a and 2b receptors (A2aR and A2bR) expressed on immune cells and inhibits critical components of the antitumor immune response. Human PDAC expresses high levels of CD73, which is strongly associated with worse progression-free survival. Preclinical investigation has demonstrated CD73 and A2aR inhibition enhances antitumor immune responses, including increasing activity of ICB. The goal of this study is to test inhibition of the adenosine immunosuppressive pathway in combination with ICB and SBRT in patients with advanced PDAC who are candidates for surgical resection after receiving neoadjuvant chemotherapy. Methods: This investigator-initiated, open-label, multicenter, phase 2 clinical trial will randomize patients with borderline resectable or locally advanced PDAC who have completed 8 cycles of neoadjuvant mFOLFIRINOX and are eligible for SBRT to one of three treatment arms: zimberelimab (anti-PD-1) alone (Arm A), zimberelimab plus quemliclustat (anti-CD73) (Arm B), or zimberelimab plus quemliclustat and etrumadenant (A2aR/A2bR inhibitor)(Arm C) for a period of 7 weeks prior to undergoing surgical resection. 40 Gy SBRT in 5 fractions, totaling a biologically effective dose (BED) of 72 Gy, will be delivered concurrently to all randomized patients starting week 2 of study treatment. Part I will comprise a six-patient safety run-in with a dose-deescalation design in which patients will be treated according to Arm C with a plan for subsequent enrollment of 14 additional patients per arm (N=42) in Part II. The primary endpoint is CD8+ T-cell infiltration at the time of surgery compared between combination arms and Arm A. Group sample sizes of 14 achieve at least 80% power to detect an effect size of 1.23 with a significance level (alpha) of 0.05 using a two-sided two-sample t-test and adjustment for 2 comparisons. Secondary objectives include estimation of median OS, 18-month survival rate, R0 resection rate, safety profile and CA 19-9 biomarker response. Exploratory studies interrogating the tumor immune microenvironment will be performed on surgical resection specimens. The trial was opened for enrollment on May 19 th , 2023. Clinical trial information: NCT06048484. Research Sponsor: None.

TPS715 Trials in Progress Poster Session

A phase Ib/II study of atezolizumab plus tivozanib in pancreatic, gallbladder, and bile duct malignancies. First Author: Brian Hemendra Ramnaraign, University of Florida/UF Health Cancer Center, Gainesville, FL Background: Checkpoint inhibitor therapy represents a significant advance in cancer care however it is not an effective intervention in the treatment of several immunologically cold tumors including pancreatic, gallbladder, and bile duct malignancies where checkpoint inhibitors have produced objective response rates ranging from 0-6%. VEGF is thought to play a key role in modulating the anti-tumor immune response as it is secreted by tumors and leads to endothelial cell proliferation, vascular permeability, and vasodilation. This in turn leads to the development of an abnormal vasculature with excessive permeability and poor blood flow, thus limiting immune surveillance. In addition, VEGF inhibits dendritic cell differentiation, limiting the presentation of tumor antigens to CD4 and CD8 T cells. Through the inhibition of VEGF, it may be possible to potentiate the effect of immune checkpoint blockade. Combined use of a VEGF receptor tyrosine kinase inhibitor (TKI) and checkpoint inhibitor is already standard of care in advanced kidney and cervical cancers. Methods: This is a single institution, single arm, open-label phase Ib/II study with the co-primary endpoints of safety and efficacy of the combination of the VEGF receptor TKI tivozanib and checkpoint inhibitor atezolizumab. Eligible patients will include those with pancreatic, gallbladder, and bile duct cancers, as well as well-differentiated grade 2 and 3 neuroendocrine tumors, ovarian and vulvar cancer, soft tissue sarcoma, castrate resistant prostate cancer, and HER2 positive hormone receptor negative breast cancer, that is metastatic and progressed on at least one line of therapy. Key exclusion criteria will include patients with known mismatch repair deficiency, microsatellite instability, or high tumor mutational burden. The phase Ib portion will assess the safety profile of the combination of tivozanib and atezolizumab with a potential dose deescalation of tivozanib using a 3+3 study design. Three patients will be treated at the dose of tivozanib 1.34 mg per day (dose level 0) for 21 days of each 28-day cycle and atezolizumab 1680 mg on day 1 of every 28-day cycle. If one dose limiting toxicity (DLT) is found then 3 more patients will be enrolled at dose level 0. If .1 DLT occurs in the first 3 patients or .1 DLT in the first 6, another 3+3 study will begin at dose level -1 (0.89 mg of tivozantib). If 1 DLT occurs in these 3 patients at dose level -1 then another 3 will be enrolled at this dose. The study will be stopped for toxicity if there is .1 DLT in the first 3 patients at dose level -1 or if there are .1 DLT in the 6 patients at dose level -1. The phase II portion will enroll up to 26 patients using the dose of tivozanib found to be safe in the Ib portion. Disease response assessment every 12 weeks with CT Chest, Abdomen, and Pelvis via RECIST 1.1. Treatment will continue until progression or intolerance. Clinical trial information: NCT05000294. Research Sponsor: AVEO Oncology; Genentech; University of Florida Health Cancer Center.

TPS716 Trials in Progress Poster Session

COVALENT-102: A phase 1/1b dose finding study of BMF-219, an oral covalent menin inhibitor, in adults with locally advanced, unresectable, or metastatic non-small cell lung cancer (NSCLC), pancreatic cancer (PDAC) and colorectal cancer (CRC) with activating KRAS mutations. First Author: Christos Fountzilas, Roswell Park Comprehensive Cancer Center, Buffalo, NY Background: BMF-219 is a selective covalent inhibitor of menin, a transcriptional regulator of oncogenic signaling pathways in multiple cancers, that inhibits the menin/ MYC interaction and downregulates the expression of MYC and MYC target genes, including KRAS. In addition, inhibition of the menin complex by BMF-219 alters function of the AP-1 transcription factor, JunD, a crucial factor for KRAS-driven tumorigenesis. Further, inhibition of the menin-MLL complex suppresses expression of Rasgrf1, a guanine nucleotide exchange factor essential for generation of the active RAS-GTP conformation of KRAS, activation of downstream pathways, and tumorigenesis. Preclinically, BMF-219 shows potent abrogation of menin-dependent oncogenic signaling and exerts pan-mutant KRAS anticancer activity independent of the specific KRASactivating mutation.

TPS719 Trials in Progress Poster Session

A phase II open-label study of enfortumab vedotin in patients with previously treated locally advanced, recurrent, or metastatic pancreatic adenocarcinoma (EPIC). First Author: Anup Kasi, University of Kansas Cancer Center, Kansas City, KS Background: Nectin-4 is a type I transmembrane protein member of the nectin family involved in the formation and maintenance of adherens junctions. In contrast to its limited expression in normal tissues, aberrant overexpression of nectin-4 has been identified in various solid tumors, including in pancreatic adenocarcinoma. About 71% of human PDAC specimens stain positive and 13% stain strongly positive for nectin-4. Mechanistically, nectin-4 has been associated with various pro-oncogenic cellular processes, including the promotion of tumor cell proliferation and metastasis via WNT-bcatenin pathway activation. It interacts with ERBB2/HER2 and activates Rac1 (small G protein) to ultimately upregulate PI3K-AKT pathway signaling, leading to cell survival and proliferation. Enfortumab vedotin (EV) is an antibody-drug conjugate that delivers the microtubuledisrupting agent monomethyl auristatin E (MMAE) to cells expressing Nectin-4. EV is FDA approved as a single agent for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and platinum-containing chemotherapy based on the EV-301 Trial which demonstrated overall survival benefit. Taken together, the above data and the efficacy of EV seen in bladder cancer warrants the evaluation of EV in advanced pancreatic adenocarcinoma. Methods: Design: Open-label, phase II single-arm trial of EV (n=28) in previously treated locally advanced, recurrent, or metastatic pancreatic adenocarcinoma. Treatment schedule: EV 1.25 mg/kg administered IV on D1, D8, D15 every 28 days until disease progression or unacceptable toxicity. Imaging assessment will be done every 8 weeks. A biopsy prior to therapy and a biopsy on treatment (between days 15-21 of cycle 1) is required. Eligibility: Patients with previously treated, locally advanced, recurrent, or metastatic pancreatic adenocarcinoma. Inclusion criteria also include ECOG PS 0-1 and at least 1 line of prior therapy. Objectives: The primary objective is to determine anti-tumor activity by overall response rate using RECIST 1.1. Secondary objectives include safety, duration of response, disease control rate, progression-free survival and overall survival. Exploratory objectives include Nectin-4 expression (H-score) in tumor tissue and the relationship between the mutational profile of the tumor and response. Statistical Plan: A Simon's two-stage Minimax design will be used. In the first stage, 18 pts will be accrued. If there is less than 1 response in these 18 pts, the study will be stopped for futility. Otherwise, 10 additional pts will be accrued for a total of 28 pts. The null hypothesis will be rejected if 3 or more responses are observed in 28 pts. Enrollment is currently ongoing. Clinical trial information: NCT05915351. Research Sponsor: Astellas Pharma Global Development, Inc./Seagen Inc.

TPS720 Trials in Progress Poster Session

AMPLIFY-7P: Phase 1 and randomized phase 2 study of amphiphile immunotherapy ELI-002 7P as adjuvant treatment for subjects with G12D, G12R, G12V, G12C, G12A, G12S and G13D Kirsten rat sarcoma (KRAS)mutated pancreatic ductal adenocarcinoma. First Author: Zev A. Wainberg, UCLA School of Medicine, Los Angeles, CA Background: KRAS mutations occur in 25% of human tumors, frequently in pancreatic where over 85% relapse after locoregional treatment. ELI-002 2P is a lymph node targeted immunotherapy comprised of Amphiphile (Amph)-modified G12D, G12R, G12V, G12C, G12A, G12S and G13D mutant KRAS peptides together with an Amph-modified CpG oligonucleotide adjuvant. In the first in human AMPLIFY-201 study, a two peptide G12D/G12R formulation increased KRAS-specific T cells in 87% of patients, and T cell responses 13-fold or higher over baseline correlated with outcomes including reduction in risk of relapse or death. The AMPLIFY-7P study hypothesizes that adjuvant administration of ELI-002 7P will be safe and will delay relapse compared to observation in patients with KRAS mutated pancreatic cancers who have completed curative intent locoregional treatment.

Methods: This open-label, phase 1 and randomized phase 2 study is evaluating ELI-002 7P in patients with KRAS mutated pancreatic adenocarcinoma following standard of care chemotherapy and surgery. In phase 2, patients are randomized 2:1 to ELI-002 7P versus observation with crossover of the observation arm permitted at the time of confirmed radiographic relapse via iRECIST. Eligible patients must be within 6 months of completion of locoregional treatment for up-front resectable pathologically confirmed pancreatic cancer (Stage I-III) with radiographic NED (no evidence of disease). Phase 2 patients are included regardless of biomarker evidence of recurrent disease, however, those who have not recovered absolute lymphocytes to the normal range following cytotoxic therapy are excluded. The primary phase 2 objective is to compare the efficacy of ELI-002 7P versus observation, with primary endpoint disease-free survival per investigator. Secondary objectives compare biomarker response (reduction or clearance of ctDNA or if ctDNA was not detectable, serum tumor antigen CA19-9) in the subset with positive baseline values, OS, safety, and iRECIST response rate in the crossover subset. Exploratory endpoints include immunogenicity, the association of immunogenicity with high resolution HLA typing, and evaluation of tumorinfiltrating T cells and the tumor microenvironment in the event biopsy tissue is available. An Independent Data Monitoring Committee reviewed phase 1 data and recommended opening phase 2. Subsequent patients will receive up to 10 doses of Amph-peptides 7P 700 mcg each (4.9 mg total), together with Amph-CpG-7909 (10.0 mg) administered over a fivemonth treatment period. In Phase 2, approximately 135 patients will be enrolled in the United States. An interim analysis is planned using group sequential design for control of overall alpha 0.10. Clinical trial information: NCT05726864. Research Sponsor: None.

Multicenter study of circulating tumor DNA in patients with pancreatic cancer using a personalized panel: ARTEMIS-PC prospective observational trial. First Author: Edward D. Esplin, Invitae, San Francisco, CA Background: With very low survival rates, pancreatic cancer (PC) remains a disease in need of diagnostic and therapeutic innovation and novel biomarkers to guide and optimize treatment decisions are urgently needed. Analysis of circulating tumor DNA (ctDNA) has been shown to be a highly accurate method for determining treatment efficacy and detecting molecular residual disease (MRD) in patients (pts) with various cancer types as compared to tumor markers and imaging modalities. However, it has been reported that the ctDNA detection rate in PC using existing tumor-agnostic ctDNA assays was lower than those in other cancer types because of the high stromal and low cellular features of PC, which prevents the shedding of ctDNA into blood circulation. Even in advanced cancers, the sensitivity of ctDNA utilizing tumor-agnostic mutation panels is much lower as compared to that in tumor tissue specimens. The Invitae Personalized Cancer MonitoringTM test is a novel and highly sensitive, tumor-informed MRD detection assay. MRD assessment as well as recurrence and treatment response monitoring using this novel assay could lead to the development of improved treatment algorithms for pts with PC. The ARTEMIS-PC study (UMIN000043561) aims to evaluate the clinical utility of the Invitae Personalized Cancer Monitoring test in pts with resectable and unresectable PC. Methods: This is a multi-site, prospective, observational trial in Japan of 150 pts with resectable (50) and unresectable (100) PC. The main eligibility criteria are histopathologically diagnosed as adenocarcinoma, no prior treatment for PC, scheduled to undergo surgery for resectable PC or receive systemic therapy for unresectable PC. In resectable PC cohort, blood samples will be collected before surgery and at 1, 3, 6, 9, 12, 18, and 24 months after surgery, and imaging study will be performed before surgery, and at 3, 6, 9, 12, 18, and 24 months after surgery. In the unresectable PC cohort, blood samples will be collected before treatment and at 4, 8, 12, 16, 24, 32, 40, and

734 Poster Session

Examining the prevalence of anxiety and depression in surgical oncology patients: Results of a prospective cohort study. First Author: Judy Li, Department of Surgery, Division of Surgical Oncology at Icahn School of Medicine at Mount Sinai, New York, NY Background: Prospective data assessing prevalence of anxiety and depression in a diverse surgical oncology population are currently lacking. Psychological distress may affect patient outcomes in the postoperative setting. The General Anxiety Disorder (GAD) and Patient Health Questionnaire (PHQ9) surveys are validated instruments to assess severity of anxiety and depression, respectively. We aimed to determine the prevalence of anxiety and depression using validated screening tools, and assess associations between anxiety and depression with clinical outcomes in patients presenting to our surgical oncology clinic. Methods: A prospective, surgeon-blinded study was conducted to assess associations of anxiety and depression with postoperative outcomes in patients with histologically proven malignancy who underwent surgical intervention. Preoperatively, the GAD and PHQ9 surveys were administered to evaluate for anxiety and depression, respectively. Frailty level was also assessed using the validated Risk Analysis Index (RAI-C) survey. Postoperative outcomes included rates of ICU admission, 30-and 90-day readmissions, postoperative complications classified by Clavien-Dindo score, and disposition to home versus rehabilitation facilities. Outcomes were compared between different groups as defined by the severity of anxiety and depression. Results: 191 patients met inclusion criteria. The cohort was stratified into three groups by severity of anxiety and depression. Overall, 59 (31%) patients reported at least moderate anxiety as defined by a GAD score $5, with 30 (15.7%) patients reporting severe anxiety (GAD score $ 10). Similarly, 62 (32%) patients reported at least mild depression as defined by a PHQ9 score $5, with 21 (11%) patients experiencing moderate to severe depression (PHQ9 $ 10). No difference was detected in length of stay, ICU admission, 30-and 90-day readmission, and postoperative complications.

Preoperative frailty, as defined by RAI-C score .21, was also not associated with anxiety or depression. Marital status of single or widowed was found to be significantly associated with mild depression (p=0.027) and moderate to severe depression (p=0.028), respectively. Conclusions: While anxiety and depression were not found to be significantly associated with postoperative outcomes, they are prevalent in surgical oncology patients, affecting approximately one-third of our patient population. The GAD and PHQ9 surveys are validated instruments that can be administered easily to identify surgical oncology patients with psychological distress. Comprehensive evaluation of psychological well-being, in conjunction with a thorough social evaluation, can identify those patients who may benefit from referral to supportive resources. Research Sponsor: None.

735 Poster Session

Liquid biopsy-based comprehensive genomic profiling to reveal mutational landscape in real-world patients with gastrointestinal cancer. First Author: Haoran Tang, Huidu Shanghai Medical Sciences, Ltd., Shanghai, China

Background: Molecular characteristics hold substantial clinical significance in cancer.

Previous research has elucidated the molecular classification of gastrointestinal (GI) cancers, leveraging biomarkers like gene alterations, MSI, EBV status, and chromosomal instability. However, most of these studies relied on tissue biopsies. Limited investigations have been documented regarding the characterization of molecular profiles through liquid biopsy. Here we present a comprehensive genomic profiling study conducted on advanced GI cancer patients using blood samples. Methods: This prospective study is a part of a global initiative focused on molecular biomarker screening across various solid tumors. Here we report the early result of 106 unresectable GI cancer patients, encompassing those with advanced disease or experiencing relapse after prior treatments. The cohort comprises 66 colorectal cancer (CRC) patients, 34 gastric cancer (GC) patients, and 6 esophageal cancer (EC) patients.

Each patient contributed a 10-mL blood sample for comprehensive circulating tumor DNA (ctDNA) analysis. The study employed PredicineCARE, a 152-gene, NGS-based liquid biopsy assay, to profile somatic gene variations within this patient population. Results: The study revealed a total of 1,597 somatic mutations, with 1,077 occurring in CRC, 448 in GC, and 72 in EC. Additionally, 722 gene copy number variants were identified, with 288 in CRC, 351 in GC, and 83 in EC patients. In CRC, the most frequently altered genes (prevalence . 20%) included TP53 (58%), APC (45%), KRAS (33%), and BRCA2 (22%). Conversely, in GC, the most altered genes were TP53 (59%), TERT (35%), FAT1 (29%), ARID1A (26%), and FGFR4 (24%). Among the 6 EC patients, 3 carried TP53 variations, with variations in APC (N=2), ERCC5 (N=2), FAT1 (N=2), and EGFR (N=1) also observed. The mutation burden in CRC (median 3.73 mut/Mb) and GC (median 3.57 mut/Mb) displayed no significant differences. However, the mutation burden in CRC was significantly higher than that in EC (2.24 mut/Mb) (p=0.04). A similar pattern was observed between GC and EC but did not reach statistical significance (p=0.10) due to limitations in cohort size. Furthermore, the assay identified patients carrying both germline and somatic mutations related to homologous recombination deficiency (HRD). In CRC patients, 5 had MLH1 germline mutations, 6 had MSH2 mutations (5 were germline), 4 had MSH6 germline mutations, 2 had PMS2 somatic mutations, and 1 had an EPCAM germline mutation. While in GC patients, 2 had MLH1 germline mutations, 1 had an MSH6 mutation, and 1 had a PMS2 somatic mutation. Conclusions: This study elucidated the comprehensive mutational landscape of advanced gastrointestinal cancer through liquid biopsy, thereby contributing novel biomarkers for clinical diagnosis and facilitating targeted therapy mechanism investigations. Research Sponsor: None.

736 Poster Session

Initial findings from the DREAM-GI national database: Assessing the efficacy and safety of neoadjuvant immunotherapy (NIT) in patients with deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) gastrointestinal (GI) cancer. First Author: Sakti Chakrabarti, Department of Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH Background: Patients with dMMR/MSI-H gastrointestinal (GI) cancer occasionally receive neoadjuvant immunotherapy (NIT) due to various clinical considerations. To systematically evaluate the outcome of these patients, we initiated the DREAM-GI national database, intending to harness real-world data to provide crucial insights into the outcomes, safety profile, and response patterns of dMMR/MSI-H GI cancer patients undergoing NIT. Herein, we present the initial findings. Methods: We developed a centralized database to collect deidentified clinical data from patients with dMMR/MSI-H GI cancers receiving NIT. We collected data retrospectively and prospectively through September 15, 2023. Results: The current report includes 50 patients with a median age of 67 years (range 32 to 90); 21 (42%) were female, 9 (18%) were Black, and the remaining were White. The cohort included the following tumor types-31 (62%) colorectal, 7 (14%) gastroesophageal, and 12 (24 %) pancreaticobiliary. Most patients had localized disease (34, 68%), while the rest had oligometastatic disease. NIT consisted of pembrolizumab monotherapy in 40 (80%) patients, ipilimumab plus nivolumab in 8 (16%), and nivolumab plus chemotherapy in 2 (4%) patients. Most patients, 33 (66%), were treatment-naive. The median duration of NIT was 6 months (range: 1.5 to 55), with a time to best response of 3 months (range: 1.5 to 12). Among 47 evaluable patients, the best responses were as follows: an overall response rate of 75% (35/47), consisting of radiologic complete response (CR) in 20 (43%), pathologic CR in 4 (9%), and partial response in 11 (24%). The median progression-free survival and overall survival were not reached after a median followup of 14 months (range: 2-80), calculated from the date of the first immunotherapy dose to the last follow-up or death. Among 24 patients achieving CR, all remained progression-free after a median follow-up of 25.5 months (range: 3-80). Stable and progressive diseases were observed in 7 (15%) and 5 (10%) patients, respectively. Only 5 (10%) patients underwent surgery following NIT, with 4 (80%) achieving pathologic CR. The reasons for not proceeding with surgery were comorbidities in 40 (80%) patients, disease extent in 4 (8%), and patient refusal in 1 (2%). Out of the 12 patients who expired at the data cut-off, 1 was due to immunotherapyrelated pneumonitis, 6 due to disease progression, and the remainder from underlying comorbidities. Conclusions: Our study underscores the remarkable response rates and durability of responses achieved with NIT in patients with dMMR/MSI-H GI cancers. Progression on NIT was infrequent. These real-world data support further investigation into non-operative approaches for patients with dMMR/MSI-H GI cancers. Research Sponsor: None.

Characteristics and predictors of outcomes with neoadjuvant imatinib in gastrointestinal stromal tumors: Real-world data from a large patient registry. First Author: Udhayvir Singh Grewal, University of Iowa Hospitals and Clinics, Iowa City, IA Background: The standard of care for patients with moderate or high-risk resectable gastrointestinal stromal tumors (GIST) is surgical resection followed by adjuvant therapy with imatinib. The impact of neoadjuvant imatinib on long-term outcomes is largely unknown. Methods: We interrogated the LifeRaft registry, a large international open cohort of patients with GIST. We included patients who did not have metastatic disease at diagnosis, underwent surgical resection and received neoadjuvant imatinib and had no recorded mutations of Kit exon 13 or PDGFRA exon 18 D842V. Baseline patient characteristics were described and survival probabilities were estimated and plotted using the Kaplan-Meier method. Cox regression was used to estimate the effect of demographic and clinical characteristics on recurrence-free survival (RFS) and overall survival (OS). For RFS, time was calculated from the date of surgery to disease recurrence/death, whichever came first. For OS, time was calculated from the date of surgery to death. Estimated effects of predictors were reported as hazard ratios (HR) along with 95% confidence intervals (CI). All statistical testing was two-sided and assessed for significance at the 5% level using SAS v9.4 (SAS Institute, Cary, NC). Results: Out 2,472 patients with GIST, 137 patients met the inclusion criteria and received neoadjuvant imatinib for a median of 6.8 months. Majority of the patients were aged 40 years or above (129/ 137, 94.2%) and were males (73/137, 53.3%). The majority of the patients had gastric GIST (72/ 137, 54.1%), followed by small intestine GIST (34/137, 25.6%) and other (27/137, 20.3%). Most patients had a tumor size of .10 cm (66/137, 52.4%) at the time of diagnosis followed by .5 cm -,=10 cm (42/137, 33.3%) and .2 cm -,=5 cm (18/137, 14.3%). The median RFS for the cohort was 6.1 years. On multivariable analysis, tumor size (HR 1.08, 95% CI 1.05-1.12, p,0.01) and the overall duration of treatment (neoadjuvant and adjuvant) with imatinib therapy (HR 0.98, 95% CI 0.97-0.99, p,0.01) were significantly associated with RFS. A 1-cm increase in tumor size and 1-month increase in total time on imatinib was associated with an 8% increase and 2% decrease in risk of recurrence. The median OS was 14.2 years. Female gender (HR 0.23 95% CI 0.08-0.65, p,0.01) and total length of time on imatinib (HR 0.97 95% CI 0.96-0.99, p,0.01) were found to be significantly associated with OS. Female patients were associated with a 77% decreased risk of death and a 1-month increase in the total time on imatinib was associated with a 3% decrease in the risk of death. Conclusions: We show that most patients receiving neoadjuvant imatinib have gastric GIST with tumor size .10 cm. Smaller tumor size and female gender predicted longer RFS and OS respectively. Longer total duration of imatinib therapy was associated with increased RFS and OS. Research Sponsor: None.

738 Poster Session

Real-world data of anlotinib for gastrointestinal tumors with liver metastases in China. First Author: Yujia Zhu, Sun Yat-sen University Cancer Center, Guangzhou, China Background: Patients with advanced gastrointestinal tumors, such as gastric cancer (GC), colorectal cancer (CRC), esophageal squamous cell carcinoma (ESCC), biliary tract cancer (BTC) and pancreatic cancer (PC), often develop liver metastases with poor prognosis. Recent clinical studies have implicated that anlotinib (a novel antiangiogenesis agent) could improve survival outcomes in gastrointestinal tumors with liver metastases, albeit with limited real-world evidence. This study aimed to report the efficacy and safety of anlotinib for gastrointestinal tumors with liver metastases in real-world practice. Methods: Demographic and clinical data of patients treated with anlotinib in any line of treatment for solid tumors with liver metastases (excluding primary liver cancer) was collected retrospectively through 5 large hospitals in China, between Jan, 2016 and Feb, 2023. The primary endpoints were progression-free survival (PFS) and objective overall response (ORR). Secondary endpoints included overall survival (OS), hepatic PFS (hPFS), hepatic ORR (hORR) and safety. In this abstract, we present data from patients with gastrointestinal tumors. PFS, hPFS and OS were estimated using the Kaplan-Meier method and compared using the log-rank test.

Results: A total of 475 patients were enrolled in the study and 238 patients with gastrointestinal tumors were analyzed, including 73 (30.7%) GC, 71 (29.8%) CRC, 46 (19.3%) ESCC, 24 (10.1%) PC, and 24 (10.1%) BTC. 75.2% were ,75 years old, 82.4% were male, 63.9% had a normal body mass index (BMI) (18.5-24 kg/m 2 ), 87.8% received third-line anlotinib, and 90.3% received anlotinib monotherapy. At data cut-off (Feb 28, 2023), the median PFS was 5.90 months (95% CI: 5.23-6.77), the median hPFS was 6.20 months (95% CI: 5.27-6.77), and the median OS was 9.37 months (95% CI: 8.40-NR).

There was no statistically significant difference according to the tumor types in terms of PFS (p=0.66), hPFS (p=0.8) and OS (p=0.72). We also found patients with a BMI , 18.5 kg/m 2 had significantly shorter PFS (p=0.005) and hPFS (p=0.01). Adverse events (AEs) were manageable and tolerable, 30 (12.6%) patients had treatmentemergent adverse events (TEAEs) and 3 patients (1.3%) had $3 TEAEs. The most common treatment-related adverse events (TRAEs) were leukopenia (5.9%).

Conclusions: To our knowledge, this is the first real-world report about anlotinib for gastrointestinal tumors with liver metastases in China, showed the clinical benefit of anlotinib in any line of treatment for gastrointestinal tumors with liver metastases and indicated that anlotinib could be a feasible treatment option in this specific population.

739 Poster Session

Multicenter clinical validation of GutSeer: A cost-effective, blood-based assay for early detection and localization of major gastrointestinal cancers.

740 Poster Session

A review of comprehensive genomic profiling testing in a Japanese single institution. First Author: Nozomi Funatsu, Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan Background: In Japan, comprehensive genomic profiling (CGP) testing, including OncoGuide and FoundationOne CDx (F-1), were approved in June 2019 for patients with advanced solid tumors. Here, we report the landscape of CGP testing in our hospital. Methods: This study was conducted with a retrospective design to evaluate the clinicogenomic characteristics of patients who underwent CGP testing. OncoGuide is a panel using matched tumor tissue and blood sample, containing 124 genes, developed by the National Cancer Center. F1 is a tumor-only panel, containing 324 genes, developed by Foundation Medicine Industry. Results: Of the 460 patients enrolled in this study, 376 and 84 underwent F-1 and OncoGuide, respectively. The most common primary tumor was colorectal cancer (93 pts), followed by malignant melanoma (33 pts) and pancreatic cancer (33 pts). Actionable gene alteration was detected in 304 patients (66.1%). The detected actionable genes were TP53 (55.9%), APC (27.8%), KRAS (22.6%), and BRAF (8.5%) in colorectal cancer, BRAF (10.1%), CDKN2A (30.2%), CDKN2B (9.4%), and TERT (33.3%) in malignant melanoma, and KRAS (18.8%), TP53 (54.3%), and CDKN2A (21.8%) in pancreatic cancer. The mean time from sample shipment to result receipt was 42.5 days. As a result of CGP testing, candidate anticancer drugs were found in 304 patients: however, 108 patients were not treated due to poor general condition, complications, or age, which limited access to clinical trials. In germline findings, a pathogenic germline variant of BRCA2 was detected in one patient in OncoGuide, and presumed germline pathogenic variants of MLH1, BRCA2, and PTEN were detected in 1, 13, 26 patients in F-1. Conclusions: In Japan, CGP testing found candidate anticancer drugs, however it requires a significant amount of time to receive treatment because of limiting access to ongoing clinical trials and being typically performed after standard chemotherapy. Therefore, improving access to clinical trials, including determining the timing of testing and selecting appropriate cases, was critical. Research Sponsor: None.

Alterations in muscle strength among patients with GI cancers receiving oral nutritional support as soon as malnutrition was detected: ONMUS study. First Author: Ahmet Ozveren, Acibadem Kent Hospital, Izmir, Turkey

Background: The main goal of our multicenter study, focusing on patients with gastrointestinal (GI) cancers receiving nutritional support, was to monitor the alterations in muscle strength among individuals who began oral nutritional support (ONS) as soon as malnutrition was detected. Additionally, our study had secondary objectives, which included assessing the adherence to ONS, examining the impact of ONS on anthropometric measurements, analyzing chemotherapy compliance, and evaluating the overall quality of life. Methods: The ONMUS study was conducted at 8 centers in Turkey. The study aimed to involve patients with GI cancer who had used ONS for a minimum of 1 week and had an ECOG performance score of 0-1. Patients underwent evaluations by both a dietitian and an oncologist during the baseline visit, as well as at the 2nd and 3rd month visits. Various parameters, including age, gender, performance status, disease stage, treatment adherence, food consumption records, anthropometric measurements, muscle function measured with a handgrip device, and quality of life scales, were assessed. Results: The study comprised 426 patients. The median age was 62 years, with a range spanning from 19 to 90 years. Colorectal cancer was the primary diagnosis in 51% of the patients, while hepatobiliary, gastric, esophageal, and small bowel cancers accounted for 20.9%, 20.7%, 6.5%, and 1% of cases, respectively. A significant majority, 78.2% (n=319), of the patients were diagnosed at stage 4, and nearly all, 99.3% (n=411), were undergoing chemotherapy. Patients who adhered to ONS at or above 75% of the recommended usage were categorized as compliant. Among this group, there was a significant increase in body mass index (P=0.005). Handgrip measurements for assessing muscle strength demonstrated a statistically significant increase, with handgrip weight rising from 24.9 6 8.9 kg at the first visit to 26.1 6 8.9 kg at the third visit (P=0.009). ONS-compliant patients also showed statistically significant improvements in weight, total body water, basal metabolic rate, and calf circumference measurements. The proportion of ONS-compliant patients decreased from 80.5% (n=343) at the first visit to 62.4% (n=93) at the third visit. Additionally, a statistically significant improvement was observed in food consumption records (P=0.004). In assessments using the EORTC QLQ-C30, there were significant improvements noted in general health status, fatigue, pain, and insomnia scales, as well as in physical, emotional, and social functioning. Furthermore, a significant difference was identified between visits 1 and 2 in PG-SGA scoring (P,0.001). Conclusions: ONS compliance is evident in the significant improvement observed in muscle strength, anthropometric measurements, and quality of life data. The importance of addressing malnutrition in patients with GI cancer cannot be overstated. Therefore, it is imperative to maintain regular monitoring of their nutritional status and adherence to ONS. Research Sponsor: None.

742 Poster Session

Effect of PD-1/ PD-L1 and statin combination therapy on gastrointestinal toxicity related to immune checkpoint inhibitors and on survival. First Author: Yinghong Wang, The University of Texas MD Anderson Cancer Center, Houston, TX Background: Immune Checkpoint Inhibitor (ICI) therapy has greatly expanded its approval to treat a variety of malignancies with high efficacy. Inhibitors of programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) are two of the most common classes of ICI therapy. There has been significant research into medications that may have a synergistic effect with ICI therapy, notably statins due to their proapoptotic effect. The addition of statins to immunotherapy may also increase the risk of developing certain immune related adverse events (irAEs). We sought to investigate the effect of statin use on the development of gastrointestinal (GI) irAEs and on survival of patients on PD-1/L1 therapy. Methods: We conducted a review of select cancer patients at a tertiary cancer center who received PD-1/L1 inhibitors and statins between 2016 and 2022. The clinical characteristics and overall survival were compared to a control group who received PD-1/L1 inhibitors without statins. Results: A total of 823 patients were included in the statin group and compared to 11101 patients in the control group. In the statin group 707 received a PD-1 inhibitor, 86 received a PD-L1 inhibitor, and 30 received both checkpoint inhibitors. The included cancer types were lung cancer (44%), kidney cancer (26%), head/neck cancer (19%), and GI cancer (7.0%). The overall incidence of GI irAEs in patients receiving statins was 10.8%, which was comparable to patients without statin treatment (11.1%, p=0.83). In addition, statin treatment appeared to be associated with a more favorable survival in patients overall (p= 0.004) and also those with GI irAEs (p=0.047). Conclusions: Synergism between statins and PD-1/L1 inhibitors continues to be a developing field of interest. Our data showed the combination therapy's survival benefit without exacerbating GI toxicity, which warrants further investigation of this treatment strategy. Research Sponsor: None.

743 Poster Session

Role of proton pump inhibitors in immune checkpoint inhibitor colitis. First Author: Roshini Pradeep, Midwestern University GME Consortium Residency Program, Cottonwood, AZ Background: Proton pump inhibitors (PPIs) are known to be beneficial in symptomatic control of gastroesophageal reflux disease and gastritis which can be a common complication of various cancers specifically gastrointestinal (GI) cancers. Microscopic colitis development has been studied to be associated with PPI use. Immune checkpoint Inhibitor (ICI) colitis is a known adverse effect of Inhibitors of Programmed cell death 1 (PD-1) and its ligand (PD-L1). Previous studies have also shown use of PPIs and NSAIDs are common risk factors which can exacerbate ICI Colitis caused by Inhibitors of PD-1 and PD-L1. This study is designed to observe association of certain drugs especially PPIs in ICI colitis. Methods: This is a single center, retrospective, and observational study that investigated patients treated with PD-1 and PD-L1 Inhibitors for management of any type of cancer between January 2022-September 2023. A list of patients treated with PD-1 and PD-L1 inhibitors was obtained from Inpatient pharmacy records followed by retrospective chart review to look for symptoms of colitis and other medications used by each patient. Primary outcome was to observe the role of PPIs in ICI colitis. Secondary outcomes were to observe the number of patients with GI cancers on PPIs who developed colitis. We also observed the effect of NSAIDs use as a potential risk factor in the population with ICI colitis. Results: The data consisted of 93 patients of which 17 (18.3%) developed colitis. Among this population 13 (76.5%) was ICI colitis, 2 (11.7%) was diverticular colitis and 2 (11.7%) was Infectious colitis. PPI use was seen in 3 out of 13 patients (23%) with ICI colitis. Patients with any type of GI cancer who developed colitis was 5 (25%) and PPI use in ICI colitis was seen in 2 out of these 5 patients. NSAIDs use was seen in 3 (23%) patients with ICI colitis. Conclusions: We did not observe significant association between PPI use and ICI colitis. ICI use becoming increasingly common in oncologic population, larger studies may be needed to further evaluate risk factors associated with ICI colitis in this population. Research Sponsor: None.

744 Poster Session

Immune-related adverse events in patients with gastrointestinal cancer undergoing pembrolizumab monotherapy: A systematic review of clinical trials. First Author: Nikolas Naleid, Department of Internal Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH Background: Pembrolizumab, an immune checkpoint inhibitor targeting programmed death 1 (PD-1), is widely employed in the treatment of various gastrointestinal (GI) cancers. This systematic review aims to assess the spectrum and incidence of immune-related adverse events (irAEs) associated with pembrolizumab monotherapy in GI cancer patients. Methods: A comprehensive search of PubMed/MEDLINE was conducted to identify full-text articles of clinical trials investigating pembrolizumab monotherapy in GI cancer patients. Two independent authors reviewed the articles and extracted data, with discrepancies resolved by consensus. Primary endpoints included the incidence of grade 3 or higher irAEs and the treatment discontinuation rate due to irAEs. Secondary endpoints encompassed the incidence of any-grade irAEs and specific irAEs such as pneumonitis, colitis, hepatitis, myositis, myocarditis, nephritis, pancreatitis, peripheral neuropathy, skin toxicity, endocrine toxicity, infusion reactions, and deaths.

Results: After excluding duplicates and articles not meeting inclusion criteria, data extraction and analysis were performed on 25 selected articles. Common reasons for exclusion included concomitant use of chemotherapy or targeted therapy and trials involving non-GI cancer patients. The analysis included 2866 patients with a median age of 62 years, of which 29% were female.

Tumor types included colorectal (13%), esophagogastric (46%), hepatocellular carcinoma (25%), and others (16%). The aggregate incidence of grade 3 or higher irAEs was 8.7%, with reported rates ranging from 3% to 41% across different trials. The incidence of any grade irAEs varied from 39% to 98%. The treatment discontinuation rate due to irAEs was 6.8%. The most common grade 3 or higher irAEs were hepatitis (3.6%), pneumonitis (0.8%), and colitis (0.7%). irAE-related deaths were infrequent (0.9%). Detailed irAE data are summarized in the Background: Neurotoxicity is one of the most significant and disabling side effects of oxaliplatin (OX) and frequently limits the amount of OX that can be used. OX uptake by organic cation transporter 2 (OCT2) into mouse and rat dorsal root ganglia is a prerequisite for OXinduced peripheral neuropathy (OIPN). Preclinical data in rat and mouse models from our group showed that by inhibiting YES1, pre-treatment with dasatinib (D) inactivated OCT2 and prevented acute and chronic OIPN. A phase I trial is ongoing investigating addition of D prior to OX to prevent OIPN. Methods: This was a Bayesian Phase 1b dose-finding study with adaptive dose selection using efficacy-toxicity trade-offs in patients (pts) with GI cancers who are candidates for mFOLFOX6 6 bevacizumab [NCT04164069]. Pts received chemotherapy on day 1 and 15 schedule, every 28 days. D was administered at one of 2 dose levels -100mg or 140mg PO, given 24 hours and 30 mins prior to OX on C1D14, C1D15 respectively and repeated on C1D28 and C2D1. During cycle 1, pharmacokinetic and pharmacodynamic data was obtained at baseline, during, and up to 24 hours after D or OX administration. Recommended Phase 2 dose (RP2D) was defined as the lowest intermittent dose of D that affects serum biomarkers of OCT2, including methylnicotinamide (NMN) and creatinine, by $2-fold without influencing the clearance of oxaliplatin by $20%. CIPN20 questionnaire was completed prior to each dose of FOLFOX on screening through to C3D1. Weakly informative Jeffreys priors were used for response and toxicity probabilities, with the latter constrained to be increasing with dose. Results: 13 pts were screened. 5 pts enrolled in cohort 1 (D 100 mg), 2 in cohort 2 (D 140 mg) and 2 in cohort 3 (D 140mg). 6 pts were not evaluable for the efficacy and toxicity endpoints due to screen failure or early study discontinuation. 7 patients were evaluated for efficacy biomarkers and 6 pts were evaluated for both efficacy biomarkers and toxicity. There were no DLTs observed in any cohort. 4/7 pts had $2-fold increase in AUC of NMN, and 3/7 pts had $2-fold increase in AUC of creatinine. 6/7 pts had #20% change in the clearance of OX. Conclusions: Addition of D 100mg or 140mg to traditional FOLFOX regimen was safe and in the majority of pts appeared to alter serum biomarkers of OCT2 in a manner suggesting inhibition of OX uptake in the DRG. 140mg was the chosen RP2D. A randomized phase II study is planned using D to prevent OPIN.

747 Poster Session

A phase I/II trial investigating safety and efficacy of autologous TAC01-HER2 in relapsed or refractory solid tumors. First Author: Benjamin L. Schlechter, Dana Farber Cancer Institute/Brigham and Women's Hospital Cancer Center, Boston, MA Background: Despite therapeutic developments for patients with advanced HER2+ solid tumors, significant unmet medical needs still exist. The T cell antigen coupler (TAC) technology is an approach to modifying T cells ex vivo, which allows recognition and cytotoxicity of tumor cells by co-opting the natural T cell receptor. TAC T cells demonstrate a safer profile than chimeric antigen receptor T cells. TAC01-HER2 is an autologous T-cell product comprising T cells expressing HER2 TAC. Methods: The ongoing clinical trial (NCT04727151) is evaluating the safety and preliminary anti-tumor activity of TAC01-HER2 treatment of HER2+ solid tumors. Subjects undergo leukapheresis followed by low-intensity lymphodepletion chemotherapy prior to TAC01-HER2 infusion. In phase I dose escalation, TAC01-HER2 is administered at increasing doses (Cohorts 1-4) in adult subjects after $2 lines of therapy. Dose limiting toxicities (DLT) are assessed up to 28 days from TAC01-HER2 infusion. In Phase II, dose expansion groups will further evaluate the efficacy, safety, and pharmacokinetics of the optimal TAC01-HER2 dose in gastric/GEJ tumors. Results: As of 31 August 2023, 20 patients with solid tumors have been treated in Cohorts 1-4. Subjects had a median of 4 prior therapies (2-12) and all had maintained HER2 expression on central review at enrollment. Three subjects were HER2 1+ or 2+/FISH-. One DLT event of grade 3 (G3) pneumonitis has been reported in 1 subject in Cohort 4. No neurotoxicity has been reported. Most subjects treated at Cohorts 3-4 experienced cytokine release syndrome (CRS) which resolved with supportive therapy. Fifteen subjects have reported a total of 31 serious adverse events, with 1 G3 pneumonitis and 5 CRS (one G1, three G2 and one G3) related to TAC01-HER2. A 68.8% disease control rate (DCR) was observed in Cohorts 2-4 at first restaging after TAC01-HER2 infusion. For gastric/GEJ subjects of the same Cohorts, DCR was 85.7%. 3 months after TAC01-HER2 infusion, DCR was 30.8% for all subjects of Cohorts 2-4 and 28.6% for gastric/GEJ subjects. Two patients had a partial response (PR). At Cohort 4, a PR was observed in a subject with GEJ (HER2 2+, FISH+) with 100% reduction of target lesion. This patient had progressed on 4 prior lines of therapy including trastuzumab and trastuzumab deruxtecan. Conclusions: Treatment with TAC01-HER2 showed manageable safety and promising clinical activity in a heavily pre-treated cancer population. The recommended phase 2 dose was identified as dose level 4 (6-8 x 10 6 cells/kg). Clinical trial information: NCT04727151. Research Sponsor: Triumvira Immunologics.

748 Poster Session

Overall survival and long-term safety with ripretinib vs sunitinib in patients with advanced gastrointestinal stromal tumor previously treated with imatinib: Final analyses from INTRIGUE. First Author: John Raymond Zalcberg, School of Public Health and Preventative Medicine, Monash University, and Alfred Health, Melbourne, Australia

Background: Ripretinib is a switch-control tyrosine kinase inhibitor approved for patients (pts) with gastrointestinal stromal tumor (GIST) who received prior treatment with 3 or more kinase inhibitors, including imatinib. Sunitinib is approved for advanced GIST after imatinib failure. In the second interim analysis of overall survival (OS) from the phase 3 INTRIGUE study, the OS event rate was 41% in the allpatient (AP) intent-to-treat (ITT) population, and OS was similar between treatment arms in both the KIT exon 11 ITT and AP ITT populations. Here, we present the final OS and updated safety from INTRIGUE. Methods: INTRIGUE ( NCT03673501 ) is an open-label, phase 3 study of adults with advanced GIST who had disease progression on or intolerance to imatinib. Randomization was 1:1 to ripretinib 150 mg once daily (QD) or sunitinib 50 mg QD (4 weeks on/2 weeks off) and was stratified by KIT mutational status and imatinib intolerance. OS was a key secondary endpoint (the primary endpoint of progression-free survival was reported previously); final OS analysis was prespecified to occur with $200 and $145 events in the AP ITT and KIT exon 11 ITT populations, respectively. ). Treatment discontinuation was due to progressive disease (PD) by independent radiologic review (56%), PD by investigator (11%), clinical PD (6%), withdrawal of consent (6%), and adverse events (AEs; 5%). Fewer pts discontinued treatment due to AEs with ripretinib vs sunitinib (3% vs 6%). There were 211 OS events (47%) in the AP ITT population and 151 OS events (46%) in the KIT exon 11 ITT population. OS was similar with ripretinib vs sunitinib in the 2 ITT populations (Table ). Fewer pts had grade 3/4 treatment-emergent AEs with ripretinib vs sunitinib (43% vs 67%). Dose interruptions and reductions were lower with ripretinib vs sunitinib. Median treatment duration for ripretinib vs sunitinib was 7.9 vs 6.5 months. Conclusions: In the finalOS analysis from the INTRIGUE study, OS was similar between treatment arms. The safety profile remained consistent and more favorable for ripretinib vs sunitinib in pts with advanced GIST previously treated with imatinib. Clinical trial information: NCT03673501. Research Sponsor: Deciphera Pharmaceuticals, LLC.

Final OS analysis. 186s OTHER GI CANCER Visit meetings.asco.org and search by abstract for the full list of abstract authors and their disclosure information.

Oncolytic virus CF33-hNIS monotherapy for the treatment of gastrointestinal (GI) malignancies. First Author: Daneng Li, City of Hope National Comprehensive Cancer Center, Duarte, CA Background: CF33-hNIS is a novel chimeric DNA vaccinia virus engineered with the human sodium-iodide symporter (hNIS) gene. CF33-hNIS selectively replicates in tumor cells leading to cell lysis and the release of tumor-and virus-associated antigens stimulating antitumor immunity. Here, we report results of patients with GI malignancies enrolled on a first-in-human phase 1 ascending, multiple dose, safety and tolerability study of CF33-hNIS, administered intratumorally (IT) or intravenously (IV) in adult patients with metastatic or advanced solid tumors (MAST). Methods: The MAST study is evaluating the safety of CF33-hNIS administered IT or IV, alone or in combination with pembrolizumab in patients with advanced or metastatic solid tumors with $ 2 prior lines of therapy (NCT05346484). CF33-hNIS is administered in 21day cycles on C1D1 and C1D8, then D1 of each cycle thereafter. Pembrolizumab begins C2D1 for the combination groups and is administered Q3W. The co-primary endpoints are safety and to identify the recommended phase 2 dose. Secondary endpoints include objective response rate according to RECIST v1.1 and iRECIST, and to assess levels of viral replication via Single-Photon Emission Computerized Tomography (SPECT) with technetium-99. Results: As of Aug 2023, we report early results from seven patients with GI malignancies who received CF33-hNIS alone, including: colorectal cancer (3), bile duct (2), pancreatic (1) and hepatocellular carcinoma (1). The disease control rate is 86%. Notably one patient with cholangiocarcinoma, treated IT with 3.0x10 7 PFU, presented with pseudoprogression with a 49% increase in tumor burden after two cycles of therapy. By the 4 th cycle they achieved a complete response (CR) with no known recurrence. A second patient with bile duct cancer, who previously progressed on checkpoint blockade therapy, achieved stable disease for .5 months upon receiving IVadministered CF33-hNIS (3.0x10 7 PFU). Treatment-related adverse events for the CR patient included grade 1 fever and injection site All other patients experienced no treatmentrelated adverse events. SPECT analysis of the CR patient reveals intense levels of viral replication within the injected lesion and a concomitant increase in Th1 cytokines in cycle three that coordinated with tumor reduction. In-depth immunological changes in peripheral blood and on-treatment tumor biopsies will be presented. Conclusions: CF33-hNIS can replicate within cholangiocarcinoma lesions, as shown by SPECT imaging, and drive immunological changes known to promote antitumor immunity. CF33-hNIS monotherapy may be an effective and safe treatment option for GI malignancies, including cholangiocarcinoma, a rare disease with an unmet medical need. Treatment with CF33-hNIS monotherapy was well tolerated and the study has advanced to examine combination therapy with pembrolizumab. Clinical trial information: NCT05346484. Research Sponsor: Imugene Limited.

751 Poster Session

Association of plasma uracil concentration with 5-FU pharmacokinetics, dose-limiting toxicity, and DPYD genotype in patients with gastrointestinal cancer. First Author: Gabriel A. Brooks, Dartmouth Cancer Center, Lebanon, NH Background: Plasma uracil concentration .16 ng/mL is used in some countries as a screening test for DPD deficiency. We conducted this exploratory study to evaluate the association of uracil concentration with 5-FU exposure, toxicity, and DPYD genotype in patients without known DPD deficiency. The main hypothesis was that lower uracil concentration would be predictive of subtherapeutic 5-FU drug exposure (5-FU AUC , 20 mg*h/L) in patients treated with infusional 5-FU. Methods: The study prospectively enrolled patients with GI cancer who were receiving initial chemotherapy with a regimen containing a 46-hour 5-FU infusion initially dosed at 2400 mg/m 2 . Study candidates were screened for the DPYD *2A, *13 and c.2846A.T gene variants; variant carriers were excluded. Participants gave pretreatment fasting morning blood samples for determination of plasma uracil concentration and DPYD whole-gene sequencing. Plasma samples were collected at hour 45 of 5-FU infusion in chemotherapy cycles 1 and 2 for determination of 5-FU exposure, measured as the 5-FU AUC. We estimated a linear mixed-effects model to test the association of uracil concentration with 5-FU AUC, adjusting for cycle, sex, creatinine, and 5-FU infusion dose (in mg/m 2 ). Results: There were 29 evaluable participants with a median age of 64 years (range 41-81); nine (31%) were female. The most common cancer sites were colorectal (n = 15) and pancreatic (10). The median (IQR) plasma uracil concentration was 10.4 ng/mL (7.2, 12.6). Data for 5-FU AUC were available for 19 subjects in cycle 1 (median = 22.0 mg*h/L) and 27 subjects in cycle 2 (median = 19.3 mg*h/L). In the mixed-effects model, male sex was significantly associated with 5-FU AUC (beta = -12.0 [95% CI -17.2, -6.7], p ,0.001) but plasma uracil concentration was not (beta = 0.35 [-0.16, 0.86] , p=0.16). Holding other covariates constant, male sex was associated with a 29% decrease in 5-FU AUC (vs female) and plasma uracil concentration in the lowest quartile was associated with a 12% decrease in 5-FU AUC (vs highest quartile). Three of 29 participants (10%, all male) had uracil concentrations of .16 ng/mL, suggestive of DPD deficiency. The subject with the highest uracil concentration (23.1 ng/mL) had severe toxicity in cycle 1 (neutropenia, mucositis) requiring 5-FU dose reduction; whole gene sequencing identified a rare DPYD missense variant in this subject (c.2185G.A [p.A729T]). The other two subjects with uracil concentration .16 ng/mL did not have culprit DPYD gene variants and tolerated infusional 5-FU at 2400 mg/m 2 without early dose-limiting toxicity. Conclusions: Our findings suggest that male sex is more important than low pretreatment plasma uracil concentration as a predictor of risk for subtherapeutic 5-FU drug exposure. This result is consistent with prior evidence that men experience less 5-FU associated toxicity than women. Research Sponsor: American Cancer Society.

752 Poster Session

SBRT with ipilimumab and nivolumab to metastatic MSS colorectal and pancreatic cancer: A pooled analysis of four prospective phase II trials. First Author: Hannah Johnson Roberts, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA Background: The role of immunotherapy (IO) in microsatellite stable (MSS) pancreatic and colorectal cancer is limited. Stereotactic body radiation therapy (SBRT) is increasingly used in the limited metastatic setting, however its use with IO remains an area of investigation for both target response and overall systemic response. Here we evaluate the local failure rate of irradiated target lesions with and without IO. Methods: We pooled four prospective phase II single-arm studies of patients with metastatic MSS colorectal or pancreatic cancer treated with SBRT alone or with IO. Those in the first study (NCT01239381) received ablative liver SBRT to a maximum biologically effective dose (BED) of 48-100 Gy. Patients in the remaining studies received low dose SBRT to liver, lung, or nodal metastases with 24 Gy in 3 fractions to a BED of 43.2 Gy in combination with Ipilimumab and Nivolumab during the first (NCT04361162, NCT04575922) or second (NCT03104439) cycles. Local failure rates at the time of first progression were estimated by the cumulative incidence with non-target progression only and death as competing risks and compared using Gray's test. The best response at the target was measured with the RECIST 1.1 criteria using the largest reduction in target size during follow up. Fisher's exact test was used to compare objective response (ORR) and disease control rates (DCR), while the Wilcoxon rank sum test was performed to compare target size and percentage of tumor reduction. Results: Across all four studies there were 154 evaluable patients including 50 who received ablative SBRT and 104 patients who received low dose SBRT with IO. There were 92 patients with colorectal and 62 with pancreatic cancer. Median target size was 3.7 cm in the ablative SBRT group and 2.8 cm in the IO group (P=0.04). The 6month, 1-year, and 2-year local failure rates were 10%, 18%, and 20% respectively following ablative SBRT and 24%, 25%, and 26% following low dose SBRT with IO (P=0.32). The ORR was 50.0% with SBRT alone and 23.1% with the addition of IO (P=0.001). There was no significant difference in the DCR (80.0% vs. 68.3%, P=0.18). The percent decrease in size was significantly higher in those with ablative SBRT (median -53.0% vs. -10.6%, p=0.02). There was no difference in the percent tumor response with respect to primary tumor type (P=0.13), KRAS (P=0.11) or TP53 (P=0.27) status. Conclusions: Despite the use of low dose SBRT with immune checkpoint inhibitors, there was no significant difference in local failure rates compared to ablative SBRT. Ablative SBRT dosing yielded a significantly higher depth of response. As clinical and preclinical studies suggest liver metastases are less responsive to IO, understanding dose and fractionation schemas for optimal local control is critical. Further studies are needed to explore the radiation dose with regards to local control when delivered with IO.

753 Poster Session

Efficacy of biomarker-matched therapy in clinical trials for advanced gastrointestinal cancers: A pooled analysis of SCRUM-Japan studies. First Author: Tadayoshi Hashimoto, Department of Gastroenterology and Gastrointestinal Oncology/Translational Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan Background: We conduct the SCRUM-Japan MONSTAR-SCREEN, a nationwide molecular profiling project to facilitate the enrollment of patients with advanced solid tumors into matched clinical trials based on identified biomarkers. Here, we investigated clinical outcomes of patients with gastrointestinal cancers in this project. Methods: The SCRUM-Japan GI-SCREEN was launched for gastrointestinal cancers in 2015, followed by GOZILA, MONSTAR-SCREEN-1, and MONSTAR-SCREEN-2 for advanced solid tumors. The used profiling assay for genomic alterations was Oncomine Comprehensive Assay for tumor tissue in GI-SCREEN, Guardant360 for plasma in GOZILA, FoundationOne CDx for tissue and FoundationOne Liquid CDx for plasma in MONSTAR-SCREEN-1, and CARIS MI Profile for tissue in MONSTAR-SCREEN-2. Patients were treated in clinical trials or practice based on identified biomarkers. We analyzed data from patients with gastrointestinal cancers in this project. Results: Of 11,408 patients enrolled in our project as of May 22, 2023, 555 (5.0%) were enrolled in matched clinical trials based on identified biomarkers. The major cancer types that had matched clinical trials included colorectal (63.2%), biliary tract (12.4%), gastric (n=9.2%), esophageal (n=6.5%), and pancreatic cancer (n=4.7%). The objective response rate (ORR), median progression-free survival, and median overall survival (OS) for patients in matched trials were 27.8% (95% CI, 24.0% to 31.9%), 3.0 months (95% CI, 2.8 to 3.7 months), and 14.4 months (95% CI, 13.0 to 16.1). The major treatment lines in which investigational drugs were administered were third (24.6%) and fourth (16.0%) line. Evaluating by each drug target given to at least 20 patients, therapies targeting HER2 had the highest ORR of 46%, followed by PD-1/PD-L1 (33%), BRAF (30%), and MEK (28%). Antibody-drug conjugates demonstrated the highest ORR with 48.8%, followed by monoclonal antibodies at 37.7% and small molecule inhibitors at 23.0%. Overall, patients who received matched therapy in clinical trials or practice had significantly longer OS than those who did not (hazard ratio, 0.76; 95% CI 0.69 to 0.84; P ,0.01). Conclusions: Our nationwide molecular profiling project has facilitated the enrollment of patients with advanced gastrointestinal cancers in clinical trials. Furthermore, it demonstrated a survival benefit by providing patients matching targeted therapy. Research Sponsor: None.

Is lymph node metastasis an event indicating an advanced gastrointestinal stromal tumor? First Author: Peng Zhang, Wuhan Union Hospital, Wuhan, Hubei, China Background: The clinicopathological features and prognosis of gastrointestinal stromal tumors (GISTs) with lymph node metastasis remain controversial owing to their low incidence. A multicenter retrospective cohort study was conducted to compare the clinicopathological features and oncologic outcomes of GIST with and without lymph node metastases. Methods: The medical records of patients with GISTs in 16 large medical centers in China from January 2014 to December 2020 were reviewed. Patients were divided into three groups: no metastasis, lymph node metastasis without distant metastasis, and distant metastasis without lymph node metastasis. Propensity score matching (PSM) was performed to reduce confounding factors. Results: A total of 1109 cases of primary GIST were included in this study, comprising 607 males (54.7%) and 502 females (45.3%), with a mean age of 56.6611.9 years. There were 1024 patients (92.3%) with no lymph node metastasis after surgery, and 85 patients (7.7%) had lymph node metastasis. Compared to that in GIST without lymph node metastasis, the proportion of non-gastric GIST was higher in GIST with lymph node metastasis (52.9% vs. 40.7%) with a larger tumor diameter (.10 cm: 36.5% vs. 18.1%) and more patients with distant metastasis (11.8% vs. 3.5%). Tumor location not in the stomach, the largest tumor diameter, and distant metastasis were independent risk factors for GIST with lymph node metastasis (all P , 0.05). After PSM, 96, 48, 24 patients comprised no metastasis, lymph node metastasis without distant metastasis, and distant metastasis without lymph node metastasis, respectively. The relapse-free survival (RFS) of the lymph node metastasis group was comparable to that of the distant metastasis group without lymph node metastasis (P = 0.368) and significantly inferior to that of no metastases (P = 0.042). Conclusions: The prognosis of patients with GIST with lymph node metastasis was comparable to that of patients with distant metastasis and significantly worse than that of patients without metastasis. Lymph node metastasis may be an advanced event in GIST. Research Sponsor: None.

755 Poster Session

Comprehensive genomic profiling of squamous cell carcinoma of unknown primary presenting with liver metastases. First Author: Hannah Ruth Robinson, University of Colorado Cancer Center, Aurora, CO Background: Carcinomas of unknown primary (CUPs) are comprised of metastatic cancers for which a primary tumor of origin cannot be identified despite a full diagnostic workup. They frequently present with liver metastases, which portend a poor prognosis. Strategies employing comprehensive genomic profiling (CGP) to identify targeted treatments for CUPs have shown potential. Despite this, the molecular landscape of squamous cell carcinomas of unknown primary (SCCUPs) remains poorly defined. This study describes the results of CGP testing in patients with SCCUPs identified in the Foundation Medicine, Inc. database, with a focus on those with liver involvement. Methods: Cases of SCCUPs with FoundationOne CDx (F1CDx) assay results were identified based on a reported diagnosis of CUP and the presence of SCC histology.

Cases then underwent central pathologist review and were excluded if a known primary site could be determined based on histology and disease location. Cases with liver involvement were selected based on the site of tissue biopsy. Genomic analyses of identified cases were assessed using the FoundationCORE database. Results: Sixtynine cases of SCCUP presenting with liver involvement were identified. Alterations were observed in 102 of 324 (31.5%) genes evaluated by the F1CDx assay in at least 1 patient. The most frequently altered genes were TP53 (66.7%), CDKN2A (33.3%), CDKN2B (23.2%), KRAS (21.7%; 0% G12C), PIK3CA (18.8%), NFE2L2 (11.6%), SOX2 (11.6%), M2M2 (10.1%), and MTAP (10.1%). No patients had microsatellite instability-high disease, only 6 (8.7%) patients had a tumor mutational burden (TMB) $ 10, and 11 (15.9%) patients had evidence of HPV infection. Among 33 patients with available PDL-1 testing results, 7 (21.2%) had high-positive expression. An additional 374 cases of SCCUP were identified with involvement outside of the liver. Compared to these cases, patients presenting with liver involvement had less genomic alterations per tumor (5.10 vs 6.71, p=0.005), and were less likely to have TMB $ 10 (8.7% vs 38.0%; odds ratio [OR] 0.16, p,0.001). KRAS mutations were observed in 21.7% of those presenting with liver metastases compared to 8.3% of other SCCUP patients (OR 3.07, p=0.07). Conclusions: SCCUPs presenting with liver metastases had reduced numbers of genomic alterations and decreased TMB compared to other SCCUPs, suggesting these tumors may be less likely to respond to immunotherapy. Despite this, 36.2% of these patients had at least one alteration that could potentially guide targeted treatment decisions including entry into biomarkerdriven clinical trials. Interestingly, there was a trend toward increased KRAS alterations in those with liver metastases. To our knowledge, this is the first report that describes the genomic landscape of SCCUPs presenting with liver metastases. Research Sponsor: None.

756 Poster Session

Clinical validation of Northstar Response, a novel methylated ctDNA therapy response monitoring assay in patients with advanced GI cancer undergoing active treatment. First Author: Ilyas Sahin, University of Florida/UF Health Cancer Center, Gainesville, FL Background: ctDNA is a non-invasive way to holistically assess the tumor. Several assays developed for therapy response monitoring rely on variant allele frequencies to detect scarce somatic variants in the blood. In contrast, methylated ctDNA measurement has shown promise as a treatment monitoring biomarker without requiring a tumor biopsy, yet accuracy is limited in ability to precisely quantify the amount of methylation present in the ctDNA. The CLIA-approved Northstar Response assay (BillionToOne, Inc.) quantifies on average 90 methylated loci, a 10-fold increase in signal over the average tissueinformed assays. Methods: This prospective, observational study assesses the clinical validity of Northstar Response, a quantitative methylated ctDNA therapeutic response monitoring assay that does not require prior tumor tissue. A cohort of 100 advanced cancer patients with a variety of GI malignancies submit serial ctDNA measurements in a blinded fashion. Use of tumor-informed ctDNA across gastrointestinal cancers. First Author: Matthew Reilley, Division of Hematology/Oncology, University of Virginia, Charlottesville, VA Background: In colorectal cancer (CRC), the use of ctDNA for the purpose of early recurrence detection and prognostication is established, and multiple studies are testing its utility for guiding adjuvant therapy decisions. Tumor informed testing can be performed in clinical situations where adequate tissue is available for next-generation sequencing (NGS). Increasingly, ctDNA testing is being used clinically for colorectal cancer patients and other gastrointestinal (GI) cancers when there is an appropriate clinical scenario and adequate tumor tissue is available for sequencing. Methods: We identified GI cancer patients treated at our institution where Signatera (Natera) testing was ordered and performed between 2020 -2023. We included all patients for whom testing was ordered. Then, among patients with any result further analyzed results by disease type, stage, and results. We examined clinical rationale for testing and whether results informed subsequent decisions. Results: A total of 99 GI cancer patients for whom ctDNA testing was ordered were identified. 80 patients had at least 1 ctDNA result including 68 colorectal patients and 12 other GI cancers (anal, bile duct, esophagogastric, pancreatic, and small bowel). Among patients with measurable ctDNA, at the most recent testing timepoint 16 had levels that met criteria for positive detection, while 64 were undetectable. Most commonly, testing was ordered in stage II/III CRC patients for post-operative surveillance. Other clinical use scenarios included 1) surveillance/ treatment monitoring in oligometastatic CRC, 2) surveillance in non-metastatic esophagogastric cancer, 3) treatment monitoring in MSI-H/immunotherapy sensitive GI cancers. For at least 18 patients, results were a factor in shared clinical decision making between patients and providers. Conclusions: We found ctDNA monitoring is most commonly used in the adjuvant setting for CRC patients which is best supported by existing studies. Our data demonstrates that tumor informed testing can be successful in other GI cancers for both surveillance and therapy monitoring. Given the broad and rapid adoption of this technology, there needs to be continued efforts for both prospective validation studies and retrospective real world studies to guide clinical practice.

759 Poster Session

Real-world analyses of BRAF alterations in patients with non-colorectal gastrointestinal cancers. First Author: Amit Mahipal, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH Background: BRAF V600E mutations are present in 5-10% of patients with advanced colorectal cancer (CRC) and associated with poor prognosis. Recently, there was tumor agnostic FDA approval of dabrafenib + trametinib for BRAF V600E mutated solid tumors. However, the frequency of BRAF alterations (BRAF alt), especially non-V600E, in other gastrointestinal (GI) cancers are not well described. This study characterizes BRAF alt in CRC vs other GI cancers (non-CRC). Methods: De-identified records from 51,560 patients diagnosed with GI cancers were retrospectively analyzed from the Tempus database. The molecular landscape including presence of pathogenic/likely pathogenic BRAF alt was evaluated by panel-based tissue DNA, RNA or ctDNA NGS sequencing (Tempus Labs, Inc.). The frequency of BRAF alt, co-mutations, MSI, TMB and MMR were compared between CRC and (non-CRC) by Chi-squared/Fisher's Exact or Wilcoxon rank-sum tests. False-discovery rate correction was used for multiple testing. Results: BRAF alt were identified in 8.9% of CRC and 2.2% of non-CRC cohort. BRAF alt frequency varied by tumor type with the highest observed in colon (11%), jejunum (9.6%), intrahepatic bile duct (5.3%), rectal (4.5%), and ampulla of vater (4.5%) and lower in esophageal (0.9%) and gastric (1.6%). BRAF alt CRC had higher frequency of females (57% vs 45%, p ,0.001) and older age at diagnosis (67 vs 66 yrs, p=0.029) compared to non-CRC group. Race was also significantly different, with white patients being more predominant in both groups (85% CRC,77% non-CRC). Among the BRAF alt, fusions (12% vs 2.2%, p ,0.001) and amplifications (3.1% vs 0.3%, p ,0.001) were higher in non-CRC vs CRC (Table ). BRAF V600E was most common in all GI tumors, but higher in CRC vs non-CRC (75% vs 27%, q,0.001). Mutations higher in non-CRC vs CRC (q,0.009) included class II (G469A, K601E, BRAF-SND1, and BRAF amplification) and class III (D594N & N581S) BRAF alt. BRAF co-occurring mutations in CRC were TP53 (70%), APC (42%), RNF43 (30%), SMAD4 (22%), and PIK3CA (21%), and in non-CRC: TP53 (52%), CDKN2A (32%), CDKN2B (20%) SMAD4 (17%) and MTAP (16%). Among tissue samples, MSI-H (30% vs 4.%, p ,0.001) and TMB-H $10 mut/MB (32% vs 6.7%, p ,0.001) were more frequent in BRAF alt CRC vs non-CRC. Conclusions: Meaningful differences were found between the groups in terms of demographics, frequency, and type of BRAF alt and co-occurring mutations. In particular, certain BRAF fusions were present in a higher proportion of other GI cancers and could be an important therapeutic target for this patient population. Research Sponsor: None.

Frequency of BRAF GOF alt types by GI cohort.

760 Poster Session

Single cell transcriptomic profiling of appendiceal adenocarcinoma to identify rare tumor cells and a myeloid-enriched tumor microenvironment (TME).

First Author: Betul Beyza Gunes, Heidelberg University, Mannheim, Germany Background: Appendiceal adenocarcinoma (AA) is a rare malignancy with distinct clinical and molecular characteristics compared to colorectal cancer (CRC). Currently there is little knowledge regarding how tumor cells from AA interact with the tumor microenvironment (TME). In this study, we performed single cell RNA sequencing (scRNAseq) on metastatic AA tumors taken from three patients undergoing curative intent surgical resection. Methods: After obtaining informed consent, tumor tissue from three patients with AA and one patient with CRC undergoing cytoreductive surgery at the MD Anderson Cancer Center (MDACC) was harvested and dissociated into single cell suspension for scRNAseq; libraries were prepared with '5 sequencing (10X Genomics). Bulk RNA sequencing from 19 additional patients with AA was available as a validation cohort. Results: scRNAseq analysis of a cohort of 3 patients with AA, 1 with CRC, and 12 healthy control samples identified 39,451 evaluable single cells after filtering and doublet removal. Separating cells into immune, stromal, and epithelial compartments identified that epithelial cells are rare in AA tumors. On average, AA constituted 62% stroma, 36% immune and only 2% epithelial cells, in contrast to healthy appendix (46% immune, 29% epithelial, 25% stroma). Sub-classification of immune cells revealed enrichment of myeloid cells in AA tumors (67% myeloid, 27% T, 5% B and 1% plasma B cells). This is in contrast to healthy appendix tissue (44% T, 26% plasma B, 22% B, 6% myeloid and 2% mast cells). In CRC, the majority of immune cells from the CRC sample were T cells (69%). These single cell data were used to improve deconvolution of bulk RNAseq, allowing for evaluation of TME contribution to transcription using bulk RNAseq data. Analysis of tumors from 19 patients with AA confirmed myeloid predominance in AA tumors. We performed pseudobulk differential expression analysis between compartments comparing CRC and AA which identified significant differences between compartments. Gene set enrichment analysis enabled identification of organized compartment specific changes.

764 Poster Session

Characterizing the rare abdominal neoplasms of peritoneum, retroperitoneum, and overlapping sites of peritoneum and retroperitoneum: A review of NCDB database. First Author: Baqir Jafry, UT Southwestern Medical Center, Dallas, TX Background: The tumor characteristics of the rare abdominal tumors including peritoneum (PT), retroperitoneum (RT) and overlapping sites of peritoneum and retroperitoneum (OT) remain unexplored. Methods: From the National Cancer Database, we identified all patients who were diagnosed with tumors in PT, RT or OT from 2004 to 2016. We evaluated the incidence of each tumor across time and compared population characteristics of each of these tumors. Results: We identified a total of 47300 patients -22090 had PT, 11837 had RT and 13373 had OT. The mean age of PT was 66.9 while that of RT and OT was 61.2 and 68.1 respectively. All three cancers had a higher percentage of females compared to males (93.8% for peritoneum; 50.4% for retroperitoneum; 50.6% for overlapping sites), whites (88.8% for PT; 83.6% for RT; 81.5% for OT), insured patients (97.8% for PT; 96.2% for RT; 96% for OT) and patients without any existing comorbidities (75.9% for PT; 77.5% for RT; 67.7% for OT). The most common histology was adenocarcinoma in OT, leiomyosarcoma in RT, serous epithelial carcinoma among the PT population.

TPS765 Trials in Progress Poster Session

Evaluating novel therapies and circulating tumor DNA (ctDNA) as a marker of response in curatively treated gastrointestinal cancers with microscopic residual disease. First Author: Reetu Mukherji, Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC

Background: ctDNA has emerged as a novel tool that can identify the earliest sign of relapse (MRD) after curative therapies with specificities of 93-100%, positive predictive values over 98%, and median lead times of 8-9 months before radiographic relapse. ctDNA has allowed us to identify a "new stage" of high-risk patients (pts) with no evidence of disease radiographically (rNED) and MRD who lack guideline-directed treatment (tx) strategies as, traditionally, they wait for radiographic progression of disease (POD) before starting therapies. Treating MRD is a promising strategy supported by observational studies where ctDNA clearance is linked with improved survival and on-tx ctDNA kinetics predict drug efficacy. We designed a pilot investigator-initiated trial to 1) determine the feasibility of using a surrogate marker, ctDNA, as a rapid signal for positive therapeutic activity and 2) obtain pilot data on the efficacy of a novel combination therapy (atezolizumab [A] + bevacizumab [B] ) in eradicating MRD in previously curatively treated pts with GI cancers. Methods: We will enroll 20 pts with anystage GI cancers divided over 4 cohorts (n=5 colorectal [CRC], n=5 hepatocellular/biliary tract carcinoma, n=5 gastric, n=5 pancreatic adenocarcinoma) who have a positive Signatera ctDNA test and rNED any time after completing standard curative-intent therapies. Pts are treated with A 1200 mg IV + B 15 mg/kg IV on day 1 of a 21-day cycle for up to 1 year with imaging every 12 weeks and serial ctDNA testing every 3 weeks. Co-primary endpoints are rates of pt enrollment in 12 months and rates of ctDNA responses at a 12-week landmark after tx initiation. Pts with ctDNA POD (ctDNA doubling on each of 2 sequential tests, any rate of rise in 3 sequential tests, or radiographic relapse) will stop while those with ctDNA complete response (CR; clearance on 2 sequential tests + ongoing rNED) or ctDNA partial/stable response (PR; not ctDNA CR or POD + ongoing rNED) will continue tx. Each cohort's Bayesian predictive probability of positive therapeutic activity will be calculated. If at least 60% of a cohort experiences ctDNA CR, it will be expanded by 5 pts. This scenario is equivalent to Simon's 2stage Minimax design testing a null hypothesis of 20% CR vs. an alternative hypothesis of at least 60% CR at 5% alpha with 80% power. If at least 5/10 pts in an expanded cohort experience ctDNA CR, this will generate interest in developing a larger confirmatory trial to evaluate pt survival outcomes with A+B and ctDNA as a surrogate for survival. Secondary endpoints are toxicity and reasons for enrollment failure. Exploratory endpoints are associations between ctDNA conversion and disease-free survival, tumor whole exome sequencing data, and peripheral blood immune profiles collected at baseline and on tx. Enrollment began in Q1 2023. 4 pts are enrolled in the CRC cohort. Clinical trial information: NCT05482516. Research Sponsor: Genentech Inc; Natera, Inc.

TPS766 Trials in Progress Poster Session

Peak study: A phase 3, randomized, open-label multicenter clinical study of bezuclastinib (CGT9486) and sunitinib in combination versus sunitinib in patients with gastrointestinal stromal tumors (GIST). First Author: Michael C. Heinrich, Oregon Health & Science University Knight Cancer Institute, Portland, OR Background: Imatinib is the worldwide standard for first-line therapy of advanced KITmutant GIST. However, secondary resistance mutations in the KIT ATP-binding domain (exons 13, 14), activation loop (exons 17, 18), or both develop and result in loss of imatinib-sensitivity. While no single tyrosine kinase inhibitor (TKI) inhibits all KIT mutations, the combination of bezuclastinib + sunitinib targets commonly occurring primary (exons 9, 11) and secondary (exons 13, 14, 17, and 18) KIT mutations. In a Phase 1/2 clinical study, pts with relapsed and/or refractory GIST and a median of 3 prior lines of therapy treated with bezuclastinib + sunitinib (n=15) experienced clinical benefit and an acceptable safety profile, warranting further evaluation in a randomized trial. Methods: Peak (NCT05208047) is a global, randomized, open-label, multi-part Phase 3 study evaluating the efficacy and safety of bezuclastinib + sunitinib versus sunitinib as second-line treatment in adult pts who were intolerant to imatinib or whose tumors had imatinib-resistance. The lead-in portion, to test a new formulation of bezuclastinib, (Part 1) has completed enrollment. Based upon PK and safety, a dose of bezuclastinib 600 mg QD + sunitinib 37.5 mg QD has been determined for Part 2 of the Peak study. Part 2 will enroll ~388 pts to be randomized (1:1) to bezuclastinib 600 mg QD + sunitinib 37.5 mg QD or sunitinib 37.5 mg QD alone. Key inclusion: .1 measurable lesion per modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1, Eastern Cooperative Oncology Group Performance Status 0-2, adequate organ function, and prior imatinib therapy (no other prior therapy). Key exclusion: PDGFR mutations or succinate dehydrogenase deficiency, clinically significant cardiac disease, and use of strong CYP3A4 inhibitors or inducers. The primary endpoint is progression-free survival (PFS) confirmed by blinded independent central review per mRECIST v1.1. Additional efficacy (including overall survival and objective response rate) and safety endpoints will be evaluated. Clinical trial information: NCT05208047. Research Sponsor: Cogent Biosciences.

190s OTHER GI CANCER Visit meetings.asco.org and search by abstract for the full list of abstract authors and their disclosure information.

|||Rate of Completion (95% CI)||||| |---|---|---|---|---|---|---|

||LEP||||Hazard Ratio||

|Cologuard|EP 0.523 (0.509,0.537) 0.617 (0.603,0.631) 0.703 (0.691,0.716)|Reference|-||||

|Completion|||||||

||LEP|0.41 (0.339,0.495) 0.449 (0.377,0.535) 0.502 (0.428,0.587) 0.66(0.51,0.85)|0.41 (0.339,0.495) 0.449 (0.377,0.535) 0.502 (0.428,0.587) 0.66(0.51,0.85)|0.41 (0.339,0.495) 0.449 (0.377,0.535) 0.502 (0.428,0.587) 0.66(0.51,0.85)|0.41 (0.339,0.495) 0.449 (0.377,0.535) 0.502 (0.428,0.587) 0.66(0.51,0.85)|0.41 (0.339,0.495) 0.449 (0.377,0.535) 0.502 (0.428,0.587) 0.66(0.51,0.85)|

|Other CRC|EP 0.009 (0.007,0.012) 0.015 (0.012,0.019) 0.025 (0.021,0.03)|Reference|-||||

|Screening|||||||

||LEP|0.02 (0.006,0.06)|0.026 (0.01,0.069) 0.033 (0.014,0.078)|1(0.4,2.5)|0.993||

||Asian or Pacific|Black|Hispanic|Non-Hispanic| |---|---|---|---|---|

||Islander (n=326)|(n=129)|(n=350)|White (n=815)|

|Model 1: Unadjusted|1.19 (0.92-1.55)|0.95 (0.63-1.42)|1.30 (1.01-1.67)|1.00|

|Model 2: Model 1 +|1.19 (0.92-1.55)|0.96 (0.64-1.44)|1.30 (1.01-1.68)|1.00|

|age & sex|||||

|Model 3: Model 2 +|0.92 (0.70-1.21)|0.97 (0.65-1.46)|1.41 (1.09-1.83)|1.00|

|comorbidities|||||

|Model 4: Model 3 +|0.90 (0.68-1.19)|0.96 (0.63-1.45)|1.40 (1.07-1.83)|1.00|

|socioeconomic data|||||

|Model 5: Model 4 +|0.85 (0.64-1.12)|0.88 (0.58-1.33)|1.14 (0.87-1.49)|1.00|

|stage at diagnosis|||||

|Model 6: Model 5 +|0.85 (0.64-1.13)|0.88 (0.58-1.34)|1.20 (0.91-1.58)|1.00|

|tumor factors|||||

|Model 7: Model 6 +|0.82 (0.62-1.09)|0.78 (0.51-1.18)|1.08 (0.82-1.42)|1.00|

|treatment factors|||||

||CP||| |---|---|---|---|

||Users|CP Non-Users||

|Variable|N=102|N=194|p|

|Personal h/o LS cancer||||

|Yes (n=157)|52 (33)|105 (67)|p=0.61|

|No (n=139)|50 (36)|89 (64)||

|Gene mut||||

|MLH1 (n=60)|22 (37)|38 (63)|p=0.49|

|MSH2 (n=86)|29 (34)|57 (66)||

|MSH6 (n=85)|31 (36)|54 (64)||

|PMS2 (n=46)|17 (37)|29 (63)||

|Unsure (n=19)|3 (16)|16 (84)||

|Male (n=47)|12 (26)|35 (74)|p=0.16|

|Female (n=249)|90 (36)|159 (64)||

|Inconvenience (1=low, 10=high)|1.32 (0.90)|1.90 (1.89)|p=0.02|

|Side effects (1=low, 10=high)|2.30 (2.16)|3.61 (3.04)|p=0.0008|

|Reassurance (1=low, 10=high)|5.68 (2.41)|3.93 (2.49)|p,0.0001|

|Likelihood of recommending|7.57 (2.09)|4.49 (2.74)|P,0.0001|

|||||||||.4% vs 19.2%, OR=1.4, 95%|.4% vs 19.2%, OR=1.4, 95%|.4% vs 19.2%, OR=1.4, 95%| |---|---|---|---|---|---|---|---|---|---|---|

|CI=0.76-2.6; P=0.27). Restricting to only high-risk patients (poorly differentiated, LN-positive, and/or|CI=0.76-2.6; P=0.27). Restricting to only high-risk patients (poorly differentiated, LN-positive, and/or|CI=0.76-2.6; P=0.27). Restricting to only high-risk patients (poorly differentiated, LN-positive, and/or|CI=0.76-2.6; P=0.27). Restricting to only high-risk patients (poorly differentiated, LN-positive, and/or|CI=0.76-2.6; P=0.27). Restricting to only high-risk patients (poorly differentiated, LN-positive, and/or|CI=0.76-2.6; P=0.27). Restricting to only high-risk patients (poorly differentiated, LN-positive, and/or|CI=0.76-2.6; P=0.27). Restricting to only high-risk patients (poorly differentiated, LN-positive, and/or|CI=0.76-2.6; P=0.27). Restricting to only high-risk patients (poorly differentiated, LN-positive, and/or|CI=0.76-2.6; P=0.27). Restricting to only high-risk patients (poorly differentiated, LN-positive, and/or|CI=0.76-2.6; P=0.27). Restricting to only high-risk patients (poorly differentiated, LN-positive, and/or|CI=0.76-2.6; P=0.27). Restricting to only high-risk patients (poorly differentiated, LN-positive, and/or|

|T4, n=205), similar results were observed with 18.4% (n=17) relapsed without AC vs 19.4% (n=22)|T4, n=205), similar results were observed with 18.4% (n=17) relapsed without AC vs 19.4% (n=22)|T4, n=205), similar results were observed with 18.4% (n=17) relapsed without AC vs 19.4% (n=22)|T4, n=205), similar results were observed with 18.4% (n=17) relapsed without AC vs 19.4% (n=22)|T4, n=205), similar results were observed with 18.4% (n=17) relapsed without AC vs 19.4% (n=22)|T4, n=205), similar results were observed with 18.4% (n=17) relapsed without AC vs 19.4% (n=22)|T4, n=205), similar results were observed with 18.4% (n=17) relapsed without AC vs 19.4% (n=22)|T4, n=205), similar results were observed with 18.4% (n=17) relapsed without AC vs 19.4% (n=22)|T4, n=205), similar results were observed with 18.4% (n=17) relapsed without AC vs 19.4% (n=22)|T4, n=205), similar results were observed with 18.4% (n=17) relapsed without AC vs 19.4% (n=22)|T4, n=205), similar results were observed with 18.4% (n=17) relapsed without AC vs 19.4% (n=22)|

|relapsed with AC (OR=1.06, 95%CI=0.52-2.15; P=0.85). AC was also not associated with improved RFS|relapsed with AC (OR=1.06, 95%CI=0.52-2.15; P=0.85). AC was also not associated with improved RFS|relapsed with AC (OR=1.06, 95%CI=0.52-2.15; P=0.85). AC was also not associated with improved RFS|relapsed with AC (OR=1.06, 95%CI=0.52-2.15; P=0.85). AC was also not associated with improved RFS|relapsed with AC (OR=1.06, 95%CI=0.52-2.15; P=0.85). AC was also not associated with improved RFS|relapsed with AC (OR=1.06, 95%CI=0.52-2.15; P=0.85). AC was also not associated with improved RFS|relapsed with AC (OR=1.06, 95%CI=0.52-2.15; P=0.85). AC was also not associated with improved RFS|relapsed with AC (OR=1.06, 95%CI=0.52-2.15; P=0.85). AC was also not associated with improved RFS|relapsed with AC (OR=1.06, 95%CI=0.52-2.15; P=0.85). AC was also not associated with improved RFS|relapsed with AC (OR=1.06, 95%CI=0.52-2.15; P=0.85). AC was also not associated with improved RFS|relapsed with AC (OR=1.06, 95%CI=0.52-2.15; P=0.85). AC was also not associated with improved RFS|

|(HR=1.2, 95%CI=0.63-2.2, P=0.59). Conclusions: Mucinous|Goblet|||Colonic|||||||

|||||Overall|||Overall|||Overall|

|||RelapseÈ Relapse.|P-value RelapseÈ Relapse.|P-value RelapseÈ Relapse.|P-value||||||

|Grade G1|8, 27%|22|0.87|0|10|0.3|0|1|0.001||

||G2 16, 25%|48||0|26||1, 3%|31|||

||G3|9, 30%|21||6, 8%|69||4, 57%|3||

|Stage I, II 22, 23%|72|0.3|3, 3%|87|0.002|2, 7%|28|0.1|||

||III 10, 38%|16||2, 8%|24||3, 27%|8|||

|pT|T2|1, 10%|9|0.1|0|2|0.2|1, 50%|1|0.2|

||T3 12, 20%|47||3, 4%|81||2, 9%|21|||

||T4 19, 37%|32||4, 11%|31||2, 12%|15|||

|||Outcome relative to FIT 50 (4)||| |---|---|---|---|---|

|Total Colonoscopies (millions)|0.33|0.56|9.87|10.68|

|Total CRC cost, $ (billions)|0.31|0.66|2.24|2.48|

|CRC Management cost, $ (billions)|-0.76|-1.18|-3.52|-4.04|

|Incidence|-11,983|-18,345|-66,224|-74,252|

|Mortality|-5,218|-8,088|-14,648|-17,868|

|HALY gained|96,105|157,007|228,960|314,955|

|Incremental cost per HALY, $|3,259|4,209|9,776|7,881|

||Pre-||Post-|| |---|---|---|---|---|

|Question|Course||Course||

|Patient feelings about trial search (one word coded)|N|%|N|%|

|Negative|38|88%|4|17%|

|Neutral|2|5%|3|13%|

|Positive|3|7%|17|71%|

||N|Avg|N|Avg|

|Preparedness to find a trial?|44|2.1|24|3.8|

|Likelihood to pursue a trial?|44|3.9|24|4.0|

||Total Cohort|3 Months CAPOX|6 Months FOLFOX or| |---|---|---|---|

|Male|254 (56.2)|119 (52.7)|132 (60.6)|

|Age (years):||||

|£70|314 (69.5)|147 (65.0)|162 (74.3)|

|> 70|138 (30.5)|79 (35.0)|56 (25.7)|

|Urban setting|228 (50.4)|106 (46.9)|119 (54.6)|

|Tumor location:||||

|Right colon|214 (47.3)|108 (47.8)|102 (46.8)|

|Left colon|207 (45.8)|102 (45.1)|101 (46.3)|

|Rectal|31 (6.9)|16 (7.1)|15 (6.9)|

|Grade:||||

|Low/intermediate|384 (86.1)|202 (91.0)|177 (81.6)|

|High|62 (13.9)|20 (9.0)|40 (18.4)|

|High-risk stage III:|198 (43.8)|47 (26.3)|154 (70.6)|

|pT4|131 (29.0)|33 (14.6)|95 (43.6)|

|pN2|122 (27.0)|23 (10.2)|98 (44.9)|

|PANC (24), BTC (10), and other GI tumors (7) were treated with 50-200 mg BID LY3537982. Median| |---|

|age was 62 yrs (range, 36-85) and median number of prior lines of therapies was 3 (range, 0-11).|

|No DLTs were observed. Grade 1 diarrhea was the highest frequency TEAE regardless of at-|

|tribution (33%). At a median time on treatment of 4 months (range, 0.1-18), 20 pts are ongoing and|

|53 discontinued treatment. In the combination cohort, 46 pts with CRC were treated with 100 or|

|150 mg BID LY3537982 and cetuximab. Median age was 57 yrs (range, 35-77) and median number|

|of lines of prior therapies was 3 (range, 1-8). 1 pt at 100 mg BID had a DLT (ALT/AST increased)|

|and required a dose reduction. TEAEs $30% were dermatitis acneiform (59%), diarrhea (44%), dry|

|skin (44%), hypomagnesemia (33%), and fatigue (30%). Vomiting, pruritus, skin fissures,|

|headache, nausea, pyrexia, and rash were mostly grade 1 with 20-24% occurrence. At a median|

|time on treatment of 6 months (range, 0.6-11), 37 pts are ongoing and 9 discontinued treatment|

|(none due to AE).|

|Adverse events (AEs) occurred in 48 patients (94.1%), wherein grade 3-4 AEs occurred|

|in 23 (45.1%). No patients died due to AEs. Serious AEs occurred in 11 (21.6%) patients.|

|The most common AEs of any grade were rash (33.3%) and anemia (31.4%). Any-grade|

|and grade $3 treatment-related AEs (TRAEs) occurred in 36 (70.6%) and 13 (25.5%)|

|patients, respectively. Two patients achieved partial response and 18 had stable disease;|

|the objective response rate was 3.9% (90% confidence interval [CI], 0.7-11.8) and the|

|disease control rate was 39.2% (90% CI, 27.7-51.7). The median progression-free|

|survival and overall survival (OS) were 1.54 (90% CI, 1.41-2.79) and 10.68 months (90%|

|CI, 6.67-not reached [NR]), respectively. The proportion of patients continuing treatment|

|and OS in subgroups of different PD-L1 combined positive scores (CPS) showed a|

|tendency toward favorable efficacy in CPS-positive subgroups: the proportion of pa-|

|tients continuing treatment for 6 months was 4.5% (1/22) in those with CPS of 0 vs 20%|

|CRC|LY3537982 PANC BTC|Other GI d|LY3537982 + Cetuximab CRC|| |---|---|---|---|---|

|(N=32)|(N=24)|(N=10)|(N=7)|(N=46)|

||||||95|Poster Session| |---|---|---|---|---|---|---|

||||||Results: From July 2019 to October 2022, 106 eligible pts in total were enrolled.|Results: From July 2019 to October 2022, 106 eligible pts in total were enrolled.|

||||||According to the treatment received, 72 and 34 pts were respectively allocated into FP|According to the treatment received, 72 and 34 pts were respectively allocated into FP|

||||||cohort and TB cohort. With a global median follow-up of 14, the crude OS was 19.4 (95%|cohort and TB cohort. With a global median follow-up of 14, the crude OS was 19.4 (95%|

||||||CI: 17.9-NA) mo in FP cohort vs. 11.6 (10.0-17.2) mo in TB cohort. The HR of FP was|CI: 17.9-NA) mo in FP cohort vs. 11.6 (10.0-17.2) mo in TB cohort. The HR of FP was|

||||||0.384 (95% CI: 0.192-0.769, TB as reference). Multivariate Cox regression showed that|0.384 (95% CI: 0.192-0.769, TB as reference). Multivariate Cox regression showed that|

||||||the adjusted HR was 0.323 (95% CI: 0.149-0.704), which was adjusted with sex, age|the adjusted HR was 0.323 (95% CI: 0.149-0.704), which was adjusted with sex, age|

||||||greater than 65 yr, ECOG-PS, resection of primary lesion, radiotherapy history, location of|greater than 65 yr, ECOG-PS, resection of primary lesion, radiotherapy history, location of|

||||||lesion (left or right), metastases (liver, lung, and bone), and current line (3 or later). With|lesion (left or right), metastases (liver, lung, and bone), and current line (3 or later). With|

||||||PS, we performed three statistical methods, namely inverse probability weighting, PS|PS, we performed three statistical methods, namely inverse probability weighting, PS|

||||||matching (the sample size was 49 vs. 29 after matching), and additional adjustment for|matching (the sample size was 49 vs. 29 after matching), and additional adjustment for|

||||||PS with multivariate cox regression. The HRs of FP were 0.437 (95% CI: 0.200-0.953),|PS with multivariate cox regression. The HRs of FP were 0.437 (95% CI: 0.200-0.953),|

||||||0.446 (95% CI: 0.201-0.990), and 0.339 (95% CI: 0.153-0.748), respectively. Subgroup|0.446 (95% CI: 0.201-0.990), and 0.339 (95% CI: 0.153-0.748), respectively. Subgroup|

||||||analysis indicated that FP demonstrated lower HR in subgroup of male (0.296, 95% CI:|analysis indicated that FP demonstrated lower HR in subgroup of male (0.296, 95% CI:|

||||||0.117-0.753), right-sided lesion (0.177, 95% CI: 0.043-0.736), liver metastasis (0.291,|0.117-0.753), right-sided lesion (0.177, 95% CI: 0.043-0.736), liver metastasis (0.291,|

||||||95% CI: 0.112-0.756), and current line greater than 3 (0.303, 95% CI: 0.113-0.812).|95% CI: 0.112-0.756), and current line greater than 3 (0.303, 95% CI: 0.113-0.812).|

|Efficacy Evaluable a , n|32|24|10|6 e|38 f||

|ORR, n (%) PR, n (%)|4 (13) 4 (13) c|8 (33) 8 (33) c|5 (50) 5 (50)|3 (50) 3 (50) c|16 (42) 16 (42) g||

|SD, n (%)|23 (72)|14 (58)|3 (30)|3 (50)|20 (53)||

|PD, n (%) DCR b , n (%)|3 (9) 27 (84)|2 (8) 22 (92)|2 (20) 8 (80)|-6 (100)|1 (3) 36 (95)||

|96||||Poster Session|||

||||||:||

|66,1% (n=115) male, mean age at CRLM diagnosis 62,1 (611,5) years, 80,5% (n=140)|||||||

|with isolated liver metastases. Thirty-three pts (19%) had a second surgery, inde-|||||||

|pendently of the CERR score (chi-square p = 0,60). Eighteen (10,3%) pts had a CERR|||||||

|score of 0-1 (low-risk, LR), 96 (55,2%) of 2-3 (medium-risk, MR) and 60 (34,5%) of 4-5|||||||

|(high-risk, HiR). With a median (MED) follow-up of 85,1 (15,6-186,5) months (mo), 100|||||||

|(57.5%) pts have died. MED OS was 88,0 mo (95% confidence interval [CI] 40,6-135,4) for|||||||

|LR|||||||

||1L NIVO + IPI| |---|---|

|Efficacy|(N = 45)|

||||99|Poster Session| |---|---|---|---|---|

||||FOLFOXIRI 6 molecular targeting agent (bevacizumab or panitumumab) for|FOLFOXIRI 6 molecular targeting agent (bevacizumab or panitumumab) for|

||||conversion from unresectable to resectable in the advanced/recurrent co-|conversion from unresectable to resectable in the advanced/recurrent co-|

||||lorectal cancer. These regimens with powerful anti-tumor effects have enabled conversion from||

||||unresectable to resectable, giving patients a longer survival than those without con-|unresectable to resectable, giving patients a longer survival than those without con-|

||||version. Therefore, we explored the ideal regimen for conversion, focusing on FOLFOXIRI|version. Therefore, we explored the ideal regimen for conversion, focusing on FOLFOXIRI|

||||6 X. Methods: We retrospectively reviewed unresectable ARCC patients treated with|6 X. Methods: We retrospectively reviewed unresectable ARCC patients treated with|

||||FOLFOXIRI 6 X (X:Bmab, n=24; Pmab, n=1; alone, n=2; ) between February 2015 and|FOLFOXIRI 6 X (X:Bmab, n=24; Pmab, n=1; alone, n=2; ) between February 2015 and|

||||December 2022. The results were compared to those of patients who received other|December 2022. The results were compared to those of patients who received other|

||||regimens (OTHERS; n=212). Results: The median overall survival (OS) was 1072 days.|regimens (OTHERS; n=212). Results: The median overall survival (OS) was 1072 days.|

||||Forty-nine patients acquired conversion. The patients with conversion had a longer|Forty-nine patients acquired conversion. The patients with conversion had a longer|

||||progression-free survival and OS than those without conversion (p,0.0001|progression-free survival and OS than those without conversion (p,0.0001|

||||and ,0.0001, respectively). Conversion rates were 37.0% in FOLFOXIRI 6 X vs. 18.4% in|and ,0.0001, respectively). Conversion rates were 37.0% in FOLFOXIRI 6 X vs. 18.4% in|

||||OTHERS (p=0.0238), while response rates were 59.3% in FOLFOXIRI 6 X vs. 35.8% in|OTHERS (p=0.0238), while response rates were 59.3% in FOLFOXIRI 6 X vs. 35.8% in|

||||OTHERS (p=0.0185). The RAS wild-type group conversion rates were 30.0% in FOL-|OTHERS (p=0.0185). The RAS wild-type group conversion rates were 30.0% in FOL-|

||||FOXIRI 6 X vs. 20.6% in OTHERS, while 50.0% in FOLFOXIRI 6 X vs. 15.3% in OTHERS in|FOXIRI 6 X vs. 20.6% in OTHERS, while 50.0% in FOLFOXIRI 6 X vs. 15.3% in OTHERS in|

||||RAS mutant group. Anti-EGFR antibody +L-OHP-based doublet chemotherapy|RAS mutant group. Anti-EGFR antibody +L-OHP-based doublet chemotherapy|

||||accounted for conversion in 35.3% of the RAS wild-type group. Anti-VEGF antibody + L-|accounted for conversion in 35.3% of the RAS wild-type group. Anti-VEGF antibody + L-|

||||OHP based doublet chemotherapy attained 29.1% conversion rate in RAS mutant group.|OHP based doublet chemotherapy attained 29.1% conversion rate in RAS mutant group.|

|100||Poster Session|101|Poster Session|

|Results: As of July 10, 2023, 25 pts were treated (5, 11, 7, and 2 in Cohorts 1A, 1B, 1D, and 2B,|||||

|respectively). In Cohort 1A (TUC 150 mg PO BID), the most common TEAEs were diarrhea, fatigue,|||||

|nausea, and proteinuria (each in 60.0% [3/5]). For pts receiving TUC 300 mg PO BID, the most|||||

|common TEAEs were diarrhea (90.0% [18/20]) and fatigue (65.0% [13/20] ). Table 1 presents the|||||

|overall summary of adverse events. In Cohort 1A, Treatment-emergent adverse events (TEAEs)|||||

|leading to any treatment discontinuation were reported in 40.0% (2/5) pts, with 20.0% (1/5)|||||

|discontinuing tucatinib. For pts treated with TUC 300 mg, TEAEs leading to treatment discon-tinuation were reported in 35.0% (7/20), with 15.0% (3/20) discontinuing tucatinib. One TEAE leading to death (aspiration) in Cohort 1A was unrelated to study treatment. Grade $3 diarrhea was|were evaluable. All patients received FOLFOX in the past; two patients received 2 lines of||||

|observed in 45.5% (5/11) pts in Cohort 1B; most were observed in elderly pts or pts with gastric,|chemotherapies; one patient received 3 lines and eight patients had $ 4 lines before the|chemotherapies; one patient received 3 lines and eight patients had $ 4 lines before the|||

|gastroesophageal, or esophageal cancer or pts who were generally noncompliant with antidiarrheal|study. Five patients (41.7%) had disease resistance to FOLFOX. During the study, two|study. Five patients (41.7%) had disease resistance to FOLFOX. During the study, two|||

|treatment. No grade $3 diarrhea was observed in Cohort 1D. Among pts receiving TUC 300 mg, confirmed objective response rate was 83.3% (5/6) for mCRC, 40.0% (4/10) for gastroesophageal cancers, and 0% (0/4) for biliary tract cancer. Conclusions: TUC + Tras + FOLFOX showed manageable safety in the enrolled pt population and preliminary antitumor activity in pts with HER2+ mCRC and gastroesophageal cancer. This regimen will be compared with the standard of care (FOLFOX with or without bevacizumab/cetuximab) in the ongoing randomized, phase 3 study|patients received only 2 cycles of treatment due to poor PS. Two patients received 7 cycles, and nine patients completed 8 cycles of treatment. The common grade 3 & 4 AEs included neutropenia (46.2%), lymphopenia (30.8%), and abdominal pain (15.4%). No complete response was observed; two patients obtained partial response; nine patients had stable disease, and only one patient had progressive disease. The ORR was 16.7%,|patients received only 2 cycles of treatment due to poor PS. Two patients received 7 cycles, and nine patients completed 8 cycles of treatment. The common grade 3 & 4 AEs included neutropenia (46.2%), lymphopenia (30.8%), and abdominal pain (15.4%). No complete response was observed; two patients obtained partial response; nine patients had stable disease, and only one patient had progressive disease. The ORR was 16.7%,|||

|Safety summary.|||||

|Events, n (%)|TUC 150 mg (N=5)|TUC 300 mg (N=20)|||

|All TEAEs|5 (100)|20 (100)|||

|Treatment-related|4 (80.0)|20 (100)|||

|Grade ‡3 TEAEs|2 (40.0)|16 (80.0)|||

|Treatment-related|1 (20.0)|12 (60.0)|||

|Serious TEAEs|1 (20.0)|7 (35.0)|||

|Treatment-related|0|4 (20.0)|||

|||||||103|Poster Session| |---|---|---|---|---|---|---|---|

|||||||Methods: We conducted a non-intervention, prospective, observational study in pts|Methods: We conducted a non-intervention, prospective, observational study in pts|

|||||||with mCRC at 41 sites. The key eligibility criteria were ECOG performance status (PS) 0|with mCRC at 41 sites. The key eligibility criteria were ECOG performance status (PS) 0|

|||||||or 1, pts refractory to or intolerant of fluoropyrimidine, oxaliplatin, irinotecan, anti-|or 1, pts refractory to or intolerant of fluoropyrimidine, oxaliplatin, irinotecan, anti-|

|||||||angiogenesis, and anti-EGFR therapy if RAS status were wild type, and pts who plan to|angiogenesis, and anti-EGFR therapy if RAS status were wild type, and pts who plan to|

|||||||receive sequential treatment with REG and FTD/TPI BEV. Pts who starts with REG are|receive sequential treatment with REG and FTD/TPI BEV. Pts who starts with REG are|

|||||||enrolled in cohort A, FTD/TPI in cohort B, or FTD/TPI plus BEV in cohort C. The primary|enrolled in cohort A, FTD/TPI in cohort B, or FTD/TPI plus BEV in cohort C. The primary|

|||||||endpoint is overall survival (OS) of each group. Results: Between September 2020 and|endpoint is overall survival (OS) of each group. Results: Between September 2020 and|

|||||||December 2022, a total of 501 pts were enrolled and 455 were identified as full analysis|December 2022, a total of 501 pts were enrolled and 455 were identified as full analysis|

|||||||set. Pts' characteristics of cohort A (149 pts) / B (80 pts) /C (226 pts) were as follows:|set. Pts' characteristics of cohort A (149 pts) / B (80 pts) /C (226 pts) were as follows:|

|||||||median age 64.0 / 65.5 / 67.0 years, male 53.0 / 52.5 / 55.3%, ECOG PS 0 52.3 / 31.3 /|median age 64.0 / 65.5 / 67.0 years, male 53.0 / 52.5 / 55.3%, ECOG PS 0 52.3 / 31.3 /|

|||||||48.7%, tumor location right-sided 33.6 / 27.5 / 20.4%, RAS wild type 35.6 / 41.3 / 43.4%,|48.7%, tumor location right-sided 33.6 / 27.5 / 20.4%, RAS wild type 35.6 / 41.3 / 43.4%,|

|Overall survival (OS) was longer with FOLFIRI than iri (median 14.4 vs 9.8 months, p,0.001), as was TTNT (median 7.6 vs 5.3 months, p,0.001). In MVA, when controlling for age, comorbidities, CEA, ECOG performance status, and 1L, iri was associated with shorter OS than FOLFIRI (HR N Median OS (months; 95% CI) MVA HR (95% CI) Median TTNT (months; 95% CI) MVA HR (95% CI) 1.38, 95% CI 1.21-1.57, 2L|and BRAF V600E mutant type 6.7 / 7.5 / 4.0 %. Pts who received subsequent with FTD/ TPI BEV in cohort A / REG in cohort B / REG in cohort C were 62.4 / 37.5 / 62.8%. The median OS of cohort A / B / C was 11.8 / 7.1 / 10.2 months. Cox hazard model revealed hazard ratio (HR) 1.40 (95% confidence interval [CI] 1.01-1.94; p = 0.043) for cohort B, and HR 1.04 (95% CI 0.80-1.34; p = 0.784) for cohort C compared with cohort A. After|and BRAF V600E mutant type 6.7 / 7.5 / 4.0 %. Pts who received subsequent with FTD/ TPI BEV in cohort A / REG in cohort B / REG in cohort C were 62.4 / 37.5 / 62.8%. The median OS of cohort A / B / C was 11.8 / 7.1 / 10.2 months. Cox hazard model revealed hazard ratio (HR) 1.40 (95% confidence interval [CI] 1.01-1.94; p = 0.043) for cohort B, and HR 1.04 (95% CI 0.80-1.34; p = 0.784) for cohort C compared with cohort A. After||||||

|FOLFIRI|620|12.99 (11.18-15.16)|-|5.56 (5.10-6.08)|-|||

|FOLFIRI + anti-|1858 14.47 (13.51-15.65) 0.98 (0.87-1.09)|8.32 (7.76-8.78)|0.72 (0.66-0.79)|||||

|angiogenesis||||||||

|FOLFIRI + anti-EGFR|435|15.68 (13.61-18.51) 0.86 (0.74-0.99) 8.94 (7.86-10.03) 0.64 (0.56-0.72)||||||

|Iri|51|5.36 (3.81-8.09)|2.78 (2.03-3.80)|3.19 (2.66-4.70)|2.20 (1.65-2.94)|||

|Iri + anti-angiogenesis|82|11.31 (8.71-18.38)|1.29 (0.99-1.67)|5.33 (4.67-7.92)|1.00 (0.79-1.26)|||

|Iri + anti-EGFR|169|11.44 (8.78-13.45)|1.16 (0.95-1.40)|6.48 (5.52-7.17)|0.96 (0.81-1.14)|||

|104||||Poster Session||||

||||||Part A|||

|between Sept 2022-April 2023. As of 21 Aug 2023, median age 56 years (35, 84); 20||||||||

|males. 29 pts had tumors with evaluable baseline DKK1 expression; 55% were DKK1-||||||||

|expressing ($1% tumor cells). All patients had received prior 5FU-based therapies, 30||||||||

|pts (91%) with oxaliplatin in combination and 17 pts (52%) had prior bevacizumab. 24 pts||||||||

|(73%) had RAS mutations (22 KRAS, 2 NRAS) and 23 pts (70%) had liver metastasis. 30||||||||

|pts (91%) received DKN-01 + bevacizumab + FOLFIRI. 17 pts (52%) had $grade 3||||||||

|treatment related adverse events (TRAE) with neutrophil count decreased, anemia and||||||||

|fatigue representing the most common. No pt discontinued DKN-01 due to a TRAE. Of||||||||

|the 27 response evaluable pts the ORR was 30% and the DCR was 93%: 8 PR, 17 SD and 2||||||||

|4%), KRAS| |---|

|G12V in 72 (21.2%), KRAS G13D in 43 (12.6%) and KRAS G12C in 16 (4.7%). There were|

|80 patients in the G12D group and 260 in the non-G12D group. Patient backgrounds did|

|not differ significantly in terms of age (median 61/63), sex (male 49%/48%), performance|

|status (PS0 32%/32%), site of primary tumor (right 33%/32%), number of metastatic|

|sites (3# 28%/23%), treatment regimen (doublet 90%/92%, triplet 3%/4%), or first line|

|bevacizumab (yes 81%/79%). Median PFS was 9.2 months (95%CI: 7.8-12.2) in the G12D|

|group vs. 11.5 months (95%CI: 9.2-13.1) in the non-G12D group (HR 0.97 [95%CI: 0.73-|

|1.28]; p=0.81). Median OS was 25.8 months (95%CI: 18.8-39.8) vs 32.9 months (95%CI:|

|28.5-36.1) (HR 0.84 [95%CI: 0.60-1.19]; p=0.33). Second-line treatment was adminis-|

|tered in 55 (69%) vs 192 (74%) patients in the G12D and non-G12D group, respectively.|

|Conversion surgery was performed in 4 (5%) vs 18 (7%) patients in the G12D and non-|

||||107|||||Poster Session|| |---|---|---|---|---|---|---|---|---|---|

|combination of FOLFIRI and anti-angiogenesis inhibitors (AAIs) or anti-epidermal growth||||||||||

|factor receptor (EGFR) monoclonal antibodies (mAbs) after adjuvant FOLFOX or CAPOX||||||||||

|therapy. The study included patients with CRC who underwent surgical resection, started||||||||||

|adjuvant chemotherapy #3 months (mo) after the first surgery, had early recurrence of CRC||||||||||

|(defined as initiation of FOLFIRI + AAIs/anti-EGFR mAbs second line [2L] regimen) within 1 year after adjuvant chemotherapy ended. Patient characteristics at baseline of 2L (60 days prior to 2L initiation) and treatment sequence were summarized descriptively; time to discontinuation (TTD) for adjuvant and 2L therapy were analyzed using Kaplan-Meier method. Cox proportional hazard model was used to identify risk factors associated with|Data used to create the nomogram. HR Performance status 0|Univariate 95%CI (Reference)|P ,0.0001|HR|Multivariate 95%CI (Reference)|P ,0.0001||||

|TTD of 2L regimen. Results: The cohort included 832 patients: median (range) age was 67|1 Gender|1.48|1.24-1.75|0.3502|1.57|1.31-1.89||||

|(24-86) years, 56.4% males, 65.5% with left-sided CRC. Most patients received CAPOX (71.3%) as adjuvant therapy. Median (95% CI) duration of adjuvant therapy was 5.4 mo (5.3-|Female Male Age at enrollment|0.92 1.01|(Reference) 0.78-1.09 1.00-1.02|0.0328|1.00|1.00-1.01|0.3979|||

|5.5). As 2L therapy, 72.5% and 27.5% of patients received FOLFIRI + AAIs (AAIs group) and FOLFIRI + anti-EGFR mAbs (anti-EGFR group), respectively.|BMI Albumin (g/L) LDH (U/L) N of Metastatic Sites|0.98 0.99 1.00|0.96-1.00 0.98-0.99 1.00-1.00|0.0156 0.0071 0.0039 ,0.0001|0.99|0.97-1.01|0.3188|||

||||1||(Reference)|||||

||||2+|1.77|1.39-2.25|||||

||||Royal Marsden Hospital score|||,0.0001|||0.0028|

||||0-1|0-1|0-1|0-1||(Reference)||

||||2-3|2-3|2-3|2-3|1.84|1.50-2.26||

|Median Age, yrs (Range)||59(51-85)|Primary Site Location Colon||(Reference)|0.0140||(Reference)|0.0217|

|ECOG PS, % Prior systemic regimens, %|0 1 2 2|4(40) 4(40) 2(20) 2(20)|Rectum Liver metastases No Yes Lung metastases No|0.80 1.78|0.67-0.96 (Reference) 1.48-2.15 (Reference)|,0.0001 0.3890|0.80 1.66|0.67-0.97 (Reference) 1.36-2.02|,0.0001|

|Median PFS, wks (95% CI) Median OS, wks (95% CI)||8(6, 8) 24(7, 43)|Stage at diagnosis I-III IV|1.17|(Reference) 0.92-1.47|0.1946||||

|108||Poster Session|109|||||Poster Session||

|Results: The numbers of proximal, mid, and distal TCC were 48 (45.3%), 32 (30.2%), and 26 (24.5%), respectively. The numbers of right hemicolectomy, transverse colectomy and left hemicolectomy were 57 (53.8%), 28 (26.4%) and 21 (19.8%). The numbers of No CVL group and CVL group were 47 (44.3%) and 59 (55.7%). The numbers of stage I, II and III were 24 (22.6%), 45 (42.5%), 37 (34.9%), and 49 patients underwent adjuvant treatment. The most frequent organ of recurrence was peritoneum (N=6, 5.6%). There was no|was 29% (95% CI 15-47): two complete responses (CR; 6%), eight PR (24%), 17 stable disease (SD; 50%), two PD (6%), and five not evaluable (15%). Median time to response was 1.8 months (mo). Median duration of response (DoR), progression-free survival (PFS), and overall survival (OS) were 27.3 mo (95% CI 5.6-not estimable [NE]), 7.2 mo (95% CI 3.5-12.3), and 14.1 mo (95% CI 6.1-36.5). In the 19 IRC-eligible pts with CRC, ORR was 47% (95% CI 24-71): two CR (11%), seven PR (37%), nine SD (47%), and one not evaluable (5%); five of nine responders were MSI-H. Median DoR, PFS, and OS for all IRC-eligible pts with CRC were 27.3 mo (95% CI 5.6-NE), 29.4 mo (95% CI|||||||||

|statistically significant difference of stage, mean number of retrieved lymph node (24.12|5.4-NE), and 29.4 mo (95% CI 6.1-NE). Treatment duration ranged from 0.3 to 44+ mo. At|||||||||

|||111|Poster Session| |---|---|---|---|

|||Efficacy and safety of trifluridine/tipiracil in combination with bevacizumab|Efficacy and safety of trifluridine/tipiracil in combination with bevacizumab|

|||in older and younger patients with refractory metastatic colorectal cancer: A|in older and younger patients with refractory metastatic colorectal cancer: A|

|||subgroup analysis of the phase 3 SUNLIGHT trial. First Author: Julien Taieb,|subgroup analysis of the phase 3 SUNLIGHT trial. First Author: Julien Taieb,|

|||Université Paris-Cité, (Paris Descartes), Georges Pompidou European Hospital, SIRIC|Université Paris-Cité, (Paris Descartes), Georges Pompidou European Hospital, SIRIC|

|||CARPEM, Paris, France||

|||Background: SUNLIGHT, an international, open-label, randomized, phase 3 study|Background: SUNLIGHT, an international, open-label, randomized, phase 3 study|

|||comparing trifluridine/tipiracil (FTD/TPI) + bevacizumab (FTD/TPI + bev) to FTD/TPI|comparing trifluridine/tipiracil (FTD/TPI) + bevacizumab (FTD/TPI + bev) to FTD/TPI|

|||monotherapy in patients with refractory metastatic colorectal cancer (mCRC),|monotherapy in patients with refractory metastatic colorectal cancer (mCRC),|

|||demonstrated a 3.3-month increase in overall survival from 7.5 months with FTD/TPI|demonstrated a 3.3-month increase in overall survival from 7.5 months with FTD/TPI|

|||monotherapy to 10.8 months with FTD/TPI + bev (HR, 0.61; 95% CI: 0.49-0.77;|monotherapy to 10.8 months with FTD/TPI + bev (HR, 0.61; 95% CI: 0.49-0.77;|

|||P,0.001). This subgroup analysis of SUNLIGHT examined efficacy and safety outcomes|P,0.001). This subgroup analysis of SUNLIGHT examined efficacy and safety outcomes|

|||by age. Methods: In SUNLIGHT, patients with mCRC with ECOG PS of 0-1 and two prior|by age. Methods: In SUNLIGHT, patients with mCRC with ECOG PS of 0-1 and two prior|

|||treatment regimens were randomized to receive FTD/TPI + bev or FTD/TPI. A subgroup|treatment regimens were randomized to receive FTD/TPI + bev or FTD/TPI. A subgroup|

|||analysis was performed to evaluate efficacy and safety outcomes in patients aged ,65,|analysis was performed to evaluate efficacy and safety outcomes in patients aged ,65,|

|||65-74, and $75 years. Results: Among 492 randomized patients (n=246 FTD/TPI + bev;|65-74, and $75 years. Results: Among 492 randomized patients (n=246 FTD/TPI + bev;|

|||n=246 FTD/TPI), 56%, 32%, and 12% were aged ,65, 65-74, and $75 years, respectively.|n=246 FTD/TPI), 56%, 32%, and 12% were aged ,65, 65-74, and $75 years, respectively.|

|||Concerning overall survival, hazard ratios for FTD/TPI + bev vs FTD/TPI monotherapy|Concerning overall survival, hazard ratios for FTD/TPI + bev vs FTD/TPI monotherapy|

|||were 0.65 (95% CI: 0.48-0.87), 0.64 (95% CI: 0.43-0.94), and 0.49 (95% CI: 0.27-0.90) in|were 0.65 (95% CI: 0.48-0.87), 0.64 (95% CI: 0.43-0.94), and 0.49 (95% CI: 0.27-0.90) in|

|||patients aged ,65, 65-74, and $75 years, respectively. Regardless of age, patients|patients aged ,65, 65-74, and $75 years, respectively. Regardless of age, patients|

|||receiving FTD/TPI + bev experienced improved progression-free survival and improved|receiving FTD/TPI + bev experienced improved progression-free survival and improved|

|||time to worsening of ECOG PS to $2. Among FTD/TPI + bev treated patients, frequency|time to worsening of ECOG PS to $2. Among FTD/TPI + bev treated patients, frequency|

|||of any-cause severe adverse events (AEs) was slightly higher in the 65-74 subgroup [69%|of any-cause severe adverse events (AEs) was slightly higher in the 65-74 subgroup [69%|

|||(,65); 80% (65-74); 67% ($75 years)]. Frequency of grade 3 and 4 neutropenia was also|(,65); 80% (65-74); 67% ($75 years)]. Frequency of grade 3 and 4 neutropenia was also|

|||slightly higher in the 65-74 subgroup [38% (,65); 54% (65-74); 42% ($75 years)]. AE-|slightly higher in the 65-74 subgroup [38% (,65); 54% (65-74); 42% ($75 years)]. AE-|

|||related discontinuation rates were similar across age subgroups [11.6% (,65 years),|related discontinuation rates were similar across age subgroups [11.6% (,65 years),|

|||13.2% (65-74), and 16.7% ($75 years)]. Conclusions: The results of this subgroup|13.2% (65-74), and 16.7% ($75 years)]. Conclusions: The results of this subgroup|

|||analysis demonstrate the efficacy benefit and tolerability of FTD/TPI + bevacizumab|analysis demonstrate the efficacy benefit and tolerability of FTD/TPI + bevacizumab|

|||treatment regardless of age in refractory mCRC patients. Clinical trial information:|treatment regardless of age in refractory mCRC patients. Clinical trial information:|

|||NCT04737187. Research Sponsor: Institut de Recherches Internationales Servier; Taiho|NCT04737187. Research Sponsor: Institut de Recherches Internationales Servier; Taiho|

|||Oncology.||

|112|Poster Session|113|Poster Session|

||for|||

|LMs, and safety. Results: As of September 14, 2023, 45 patients were enrolled in cohort|Results: Forty-three patients were enrolled between November 2019 and October 2022,|Results: Forty-three patients were enrolled between November 2019 and October 2022,||

|A, the median age was 67 years (35-75), 66.7% male, 91.1% ECOG-PS 1 and 60% had LMs|and 43 were analyzed (median age 68 years (range 27-80); male, 69.8%; ECOG PS 0/1,|and 43 were analyzed (median age 68 years (range 27-80); male, 69.8%; ECOG PS 0/1,||

|only. After induction therapy, 8 patients received surgical resection. Currently, 13|72.1%/27.9%; left sided primary tumor, 90.7%). The primary endpoint was met: 6-month|72.1%/27.9%; left sided primary tumor, 90.7%). The primary endpoint was met: 6-month||

|patients are receiving induction therapy and 10 are undergoing maintenance therapy,|PFS rate was 58.7% (90%CI, 45.5%-71.9%). Median PFS and OS were 7.3 months (95%CI,|PFS rate was 58.7% (90%CI, 45.5%-71.9%). Median PFS and OS were 7.3 months (95%CI,||

|with a maximum duration of treatment (DOT) of 13.7 months. Of 39 evaluable patients in|5.5-11.0 months) and 18.8 months (95%CI, 12.9-26.6 months), respectively. The ORR|5.5-11.0 months) and 18.8 months (95%CI, 12.9-26.6 months), respectively. The ORR||

|cohort A, ORR and DCR were 48.7% and 97.4% (PR, n=19; SD, n=19, 16 SD had reduced|was 23.3 % (95%CI, 11.8-38.6%) and DCR was 88.4% (95%CI, 74.9-96.1%). Mean RDI of|was 23.3 % (95%CI, 11.8-38.6%) and DCR was 88.4% (95%CI, 74.9-96.1%). Mean RDI of||

|tumor size). The median PFS was not reached. 36 patients had TEAEs and $ grade 3|AFL, irinotecan, bolus 5-FU and infusional 5-FU were 75.3% (SD, 26.2), 50.6% (SD, 12.5),|AFL, irinotecan, bolus 5-FU and infusional 5-FU were 75.3% (SD, 26.2), 50.6% (SD, 12.5),||

|TEAEs (33.3%) mainly included neutropenia (11.1%), hypertension (6.7%), and white|31.6% (SD, 26.6), and 58.7% (SD, 7.21), respectively. The main grade $3 adverse events|31.6% (SD, 26.6), and 58.7% (SD, 7.21), respectively. The main grade $3 adverse events||

|||included hypertension (62.||

|115|||||||Poster Session||| |---|---|---|---|---|---|---|---|---|---|

|Prognostic factors of patients (pts) with salvage-line metastatic colorectal||||||||||

|cancer (mCRC). Results: The adjusted hazard ratios (HRs) (95% confidence interval [CI]) were 0.52 (0.40-0.67)||||||||||

|for the number of metastatic sites (1 vs 2+), 0.71 (0.59-0.84) for ECOG performance status (PS) (0 vs 1), 0.54||||||||||

|(0.45-0.66) for liver metastases (No vs Yes), 0.54 (0.40-0.71) for peritoneal metastases (No vs Yes), and 0.51||||||||||

|(0.38-0.70) for Royal Marsden Hospital (RMH) Score (consisting of albumin level, number of metastatic sites,||||||||||

|and LDH level) (0-1 vs 2-3). Conclusions: OS||||PFS||||||

|||||||Median||||

|||Median (months) 95% CI Adjusted HR 95% CI|(months) 95% CI Adjusted HR 95% CI|||||||

|N of metastatic sites|1|8.1|7.2, 10.8|0.52|0.40, 0.67|1.8|1.7, 1.8|0.85|0.68, 1.05|

||(n=106)|||||||||

||2+|5.1|4.6, 5.6|-|-|1.7|1.7, 1.8|-|-|

||(n=559)|||||||||

|ECOG PS|0|6.7|5.6, 7.3|0.71|0.59, 0.84|1.8|1.7, 1.8|0.87|0.75, 1.02|

||(n=337)|||||||||

||1|4.9|4.2, 5.6|-|-|1.7|1.7, 1.8|-|-|

||(n=386)|||||||||

|Liver metastases|No|7.4|7.1, 8.2|0.54|0.45, 0.66|1.8|1.7, 1.8|0.66|0.56, 0.78|

||(n=257)|||||||||

||Yes|4.5|4.1, 4.9|-|-|1.7|1.7, 1.7|-|-|

||(n=401)|||||||||

|Peritoneal metastases|No|5.8|5.3, 6.4|0.54|0.40, 0.71|1.7|1.7, 1.8|0.75|0.58, 0.97|

||(n=591)|||||||||

||Yes|3.2|2.4, 4.6|-|-|1.6|1.2, 1.7|-|-|

||(n=67)|||||||||

|RMH score|0-1|7.6|6.6, 11.0|0.51|0.38, 0.70|1.8|1.7, 1.8|0.73|0.57, 0.93|

||(n=98)|||||||||

||2-3|4.5|3.8, 5.1|-|-|1.7|1.6, 1.8|-|-|

||(n=246)|||||||||

|Previous treatments|Prev Trt 1|7.3|5.9, 8.9|0.67|0.51, 0.89|1.7|1.7, 1.8|0.92|0.71, 1.19|

||(n=92)|||||||||

||Prev Trt 2|7.1|6.0, 11.1|0.51|0.35, 0.74|1.7|1.6, 1.8|0.90|0.64, 1.26|

||(n=42)|||||||||

||Prev Trt 3|5.0|4.4, 5.8|0.94|0.78, 1.14|1.7|1.7, 1.8|1.12|0.95, 1.33|

||(n=336)|||||||||

||Prev Trt 4|5.4|4.8, 6.0|-|-|1.7|1.7, 1.8|-|-|

||(n=253)|||||||||

|119|Poster Session| |---|---|

|Methods: Pts with histologically confirmed mCRC who achieved disease control (in-|Methods: Pts with histologically confirmed mCRC who achieved disease control (in-|

|cluding CR/PR and SD) after at least six cycles of first-line standard chemotherapy were|cluding CR/PR and SD) after at least six cycles of first-line standard chemotherapy were|

|included in the study. During phase Ib, pts received Fru (4 mg p.o. qd, 3 weeks on/1 week|included in the study. During phase Ib, pts received Fru (4 mg p.o. qd, 3 weeks on/1 week|

|off, q4w]) plus Cap (850 mg/m 2 , p.o. bid, d1-7 and d15-21, q4w). In phase II, pts were|off, q4w]) plus Cap (850 mg/m 2 , p.o. bid, d1-7 and d15-21, q4w). In phase II, pts were|

|randomized in a 1:1 ratio to receive either Fru (RP2D, 3mg, 3 weeks on/1 week off) plus|randomized in a 1:1 ratio to receive either Fru (RP2D, 3mg, 3 weeks on/1 week off) plus|

|Cap or Cap alone. The primary outcome was progression-free survival (PFS).|Cap or Cap alone. The primary outcome was progression-free survival (PFS).|

|Results: By Sep 10, 2023, a total of 34 pts were enrolled in the study, and 26 pts were|Results: By Sep 10, 2023, a total of 34 pts were enrolled in the study, and 26 pts were|

|considered evaluable for efficacy. During Fru plus Cap (n=14) and Cap (n=12), the|considered evaluable for efficacy. During Fru plus Cap (n=14) and Cap (n=12), the|

|median age was 61.5 (39-78) and 57.5 (32-75) years. The main primary tumor side was|median age was 61.5 (39-78) and 57.5 (32-75) years. The main primary tumor side was|

|left (64.3% / 66.7%) and approximately half of the pts harbored a RAS mutation (50.0% /|left (64.3% / 66.7%) and approximately half of the pts harbored a RAS mutation (50.0% /|

|58.3%). Most pts had previously received bevacizumab therapy (57.1% /58.3%) or|58.3%). Most pts had previously received bevacizumab therapy (57.1% /58.3%) or|

|cetuximab (35.7% /25.0%), respectively. The mPFS was significantly improved in Fru|cetuximab (35.7% /25.0%), respectively. The mPFS was significantly improved in Fru|

|plus Cap vs Cap (9.1 vs 3.8 months, HR: 0.289, 95% CI 0.083 to 1.01, p=0.039).|plus Cap vs Cap (9.1 vs 3.8 months, HR: 0.289, 95% CI 0.083 to 1.01, p=0.039).|

|Consistently, ORR (21.4% vs 0%) and DCR (92.9% vs 66.7%) were improved with Fru plus|Consistently, ORR (21.4% vs 0%) and DCR (92.9% vs 66.7%) were improved with Fru plus|

|Cap. Grades 3 and 4 treatment-emergent adverse events (TEAEs) were hypertension|Cap. Grades 3 and 4 treatment-emergent adverse events (TEAEs) were hypertension|

|(11.1%), oral mucositis (5.6%), voice alteration (5.6%), small intestinal obstruction|(11.1%), oral mucositis (5.6%), voice alteration (5.6%), small intestinal obstruction|

|(5.6%), acrodynia (5.6%) and blood bilirubin increased (5.6%) in Fru plus Cap, and|(5.6%), acrodynia (5.6%) and blood bilirubin increased (5.6%) in Fru plus Cap, and|

|diarrhea (6.3%), oral mucositis (6.3%) and acrodynia (6.3%) in Cap therapy.|diarrhea (6.3%), oral mucositis (6.3%) and acrodynia (6.3%) in Cap therapy.|

|||||121||||||Poster Session|Poster Session|Poster Session| |---|---|---|---|---|---|---|---|---|---|---|---|---|

|||||Summary of 5 patients with dMMR rectal cancer receiving short course nivo-ipi.|Summary of 5 patients with dMMR rectal cancer receiving short course nivo-ipi.|Summary of 5 patients with dMMR rectal cancer receiving short course nivo-ipi.|Summary of 5 patients with dMMR rectal cancer receiving short course nivo-ipi.|Summary of 5 patients with dMMR rectal cancer receiving short course nivo-ipi.|Summary of 5 patients with dMMR rectal cancer receiving short course nivo-ipi.|Summary of 5 patients with dMMR rectal cancer receiving short course nivo-ipi.|Summary of 5 patients with dMMR rectal cancer receiving short course nivo-ipi.|Summary of 5 patients with dMMR rectal cancer receiving short course nivo-ipi.|

||||||Age|||No of|Clinical|Response||Follow-up|

|||||Pt.no|(years)|dMMR IHC status|Stage|nivo-ipi|relief (days)|(months)|ctDNA|(months)|

|Patient characteristics.||||1|39|MSH2 and MSH6 absent T3N1|1|, 15|rCR at 5 cCR at 1|Pos ⇨ neg|42||

||Combination (N, %)||2|35|MSH2 and MSH6 absent|T3N2|2|, 15|pCR at 1 cCR at 4|Pos ⇨ neg|17||

|Variables|Anti-VEGF|Anti-EGFR|p|||Lynch syndrome||||rCR at 11 pCR at 2|||

|Total number Age > 65 Male|10 (100) 3 (30.0) 7 (70.0)|20 (100) 9 (45.0) 10 (50.0)|0.694 0.440|3 4|83 86|MLH1 and PMS2 Absent MSH6 absent|T4N0 T3N1|1 1|, 15 , 15|cCR at 1 rCR at 4 pCR at 1 cCR at 1|Pos ⇨ neg Pos ⇨ neg|8 2|

|Left-sided tumor Synchronous metastatic disease Combined other chemotherapies|9 (90.0) 5 (50.0) 6 (60.0)|17 (85.0) 15 (75.0) 14 (70.0)|1.000 1.000 0.396|5|53|absent MLH1 and PMS2|T2N2|1|, 15|rCR: too early pCR at 1 pCR: too early rCR: too early cCR at 1|Too early|1|

|Treatment line, median (range)|5 (3-7)|5 (4-11)|||||||||||

|127|Poster Session| |---|---|

|Results of a phase 1b/2 study of ADG126 (a masked anti-CTLA-4 SAFEbody)|Results of a phase 1b/2 study of ADG126 (a masked anti-CTLA-4 SAFEbody)|

|in combo with pembrolizumab (Pembro) in patients (Pts) with metastatic|in combo with pembrolizumab (Pembro) in patients (Pts) with metastatic|

|microsatellite-stable (dependent cellular cytotoxicity (ADCC)/phagocytosis (ADPC). Preclinical studies showed||

|that ADG126/Pembro combination effectively increases T eff /T reg ratio. In Phase 1b/2|that ADG126/Pembro combination effectively increases T eff /T reg ratio. In Phase 1b/2|

|studies, ADG126 demonstrated a favorable safety profile and clinical efficacy as mono-|studies, ADG126 demonstrated a favorable safety profile and clinical efficacy as mono-|

|therapy and in combination with anti-PD-1 therapy. Here we present results of the entire dose escalation and ongoing dose expansion cohorts including a cohort of patients with MSS CRC free of liver metastasis (NCT05405595). Methods: This is a Phase 1b/2, open-label, multicenter dose escalation and expansion study of ADG126/Pembro. Pts received ADG126 [6 or 10 mg/kg (mpk), Q3W or Q6W, IV] plus Pembro (200 mg, Q3W, IV). Primary endpoints are safety and tolerability. Secondary endpoints are PK, ADA, ORR, DCR, DOR and PFS per RECIST 1.1. Results: As of Aug 29, 2023, a total of 47 Pts have been treated in dose escalation (N=11) and expansion cohorts (N=36). The median age is 60.5 yrs (26-78); 31.9% Pts had at least 3 prior therapies, 12.8% Pts received prior IO therapies. A majority of Pts (74.5%) have what are considered immunologically "cold" tumors. ADG126 was dosed at 6 mpk Q6W (1 Pt) and Q3W (5 Pts), 10 mpk Q6W (17 Pts) and Q3W (24 Pts), and Pembro was dosed at 200 mg Q3W. No DLT or Grade 4/5 TRAE was observed at any dose level. TRAEs more than 10% are pruritis (N=9, 19.1%) and diarrhea (N=5, 10.6%). Grade 3 TRAEs were observed in 5 subjects: 1 G3 diarrhea (6 mpk, 16.7%), 1 G3 adrenal insufficiency (10 mpk Q6W, 5.128 According to the protocol, 110 patients would be randomly assigned (2:1) to fruquintinib (FR) group (4mg once daily for 21 days, followed by 7 days off in 28 day cycles) or observation (OB) group via interactive web response system. The primary endpoint was progression-free survival (PFS). Results: Up to Aug 22, 2023, 28 and 14 patients had been enrolled in FR group and OB group, of whom the median age was 61 (44 to 73) vs. 66.5 (36 to 81), including 20 (71%) vs. 10 (71%) males, respectively. 26 (93%) vs. 11 (79%) patients were RAS-mutant. In the full analysis set (FAS), the median PFS were 5.26 (95% CI: 3.71-19.12) months and 2.99 (95% CI: 1.91-4.63) months (HR=0.36; p=0.0158). 25 and 13 pts from two groups received at least one response evaluation after baseline, respectively. The disease control rate (DCR) was 88.00% (22/25) vs. 53.85% (7/13) (OR=6.29, 95% CI: 1.31-36.7; p=0.0267). As to the per-protocol set (PPS), since 6 pts in FR group initiated with a lower dose (3mg), the number of patients was 22 vs. 14. The median PFS were 6.51 (95% CI: 3.88-19.12) months and 2.99 (95% CI: 1.91-4.63) months (HR=0.25; p=0.0061). The DCR was 89.47% (17/19) vs. 53.85% (7/13) Poster Session|therapy and in combination with anti-PD-1 therapy. Here we present results of the entire dose escalation and ongoing dose expansion cohorts including a cohort of patients with MSS CRC free of liver metastasis (NCT05405595). Methods: This is a Phase 1b/2, open-label, multicenter dose escalation and expansion study of ADG126/Pembro. Pts received ADG126 [6 or 10 mg/kg (mpk), Q3W or Q6W, IV] plus Pembro (200 mg, Q3W, IV). Primary endpoints are safety and tolerability. Secondary endpoints are PK, ADA, ORR, DCR, DOR and PFS per RECIST 1.1. Results: As of Aug 29, 2023, a total of 47 Pts have been treated in dose escalation (N=11) and expansion cohorts (N=36). The median age is 60.5 yrs (26-78); 31.9% Pts had at least 3 prior therapies, 12.8% Pts received prior IO therapies. A majority of Pts (74.5%) have what are considered immunologically "cold" tumors. ADG126 was dosed at 6 mpk Q6W (1 Pt) and Q3W (5 Pts), 10 mpk Q6W (17 Pts) and Q3W (24 Pts), and Pembro was dosed at 200 mg Q3W. No DLT or Grade 4/5 TRAE was observed at any dose level. TRAEs more than 10% are pruritis (N=9, 19.1%) and diarrhea (N=5, 10.6%). Grade 3 TRAEs were observed in 5 subjects: 1 G3 diarrhea (6 mpk, 16.7%), 1 G3 adrenal insufficiency (10 mpk Q6W, 5.128 According to the protocol, 110 patients would be randomly assigned (2:1) to fruquintinib (FR) group (4mg once daily for 21 days, followed by 7 days off in 28 day cycles) or observation (OB) group via interactive web response system. The primary endpoint was progression-free survival (PFS). Results: Up to Aug 22, 2023, 28 and 14 patients had been enrolled in FR group and OB group, of whom the median age was 61 (44 to 73) vs. 66.5 (36 to 81), including 20 (71%) vs. 10 (71%) males, respectively. 26 (93%) vs. 11 (79%) patients were RAS-mutant. In the full analysis set (FAS), the median PFS were 5.26 (95% CI: 3.71-19.12) months and 2.99 (95% CI: 1.91-4.63) months (HR=0.36; p=0.0158). 25 and 13 pts from two groups received at least one response evaluation after baseline, respectively. The disease control rate (DCR) was 88.00% (22/25) vs. 53.85% (7/13) (OR=6.29, 95% CI: 1.31-36.7; p=0.0267). As to the per-protocol set (PPS), since 6 pts in FR group initiated with a lower dose (3mg), the number of patients was 22 vs. 14. The median PFS were 6.51 (95% CI: 3.88-19.12) months and 2.99 (95% CI: 1.91-4.63) months (HR=0.25; p=0.0061). The DCR was 89.47% (17/19) vs. 53.85% (7/13) Poster Session|

|23, 2023, this||

|cohort was fully enrolled; all 20 patients (50% female, median age 60.0 years) were||

|included in this analysis. All patients received fluoropyrimidine-based treatment and 17||

|(85%) patients received oxaliplatin-based treatment as first-line therapy. Any-grade||

|treatment-related adverse events (TRAEs) occurred in 19 (95%) patients. The most||

|common any-grade TRAEs were dermatitis acneiform (60%), dry skin (55%), pruritus||

|(45%), and hypomagnesemia (30%). Grade $3 TRAEs occurred in 4 (20%) patients and||

|included fatigue, hypomagnesemia, decreased appetite, and rash (5% each). No TRAEs||

|were grade $4 or resulted in treatment discontinuation or deaths. Confirmed ORR was||

|30% (95% CI: 11.9, 54.3). The disease control rate was 90% (95% CI: 68.3, 98.8). At a||

|median follow-up of 11.3 months (95% CI: 5.6, not estimable), median PFS was||

|8.3 months (95% CI: 4.3, 14.1). Conclusions: This is the first report of safety and efficacy from a 2L cohort evaluating a KRAS G12C inhibitor plus an anti-EGFR antibody in||

|KRAS G12C-mutated metastatic colorectal cancer. The toxicities of sotorasib plus||

|Poster Session| |---|

|||||131|Poster Session| |---|---|---|---|---|---|

|||||May 29, 2023. Methods: RAS/BRAF wild-type unresectable mCRC patients with no prior|May 29, 2023. Methods: RAS/BRAF wild-type unresectable mCRC patients with no prior|

|||||systemic treatment received anlotinib (12 mg p.o. qd, d1-d14, q3w), capecitabine (850 mg/m 2 p.o., bid, d1-d14, q3w) and oxaliplatin (130 mg/m 2 i.v., d1, q3w) for 6 cycles|systemic treatment received anlotinib (12 mg p.o. qd, d1-d14, q3w), capecitabine (850 mg/m 2 p.o., bid, d1-d14, q3w) and oxaliplatin (130 mg/m 2 i.v., d1, q3w) for 6 cycles|

|||||followed by anlotinib and capecitabine as maintenance therapy until disease pro-|followed by anlotinib and capecitabine as maintenance therapy until disease pro-|

|||||gression. Tumor response was assessed every 6 weeks according to RECIST v1.1 by|gression. Tumor response was assessed every 6 weeks according to RECIST v1.1 by|

|||||investigator. The primary endpoint was ORR, and secondary endpoints included safety,|investigator. The primary endpoint was ORR, and secondary endpoints included safety,|

|||||DCR, DOR and PFS. Results: From Nov 2019 to February 2021, 30 eligible patients were|DCR, DOR and PFS. Results: From Nov 2019 to February 2021, 30 eligible patients were|

|||||enrolled, of whom, median age was 60y (range, 32-72y), 26 (86.7%) had left colon or|enrolled, of whom, median age was 60y (range, 32-72y), 26 (86.7%) had left colon or|

|24 (0.12-0.46) compared to 0.52 (0.28-0.96) and OS HR of 0.75 (0.42-1.34) compared to 1.17 (0.66-2.08), demonstrating potential predictive value. Median PFS in months (95% CI) CAP-B Observation|rectal cancer, and 25 (83.3%) had liver metastases. In previous reports, ORR, DCR, and median PFS were 76.7%, 93.3%, and 11.3 months, respectively. At a Median follow-up of 31.7 months (95% CI, 27.8-35.6), the median OS was 29.7 months (95% CI, 21.2-38.2), the 24-month OS rate was 55.0% (95%CI, 35.4-70.9%) and the 30-month OS rate was 40.6% (95%CI:21.6-58.9%). Conclusions: Anlotinib combined with oxaliplatin and capecitabine achieved considerable OS and showed potential efficacy as first-line therapy for mCRC with manageable toxicity profiles. Clinical trial information: NCT04080843. Research Sponsor: None.|rectal cancer, and 25 (83.3%) had liver metastases. In previous reports, ORR, DCR, and median PFS were 76.7%, 93.3%, and 11.3 months, respectively. At a Median follow-up of 31.7 months (95% CI, 27.8-35.6), the median OS was 29.7 months (95% CI, 21.2-38.2), the 24-month OS rate was 55.0% (95%CI, 35.4-70.9%) and the 30-month OS rate was 40.6% (95%CI:21.6-58.9%). Conclusions: Anlotinib combined with oxaliplatin and capecitabine achieved considerable OS and showed potential efficacy as first-line therapy for mCRC with manageable toxicity profiles. Clinical trial information: NCT04080843. Research Sponsor: None.||||

||N|81|75|||

|Total cohort|156|6.2 (5.4-10.7)|4.0 (3.1-4.2)|||

|Number of metastases*||||||

|Limited metastatic (1-10)|55|9.9 (6.1-12.6)|4.0 (2.3-6.6)|||

|Polymetastatic ( > 10)|49|4.1 (2.2-8.3)|2.3 (2.1-5.8)|||

|Total volume of metastases* Low tumor load ( < 40 cm 3 ) High tumor load ( > 40 cm 3 )|54 50|6.3 (5.8-12.0) 5.8 (3.8-12.5)|4.4 (2.3-6.2) 2.3 (2.1-4.8)|||

|*N=52 missing.||||||

|132|||Poster Session|||

|33.4 vs. 48.2 months; hazard ratio [HR], 1.52; p = 0.05; median PPS, 17.2 vs. 23.5 months;||||||

||135||||||Poster Session|Poster Session| |---|---|---|---|---|---|---|---|---|

||Amivantamab monotherapy in relapsed/refractory metastatic colorectal|Amivantamab monotherapy in relapsed/refractory metastatic colorectal|Amivantamab monotherapy in relapsed/refractory metastatic colorectal|Amivantamab monotherapy in relapsed/refractory metastatic colorectal|Amivantamab monotherapy in relapsed/refractory metastatic colorectal|Amivantamab monotherapy in relapsed/refractory metastatic colorectal|Amivantamab monotherapy in relapsed/refractory metastatic colorectal|Amivantamab monotherapy in relapsed/refractory metastatic colorectal|

||cancer: OrigAMI-1, an open-label, phase 1b/2 study. First Author:|cancer: OrigAMI-1, an open-label, phase 1b/2 study. First Author:|cancer: OrigAMI-1, an open-label, phase 1b/2 study. First Author:|cancer: OrigAMI-1, an open-label, phase 1b/2 study. First Author:|cancer: OrigAMI-1, an open-label, phase 1b/2 study. First Author:|cancer: OrigAMI-1, an open-label, phase 1b/2 study. First Author:|cancer: OrigAMI-1, an open-label, phase 1b/2 study. First Author:|cancer: OrigAMI-1, an open-label, phase 1b/2 study. First Author:|

||Paul Eliezer Oberstein, NYU Langone Health, New York, NY|Paul Eliezer Oberstein, NYU Langone Health, New York, NY|Paul Eliezer Oberstein, NYU Langone Health, New York, NY|Paul Eliezer Oberstein, NYU Langone Health, New York, NY|Paul Eliezer Oberstein, NYU Langone Health, New York, NY|Paul Eliezer Oberstein, NYU Langone Health, New York, NY|Paul Eliezer Oberstein, NYU Langone Health, New York, NY||

|Pts with|||||||||

|blood or tissue next generation sequencing (NGS) positive for a somatic BRCA1/2 variant|||||||||

|and a diagnosis of CRC were identified from a single institution database. The patho-genicity of each mutation was annotated using public genomic databases (e.g. ClinVar). Pt characteristics were compared using Fisher's exact test. Log-rank test was used for comparison of survival distribution among groups. Results: 8,258 NGS reports with a BRCA1/2 alteration from 1760 cancer pts were identified of which 189 (11%) had a di-agnosis of CRC. 54/189 CRC pts (29%) had $1 pathogenic BRCA1/2 variant, 19 pts (10%)|posure to anti-EGFR monoclonal antibodies, respectively, and cohort C included pts with right-sided mCRC. Safety population included all pts receiving the recommended phase 2 dose (RP2D; 1050 mg [1400 mg, $80kg]). Investigator-assessed response per RECIST v1.1 is reported for evaluable pts with post-baseline disease assessment(s) or who discontinued for any reason. Ami plus FOLFOX or FOLFIRI is being explored in additional cohorts. Results: As of September 4, 2023, 93 pts were treated at RP2D; 89 were response evaluable (median follow-up: 4.4 mo).|posure to anti-EGFR monoclonal antibodies, respectively, and cohort C included pts with right-sided mCRC. Safety population included all pts receiving the recommended phase 2 dose (RP2D; 1050 mg [1400 mg, $80kg]). Investigator-assessed response per RECIST v1.1 is reported for evaluable pts with post-baseline disease assessment(s) or who discontinued for any reason. Ami plus FOLFOX or FOLFIRI is being explored in additional cohorts. Results: As of September 4, 2023, 93 pts were treated at RP2D; 89 were response evaluable (median follow-up: 4.4 mo).|posure to anti-EGFR monoclonal antibodies, respectively, and cohort C included pts with right-sided mCRC. Safety population included all pts receiving the recommended phase 2 dose (RP2D; 1050 mg [1400 mg, $80kg]). Investigator-assessed response per RECIST v1.1 is reported for evaluable pts with post-baseline disease assessment(s) or who discontinued for any reason. Ami plus FOLFOX or FOLFIRI is being explored in additional cohorts. Results: As of September 4, 2023, 93 pts were treated at RP2D; 89 were response evaluable (median follow-up: 4.4 mo).|posure to anti-EGFR monoclonal antibodies, respectively, and cohort C included pts with right-sided mCRC. Safety population included all pts receiving the recommended phase 2 dose (RP2D; 1050 mg [1400 mg, $80kg]). Investigator-assessed response per RECIST v1.1 is reported for evaluable pts with post-baseline disease assessment(s) or who discontinued for any reason. Ami plus FOLFOX or FOLFIRI is being explored in additional cohorts. Results: As of September 4, 2023, 93 pts were treated at RP2D; 89 were response evaluable (median follow-up: 4.4 mo).|posure to anti-EGFR monoclonal antibodies, respectively, and cohort C included pts with right-sided mCRC. Safety population included all pts receiving the recommended phase 2 dose (RP2D; 1050 mg [1400 mg, $80kg]). Investigator-assessed response per RECIST v1.1 is reported for evaluable pts with post-baseline disease assessment(s) or who discontinued for any reason. Ami plus FOLFOX or FOLFIRI is being explored in additional cohorts. Results: As of September 4, 2023, 93 pts were treated at RP2D; 89 were response evaluable (median follow-up: 4.4 mo).|posure to anti-EGFR monoclonal antibodies, respectively, and cohort C included pts with right-sided mCRC. Safety population included all pts receiving the recommended phase 2 dose (RP2D; 1050 mg [1400 mg, $80kg]). Investigator-assessed response per RECIST v1.1 is reported for evaluable pts with post-baseline disease assessment(s) or who discontinued for any reason. Ami plus FOLFOX or FOLFIRI is being explored in additional cohorts. Results: As of September 4, 2023, 93 pts were treated at RP2D; 89 were response evaluable (median follow-up: 4.4 mo).|posure to anti-EGFR monoclonal antibodies, respectively, and cohort C included pts with right-sided mCRC. Safety population included all pts receiving the recommended phase 2 dose (RP2D; 1050 mg [1400 mg, $80kg]). Investigator-assessed response per RECIST v1.1 is reported for evaluable pts with post-baseline disease assessment(s) or who discontinued for any reason. Ami plus FOLFOX or FOLFIRI is being explored in additional cohorts. Results: As of September 4, 2023, 93 pts were treated at RP2D; 89 were response evaluable (median follow-up: 4.4 mo).|posure to anti-EGFR monoclonal antibodies, respectively, and cohort C included pts with right-sided mCRC. Safety population included all pts receiving the recommended phase 2 dose (RP2D; 1050 mg [1400 mg, $80kg]). Investigator-assessed response per RECIST v1.1 is reported for evaluable pts with post-baseline disease assessment(s) or who discontinued for any reason. Ami plus FOLFOX or FOLFIRI is being explored in additional cohorts. Results: As of September 4, 2023, 93 pts were treated at RP2D; 89 were response evaluable (median follow-up: 4.4 mo).|

|had $1 benign variant, and 134 pts (69%) had 1 $ variant of unknown significance (VUS);|Median age was 60 years, 66% were male, and median prior lines of therapy were 2, with 94%|Median age was 60 years, 66% were male, and median prior lines of therapy were 2, with 94%|Median age was 60 years, 66% were male, and median prior lines of therapy were 2, with 94%|Median age was 60 years, 66% were male, and median prior lines of therapy were 2, with 94%|Median age was 60 years, 66% were male, and median prior lines of therapy were 2, with 94%|Median age was 60 years, 66% were male, and median prior lines of therapy were 2, with 94%|Median age was 60 years, 66% were male, and median prior lines of therapy were 2, with 94%|Median age was 60 years, 66% were male, and median prior lines of therapy were 2, with 94%|

|26 pts (14%) had more than one BRCA1/2 variant. Pts with $1 pathogenic mutation (n=54)|receiving prior bevacizumab and 69% prior anti-EGFR therapy. Best timepoint responses were:|receiving prior bevacizumab and 69% prior anti-EGFR therapy. Best timepoint responses were:|receiving prior bevacizumab and 69% prior anti-EGFR therapy. Best timepoint responses were:|receiving prior bevacizumab and 69% prior anti-EGFR therapy. Best timepoint responses were:|receiving prior bevacizumab and 69% prior anti-EGFR therapy. Best timepoint responses were:|receiving prior bevacizumab and 69% prior anti-EGFR therapy. Best timepoint responses were:|receiving prior bevacizumab and 69% prior anti-EGFR therapy. Best timepoint responses were:|receiving prior bevacizumab and 69% prior anti-EGFR therapy. Best timepoint responses were:|

|were more likely to have an inactivating DNA polymerase epsilon (POLE) mutation versus|Cohort A: 7/17, 41.2%; Cohort B: 13/54, 24.1%; Cohort C: 1/18, 5.6%. Disease control rates (DCR)|Cohort A: 7/17, 41.2%; Cohort B: 13/54, 24.1%; Cohort C: 1/18, 5.6%. Disease control rates (DCR)|Cohort A: 7/17, 41.2%; Cohort B: 13/54, 24.1%; Cohort C: 1/18, 5.6%. Disease control rates (DCR)|Cohort A: 7/17, 41.2%; Cohort B: 13/54, 24.1%; Cohort C: 1/18, 5.6%. Disease control rates (DCR)|Cohort A: 7/17, 41.2%; Cohort B: 13/54, 24.1%; Cohort C: 1/18, 5.6%. Disease control rates (DCR)|Cohort A: 7/17, 41.2%; Cohort B: 13/54, 24.1%; Cohort C: 1/18, 5.6%. Disease control rates (DCR)|Cohort A: 7/17, 41.2%; Cohort B: 13/54, 24.1%; Cohort C: 1/18, 5.6%. Disease control rates (DCR)|Cohort A: 7/17, 41.2%; Cohort B: 13/54, 24.1%; Cohort C: 1/18, 5.6%. Disease control rates (DCR)|

|pts with only benign/VUS BRCA1/2 variants (n=135) (20% vs 6%, p=0.004) while prevalence|were 88.2%, 72.2%, and 77.8% for Cohorts A, B, and C, respectively. Median duration of response|were 88.2%, 72.2%, and 77.8% for Cohorts A, B, and C, respectively. Median duration of response|were 88.2%, 72.2%, and 77.8% for Cohorts A, B, and C, respectively. Median duration of response|were 88.2%, 72.2%, and 77.8% for Cohorts A, B, and C, respectively. Median duration of response|were 88.2%, 72.2%, and 77.8% for Cohorts A, B, and C, respectively. Median duration of response|were 88.2%, 72.2%, and 77.8% for Cohorts A, B, and C, respectively. Median duration of response|were 88.2%, 72.2%, and 77.8% for Cohorts A, B, and C, respectively. Median duration of response|were 88.2%, 72.2%, and 77.8% for Cohorts A, B, and C, respectively. Median duration of response|

|of microsatellite instability (MSI-H) (19% vs 13%, p=0.37) and Ras/Raf (53% vs 53%,|(mDoR) for confirmed responders was 7.5 and 7.4 mo for Cohorts A and B, respectively. Treatment|(mDoR) for confirmed responders was 7.5 and 7.4 mo for Cohorts A and B, respectively. Treatment|(mDoR) for confirmed responders was 7.5 and 7.4 mo for Cohorts A and B, respectively. Treatment|(mDoR) for confirmed responders was 7.5 and 7.4 mo for Cohorts A and B, respectively. Treatment|(mDoR) for confirmed responders was 7.5 and 7.4 mo for Cohorts A and B, respectively. Treatment|(mDoR) for confirmed responders was 7.5 and 7.4 mo for Cohorts A and B, respectively. Treatment|(mDoR) for confirmed responders was 7.5 and 7.4 mo for Cohorts A and B, respectively. Treatment|(mDoR) for confirmed responders was 7.5 and 7.4 mo for Cohorts A and B, respectively. Treatment|

|p=1.00) were similar between groups. Median progression free survival (PFS) among 115 CRC pts (unselected for BRCA1/2 pathogenicity) who received an oxaliplatin-based regimen for advanced disease in the 1 st line (n=52) was similar to the median PFS among pts who received an irinotecan-based regimen (n=63) (7.0 mths vs 7.0 mths, With a global median follow-up of 16.5 mo, the crude PFS was 6.8 (95% CI: 4.3-11.3) mo in FP cohort vs. 3.9 (3.1-4.7) mo in FM cohort. The HR of FP was 0.58 (95% CI: 0.34-0.98, FM as reference). Multivariate Cox regression showed that the adjusted HR was 0.49 (95%|is ongoing for the responder in Cohort C. 10/13 responders (77%) remain on treatment. Pre-liminary biomarker data suggest ami may be active in alterations associated with anti-EGFR antibody resistance (eg, Efficacy.|is ongoing for the responder in Cohort C. 10/13 responders (77%) remain on treatment. Pre-liminary biomarker data suggest ami may be active in alterations associated with anti-EGFR antibody resistance (eg, Efficacy.|is ongoing for the responder in Cohort C. 10/13 responders (77%) remain on treatment. Pre-liminary biomarker data suggest ami may be active in alterations associated with anti-EGFR antibody resistance (eg, Efficacy.|is ongoing for the responder in Cohort C. 10/13 responders (77%) remain on treatment. Pre-liminary biomarker data suggest ami may be active in alterations associated with anti-EGFR antibody resistance (eg, Efficacy.|is ongoing for the responder in Cohort C. 10/13 responders (77%) remain on treatment. Pre-liminary biomarker data suggest ami may be active in alterations associated with anti-EGFR antibody resistance (eg, Efficacy.|is ongoing for the responder in Cohort C. 10/13 responders (77%) remain on treatment. Pre-liminary biomarker data suggest ami may be active in alterations associated with anti-EGFR antibody resistance (eg, Efficacy.|is ongoing for the responder in Cohort C. 10/13 responders (77%) remain on treatment. Pre-liminary biomarker data suggest ami may be active in alterations associated with anti-EGFR antibody resistance (eg, Efficacy.|is ongoing for the responder in Cohort C. 10/13 responders (77%) remain on treatment. Pre-liminary biomarker data suggest ami may be active in alterations associated with anti-EGFR antibody resistance (eg, Efficacy.|

|||||Best timepoint||mDoR|Median|Median duration|

||Cohort|Details|n|response, % (n/N) DCR (%)|(mo)*|PFS (mo)|of treatment (mo)*||

||A B C|L-sided, no anti-EGFR 17 L-sided, post anti-EGFR 54 R-sided, 6 anti-EGFR 18|41.2 (7/17) † 24.1 (13/54) ‡ 5.6 (1/18) §|88.2 72.2 77.8|7.5 7.4 Not estimable|5.7 3.75 3.5|8.3 5.55 5.5||

|136 7/22/22 and 9/7/23,15 pts with MRD were enrolled. Baseline characteristics included a Poster Session Results: Between median age of 62 years (range: 37-73), Caucasian (77%), male (77%), resected Stage IV (92%) and median ctDNA level of 1.55 MTM/ml (range 0.04-28.72). At data cutoff, 11 pts had 3-m ctDNA levels and 10 had a decrease in their ctDNA level (91%) including 5 with undetectable levels (45%). At 6-m, 60% of patients had ctDNA levels at or below prior levels; three maintained undetectable ctDNA at 6-m: of those, two pts had subsequent radiographic progression following therapy completion. Median DFS was 9.4-m in the full cohort. 137 61 years (23-82), and 27 pts (50.9%) were females. Twenty-two pts (41.5%) had their Poster Session was primary tumor located in the left colon, 17 pts (32.1%) had right-sided tumors, and 14 pts (26.4%) with rectal tumors. 52% of pts received TAS-102 after 2 lines of therapy and 43% beyond third line. The performance status was: ECOG 0/1 in 46 pts (86.8%), and ECOG 2 in 7 pts (13.2%). In our refractory mCRC pts, median PFS was 3 months and median OS 7 months. Univariate analysis demonstrated no significant differences in PFS or OS based on patient sex, KRAS mutation status, tumor sidedness, or the number of prior treatments. In univariate and multivariate analysis ECOG 0/1 pts compared to ECOG 2 pts had a significant improvement in both PFS (HR = 0.33; p = 0.0511) and OS (HR = 0.21; p = 0.0086). Conclusions: In our real-world experience, clinical outcomes were com-parable to the findings from the RECOURSE trial, suggesting improved PFS and OS with|||||||||

|||||144|Poster Session| |---|---|---|---|---|---|

|||||Methods: Patients with clinically staged II-III rectal cancer were treated with preop-|Methods: Patients with clinically staged II-III rectal cancer were treated with preop-|

|||||erative CT/RT using up to 3 cycles of oxaliplatin and fluoropyrimidine plus pelvic ra-|erative CT/RT using up to 3 cycles of oxaliplatin and fluoropyrimidine plus pelvic ra-|

|||Disease Control Rate (DCR)|diation daily, for a total dose of 46.2 Gy in 18 fractions. The first cycle of mXELOX|diation daily, for a total dose of 46.2 Gy in 18 fractions. The first cycle of mXELOX||

|was also determined. Results: As of 31Aug2023, 36 pts with advanced mCRC were|(oxaliplatin 85 mg/m2 D1 Q14 plus capecitabine 825 mg/m2 BID) was administrated|(oxaliplatin 85 mg/m2 D1 Q14 plus capecitabine 825 mg/m2 BID) was administrated||||

|treated. Median age was 62 years (range 40-78), 56% were women, all pts were ECOG 0|before RT (as induction CT); the other 2 cycles of mXELOX were administrated con-|before RT (as induction CT); the other 2 cycles of mXELOX were administrated con-||||

|(25%) or 1 (75%). Enrolled pts had a median of 4 prior systemic therapies, including|current with RT, with capecitabine continued until the end of RT. Radical resection was|current with RT, with capecitabine continued until the end of RT. Radical resection was||||

|FOLFOX/CAPOX. All but one patient had stage IV disease. On study, pts received a|performed within median 11 weeks of the last dose of RT. Adjuvant CT with FOLFOX or|performed within median 11 weeks of the last dose of RT. Adjuvant CT with FOLFOX or||||

|median of 6 cycles of BOLD-100 + FOLFOX [range 1-17]. Five pts remain on treatment|XELOX was administered according to pathological report. Results: Between 2007 and|XELOX was administered according to pathological report. Results: Between 2007 and||||

|with 19 in follow-up. Median PFS was 3.9 [2.7, 5.7] months, median OS 9.6 [6.0, 17]|2022, a total of 186 patients were enrolled, mean age was 61 years. 19 (10.2%) patients|2022, a total of 186 patients were enrolled, mean age was 61 years. 19 (10.2%) patients||||

|months, ORR 7% [1,20] and DCR 76% [58, 88] in the 29 evaluable pts. Two pts achieved a|were clinically stage II and 167 (89.8%) were clinically stage III. Any grade most common|were clinically stage II and 167 (89.8%) were clinically stage III. Any grade most common||||

|partial response, and 2 pts had target tumor lesion decreases between 20-29%. Study|toxicities during neoadjuvant CT/RT included diarrhea (53.2%), proctitis (51.2%) and|toxicities during neoadjuvant CT/RT included diarrhea (53.2%), proctitis (51.2%) and||||

|treatment was well tolerated. Of the 36 treated pts, 33 had 1 or more treatment-|neutropenia (14.5%). The most common grade 3/4 toxicity was diarrhea (9.1%). A total|neutropenia (14.5%). The most common grade 3/4 toxicity was diarrhea (9.1%). A total||||

|emergent adverse events (AEs), most common neutropenia (n=17, 47%), nausea (n=15,|of 146 (78.5%) patients achieved a downstaging after CT/RT and 174 (93.5%) patients|of 146 (78.5%) patients achieved a downstaging after CT/RT and 174 (93.5%) patients||||

|42%), vomiting (n=8, 22%), fatigue (n=7, 19%), infusion related reaction (n=7, 19%), and|underwent surgery with R0 resection. Clinical meaningful surgical morbidities included|underwent surgery with R0 resection. Clinical meaningful surgical morbidities included||||

|142 infections (10.145 pruritus (n=6, 17%). Most related AEs were grade (G) 1-2. 15 pts (42%) had G3/4 neutropenia. Despite previous oxaliplatin treatment, fewer than 6% of pts reported peripheral neuropathy or peripheral sensory neuropathy and all were G1/2. Poster Session|Poster Session|||||

|||||Patients with ETS $ 20% and DpR $ 25% (median value) were 24 (44.4%) and 27 (50%)|Patients with ETS $ 20% and DpR $ 25% (median value) were 24 (44.4%) and 27 (50%)|

|||||respectively. PFS was 7.5 months (95% confidence interval (CI), 5.0-9.9) and OS was|respectively. PFS was 7.5 months (95% confidence interval (CI), 5.0-9.9) and OS was|

|||||17.1 months (95% CI, 11.7-20.2). Patients with ETS $ 20% had longer PFS and tended to|17.1 months (95% CI, 11.7-20.2). Patients with ETS $ 20% had longer PFS and tended to|

|||||have longer OS than those with non-ETS, with a median PFS of 9.8 months vs.|have longer OS than those with non-ETS, with a median PFS of 9.8 months vs.|

|||||4.8 months (P Log-rank = 0.048, hazard ratio (HR), 0.55; 95% CI, 0.30-1.00), and a median|4.8 months (P Log-rank = 0.048, hazard ratio (HR), 0.55; 95% CI, 0.30-1.00), and a median|

|||||OS of 22.6 months vs. 11.6 months (P Log-rank = 0.18, HR, 0.67; 95% CI, 0.37-1.21).|OS of 22.6 months vs. 11.6 months (P Log-rank = 0.18, HR, 0.67; 95% CI, 0.37-1.21).|

||SORRECT|ReDOS|Moscow 62 RWD|Patients with DpR $ 25% had also longer PFS and OS than those with non-DpR, with a|Patients with DpR $ 25% had also longer PFS and OS than those with non-DpR, with a|

|All patients|505|54|311|||

|Median Age|61|62|61|||

|Male|62%|67%|50.5%|||

|Female|38%|33%|49.5%|||

|Colon cancer|64%||70.1%|||

|Rectal cancer|30%||29.9%|||

|KRAS mut|54%|39%|46%|||

|BRAF mut|4%|0%|3.8%|||

|WT|37%|N/A|46%|||

|> / 3 lines of therapy|64%|67%|93.5%|||

|ECOG 0/1/2-3|52%/48%/N/A|37%/63%/N/A|11%/57.8%/31.2%|||

|(ClinicalTrials.gov No.: NCT04543695). Patients aged 18-75 years with initial stage II / III rectal adenocarcinoma ( At least one of high-risk factors should be included: mesorectal fascia involvement, T4, N2, positive lateral lymph node, or extramural vessel invasion) were assigned into three groups, 1) Chemoradiotherapy (50 Gy of radiation combined with oral capecitabine) followed by consolidation chemotherapy using six cycles of XELOX(CNCT group), 2) Induction chemotherapy before chemoradiotherapy (INCT group), or 3) Chemoradiotherapy alone (Control group). Then enrolled patients were required to undergo radical surgery after neoadjuvant therapy. Patients in Control group need six cycles of XELOX after surgery. The primary end point was proportion of yp0-II, and watch-and-wait strategy after complete clinical response (cCR) was allowed. Results: Of the 257 patients enrolled, 255 patients were evaluable (Control: CNCT: INCT= 84: 86: 85). Neoadjuvant treatment related grade 3 or 4 toxicity was higher in TNT approach (7.1%, 23.3% and 32.9% in Control, CNCT and INCT, respectively), of with myelosuppression being most common. Compliance of chemoradiotherapy was lower in INCT group (98.8%, 100% and 90.6% in Control, CNCT and INCT, respectively). As to CNCT and INCT, 60.0% and 74.1% of patients completed six cycles of chemotherapy, Genome-wide DNA methylation status to predict the efficacy of modified (m)-FOLFOXIRI plus cetuximab as initial treatment for RAS wild-type met-astatic colorectal cancer: A biomarker study of the DEEPER trial (JACCRO CC-13AR). First Author: Kota Ouchi, Department of Medical Oncology, Tohoku Uni-versity Hospital, Sendai, Japan Background: Genome-wide DNA methylation status (GWMS) has been shown to be a predictor of therapeutic response to anti-EGFR antibody therapies. This study inves-tigated the association between GWMS and clinical outcomes of first-line chemotherapy with anti-EGFR or anti-VEGF antibody agents for metastatic colorectal cancer (mCRC). Methods: Tumor tissues of mCRC patients registered in the JACCRO CC-13AR (clinical trial number: UMIN000018412) were analyzed for GWMS and were classified into low-methylated colorectal cancer (LMCC) and high-methylated colorectal cancer (HMCC). Clinical data were obtained from the randomized phase II trial, DEEPER trial (JACCRO CC-13) [NCT02515734] , in which patients were randomly assigned to m-FOLFOXIRI plus cetuximab (CET) arm and m-FOLFOXIRI plus bevacizumab (BEV) arm for treatment. Progression-free survival (PFS), overall survival (OS), depth of response (DpR), and response rate (RR) were analyzed according to GWMS for each treatment arm. with 76.7% and 83.148 Early identification and treatment of occult metastatic disease in stage III Poster Session colon cancer (SU2C ACT3 clinical trial). First Author: Leon Pappas, Department of Medicine, Division of Hematology & Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA quencing panel (Reveal, Guardant Health). A baseline CT scan is required to confirm lack of metastases. Pts with undetectable ctDNA (-) at screening undergo surveillance with imaging, labs and ctDNA testing every 3 months (Arm 3). ctDNA-detectable (+) pts who are biomarker-negative are randomized to 1:1 to FOLFIRI (Arm 1) or active surveillance (Arm 2). ctDNA+ pts with an actionable biomarker (biomarker-positive) are given 6 months biomarker-directed therapy as follows: V600E/MSS-encorafenib, binimetinib and cetuximab (Arm 5), HER2 am-plified trastuzumab/pertuzumab (arm 6), and MSI-H nivolumab (Arm 4). Primary outcome is ctDNA clearance in Arms 1 and 2, 1-month after completion of additional adjuvant therapy or 153 Poster Session Characterizing differential efficacy and phenotypic response to proteasome and survivin inhibitors in colorectal cancers using a high throughput orga-noid assay. First Author: Dana Zuaiter, CerFlux, Inc., Birmingham, AL Background: Conventional monolayer cell cultures and xenograft models, while useful and economical in early drug discovery, cannot predict clinical efficacy. Further, pre-clinical screening assays that rely on differential metabolic activity between separate control and treated wells are incapable of capturing phenotypic response and could overstate efficacy for cells with high rates of proliferation. Consequently, over 95% of anticancer agents that show efficacy in preclinical studies, fail in clinical trials. Recently, patient-derived organoid (PDO) models have been utilized in developing platforms to predict clinical efficacy of preclinical formulations. If successful, such predictive ex vivo technologies could revolutionize cancer treatment by reducing cost and time-to-market for new, more effective therapeutics. Objective: Characterize a novel bioprinted organoid tumor (BOT) high-throughput screening ex vivo platform for drug response prediction (DRP) with known proteosome and survivn inhibitors in colorectal cancer. Methods: Bioink for 3D printing BOTs was prepared with HT-29 cells, an established NCI-60 human colorectal adenocarcinoma cell line with known sensitivity to proteosome Results: One hundred thirty-seven out of 227 patients enrolled in the JACCRO CC-13AR were analyzed. Of these, 122 (89.1%) and 15 (10.9%) were classified in the LMCC and HMCC, respectively; 66 were assigned to the CET arm including 7 HMCCs, and 54 were assigned to the BEV arm including 8 HMCCs. In the CET arm, PFS and OS of the LMCC were significantly longer than those of the HMCC (median PFS 14.3 vs. 4.0 months, hazard ratio [HR] 0.11, 95% CI: 0.05-0.29, P,0.01; median OS 42.7 vs. 13.6 months, HR 0.04, 95% CI: 0.01-0.13, P,0.01). There were no differences in DpR and RR between the LMCC and the HMCC (median DpR 58.1% vs. 46.7%, P=0.45), although RR of the LMCC was numerically higher than that of the HMCC (71.2% vs. 42.9%, P=0.13). In contrast, in the BEV arm, there were no differences in PFS, DpR, and RR between the two groups (median PFS 16.1 vs. 12.2 months, P=0.08; median DpR 48.3% vs. 53.9%, P=0.99; RR 73.0% vs. 75.0%, P=0.91). However, OS of the LMCC was significantly longer than that of the HMCC (median OS 48.9 vs. 24.2 months, HR 0.39, 95% CI: 0.16-0.95, P=0.03). Conclusions: This study showed that GWMS may be a prognostic marker for initial treatment in RAS wild-type mCRC. Also, GWMS correlates to the survival outcomes of m-and survivin inhibitors. Bioink was deposited layer-by-layer on multiple substrates, in various geometrical configurations, and cured in stages to allow cells and matrix to self-assemble with limited degrees of freedom. BOTs were screened 24h and 48h after printing with proteosome inhibitor Bortezomib and survivin inhibitor YM-155. BOTs were evaluated 48h and 72h after treatment using immunofluorescence live/dead assay. Morphological phenotypic changes resulting from treatment were also recorded. Results: Proteasome and survivin inhibitors have been reported to inhibit proliferation and induce cell death in colorectal cancer cells. A dose dependent response was observed for both agents in our novel BOT HTS thereby validating the platform. In addition, characteristic self-assembly of HT-29 cells was observed to be disrupted at effective doses and at certain concentrations below the effective dose. Traditional ATP assays are incapable of recording such phenotypic modulation. Further, a higher proliferation profile was observed in untreated BOTs suggesting that use of independent control wells in traditional assays could overstate efficacy of treatment. Conclusions: Functional high-throughput ex vivo DRP technologies have the potential surveillance. Patient distribution in the SU2C ACT3 study. FOLFOXIRI plus CET as initial treatment for RAS wild-type mCRC. Clinical trial infor-to transform cancer treatment -from bench to bedside -along the drug discovery to||||||||||||||| |---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|

|mation: 000018412. Research Sponsor: Japan Clinical Cancer Research Organization.|Total market roadmap for much needed novel anticancer agents. Research Sponsor: NSF. Pre-Screen Off ctDNA Treatment Arm||||||||||||||

||||Screened|Screening|Fail|Enrolled|Study|+|-Arm 1 Arm 2 Arm 3 Arm 4 Arm 5 Arm 6||||||

||||147|8|6 6|7 3|1 0|1 0 6 3|4|5|6 3|1|0|0|

|149 154||Poster Session Poster Session|150|||||||||Poster Session|||

|Genomic alteration in sporadic adolescent and young adult-onset colorectal|Enrichment of circulating helper-T (Th) and unswitched memory-B (NSwM-||||||||||||||

|adenocarcinoma. First Author: Krittiya Korphaisarn, Faculty of Medicine Siriraj|B) cell populations and responsiveness to immune checkpoint blockade||||||||||||||

|Hospital, Mahidol University, Bangkoknoi, Thailand||(ICB) in microsatellite-stable (MSS)/mismatch repair-proficient (pMMR)|||||||||||||

|Background: Colorectal cancer (CRC) incidence is increasing in adults younger than 50 years. This study evaluated genomic alteration in adolescent and young adult (AYA)-|colorectal cancer (CRC). First Author: Sebastian Meltzer, Akershus University Hospital, Lorenskog, Norway||||||||||||||

|onset sporadic CRC patients who aged between 15 and 39 years. Methods: DNA from 90|Background: The anti-tumor activity of ICB in MSS/pMMR-CRC is limited. However, recent||||||||||||||

|archived formalin-fixed, paraffin-embedded (FFPE) tissue samples that histologically|studies have highlighted the possibility of inducing ICB responsiveness by oxaliplatin-based||||||||||||||

|confirmed adenocarcinoma with proficient mismatch repair tumors at Siriraj Hospital|chemotherapy. The understanding of underlying mechanisms and identification of rational||||||||||||||

oreover, multivariate analysis revealed that EGJA and GA had a|

|Methods: We| |---|

|portional hazards models. Results: In this study, 398 patients received neoadjuvant DCF|

|therapy and we identified 88 eligible patients with recurrence. Among 88 patients, 33|

|patients initially received palliative chemotherapy and analyzed. Patients' character-|

|istics were followed; Male/Female: 26 (78.8%)/7 (21.2%), median age (range): 64 (46-76)|

|years, PS 0/1/2: 1 2(36.4%)/17 (51.5%), 4 (12.1%). Histopathological response 0/1/2/3|

|were in 1 (3.0%)/23 (69.7%)/7 (21.2%)/2 (6.1%) patients, respectively. Among these 33|

|patients, 23 patients received platinum-containing regimens. In the patients who re-|

|ceived palliative chemotherapy, the ORR were 34.8% (8/23) in histopathological re-|

|sponse 0/1 group and 44.4% (4/9) in histopathological response 2/3 group, with no|

information: NCT003388190. Research Sponsor: None.||||||||||||

|||157|||Poster Session|Poster Session| |---|---|---|---|---|---|---|

|between ctDNA assays. Patients with a subsequent ctDNA assay after therapy initiation|||||||

|were included for analysis of acquired alterations. Results: Of 2801 pts, 1308 (47%)|||||||

|harbored $1 MAPK alteration in their first ctDNA timepoint and were excluded from|||||||

|analysis. Of the remaining 1493 without a MAPK alteration prior to therapy, 588 (39.4%)|||||||

|had a MAPK alteration detected in a subsequent ctDNA timepoint. Among 447 of 1493|||||||

|pts (31.8%) with subsequent exposure to anti-EGFR antibodies, acquisition of a MAPK|||||||

|alteration occurred in 229/447 (51.2%). This was more common (OR 2.01. 95% CI 1.61-|||||||

|2.51, P,0.0001) than in patients without exposure to anti-EGFR antibodies (359/1046|||||||

|[34.3%]). Acquired MAPK alterations were more common among those receiving single|||||||

|agent antibodies (42/66, 63.6%) than anti-EGFR plus chemotherapy (187/381, 49.1%)|||||||

|(OR 1.82, 95% CI 1.05-3.08, P=0.030). Patients with anti-EGFR antibody exposure were|||||||

|found to have higher blood TMB scores in the first assay after treatment compared to|||||||

|patients treated with chemotherapy alone (11.5 vs. 8.8 mut/MB, respectively; P=0.001),|||||||

|with no significant blood TMB difference between those receiving single agent anti-|||||||

|EGFR versus anti-EGFR plus chemotherapy (median 12.4 vs. 11.5 mut/MB; P=0.52).|||||||

|Patients who acquired MAPK alterations after anti-EGFR therapy had higher blood TMB|||||||

|scores compared to patients who did not acquire MAPK alterations (median 14.3 vs 8.6|||||||

|mut/MB, respectively; p,0.0001). Conclusions: In this large cohort of pts with mCRC|||||||

|and treatment information, we demonstrate serial ctDNA identified a large proportion of|||||||

|patients acquiring resistance alterations that may impact response to future therapies.|||||||

|These results suggest serial ctDNA analysis may provide additional molecular insights|||||||

|for patients receiving anti-EGFR therapy and inform future anti-EGFR rechallenge|||||||

|strategies. Research Sponsor: Guardant Health.|||||||

|40s|COLORECTAL CANCER||| |---|---|---|---|

|||161 165 169|Poster Session Poster Session Poster Session|

|Tumoral microbial and pathway alterations associated with young-onset Comparison of colorectal cancer (CRC) characteristics across genetic an-Association of class II and III BRAF mutations with EGFR blockade therapy|Identification and characterization of immunogenic neoantigens in colo-Liver steatosis and fibrosis as independent prognostic factors affecting Clonal hematopoiesis of indeterminate potential (CHIP), treatment out-|Identification and characterization of immunogenic neoantigens in colo-Liver steatosis and fibrosis as independent prognostic factors affecting Clonal hematopoiesis of indeterminate potential (CHIP), treatment out-||

|rectal cancer and its response to therapy. First Author: Michael White, The cestries: Implications for early cancer detection (ECD). First Author: Parvathi response and representation of molecularly distinct subgroups of BRAF|rectal cancer (CRC). First Author: Francesca Battaglin, Norris Comprehensive Cancer survival in colorectal cancer with liver metastases. First Author: Nikhil Gupta, comes and adverse events in gastrointestinal cancers: A pooled analysis|rectal cancer (CRC). First Author: Francesca Battaglin, Norris Comprehensive Cancer survival in colorectal cancer with liver metastases. First Author: Nikhil Gupta, comes and adverse events in gastrointestinal cancers: A pooled analysis||

|University of Texas MD Anderson Cancer Center, Houston, TX Myer, Albert Einstein Cancer Center, New York, NY mutations in MMR proficient CRC. First Author: Ibrahim Halil Sahin, University of|Center, Keck School of Medicine, University of Southern California, Los Angeles, CA Case Western Reserve University, Cleveland, OH of clinical trial and real-world data. First Author: Tharani Krishnan, BC Cancer -|Center, Keck School of Medicine, University of Southern California, Los Angeles, CA Case Western Reserve University, Cleveland, OH of clinical trial and real-world data. First Author: Tharani Krishnan, BC Cancer -||

|Background: Given the increasing incidence of young onset rectal cancer (YORC) in recent Background: Blood-based ECD has the potential to reduce mortality rates by improving Pittsburgh Medical Center, Pittsburgh, PA|Background: Presentation of neoantigens, short peptides derived from tumor-specific so-Background: Colorectal cancer is one of the leading causes of cancer-related death, and Vancouver, Vancouver, BC, Canada|Background: Presentation of neoantigens, short peptides derived from tumor-specific so-Background: Colorectal cancer is one of the leading causes of cancer-related death, and Vancouver, Vancouver, BC, Canada||

|decades, we examined the potential of tumor and fecal microbiome pathways in YORCs as strategies for, adoption of, and adherence to screening. A deeper understanding of the cancer Background: BRAF mutations (mts) represent a highly heterogeneous group of molecular|matic mutations, by HLA molecules triggers the activation of anti-tumor immune response. the liver represents the most common site of metastases. Greater depth of tissue Background: Clonal hematopoesis of indeterminate potential (CHIP) is the acquisition of somatic|matic mutations, by HLA molecules triggers the activation of anti-tumor immune response. the liver represents the most common site of metastases. Greater depth of tissue Background: Clonal hematopoesis of indeterminate potential (CHIP) is the acquisition of somatic||

|compared to late-onset rectal cancers (LORCs) while also exploring markers of response to neoadjuvant therapy (NAT). We hypothesize microbial markers reflect unique and po-tentially causative biology in YORC, and variability in response to NAT. Methods: Treatment-naïve patients with YO-(,50 years old) or LO-$50 years old) rectal cancers were prospectively enrolled. Tumor and tumor-adjacent normal tissues (TANs) were collected via endoscopic biopsy, as well as stool at baseline. After whole genome se-quencing, metagenomic analysis was performed using MetaPhlAn4, VirMAP and HUMAnN3 for taxonomical and metabolomic profiling. Association of microbial and immune signatures were examined comparing tumors vs. TANs, and YO-vs. LORC tumors. Differential abundance analyses were performed using paired Wilcoxon test and MaAsLin2. Molecular subtype defined for tissues with whole transcriptomic sequencing available. Results: 162 tumors and paired normal tissues, 73 (45.1%) YO-and 89 (54.9%) LORC were analyzed. Additional whole transcriptomic sequencing was available for 88 patients. The majority 145 (89.5%) of patients received neoadjuvant therapy. Observed bacterial di-versity was higher in tumors as compared to tumor associated normal (TAN) tissue (p,0.001). Moreover, bacterial diversity also increased linearly with age of diagnosis in tumors (p=0.01), but not TAN (p=NS). Oral bacteria previously associated with colorectal cancer were noted in these rectal cancers including Fusobacterium nucleatum (q,0.001) and Parvimonas micra (q,0.001). Escherichia coli, previously associated with colorectal cancer and development of metastatic disease was associated with YORC (q,0.001) but not LORC. For NAT treated patients, major pathologic response in YORC was associated with higher bacterial diversity (p=0.03) but not in LORC (p=NS). Similarly, no significant bacterial marker of response to neoadjuvant therapy was noted in LORC. While Butyr-icimonas virosa (q,0.001), Alistipes shahi (q=0.01), and Parabacteroides merdae (q=0.01) were all associated with a diminished pathologic response. Conclusions: Oral bacterial signatures previously associated with colorectal cancer were noted in both YORC and LORC when comparing matched tumor and TAN. Importantly, several unique bacterial associations were identified with YORC, including Escherichia Coli -previously associated with development of metastases in CRC. We also noted distinct microbial associations related to response to therapy in YORC suggesting the unique biology of these tumors. Functional bacterial pathway associations with response suggest a potential to augment NAT with existing or next-generation microbial modulation strategies. Research Sponsor: Cancer Alliance Chris4Life; National Institutes of Health. *p,0.05, **p,0.001 The University of Texas MD Anderson Cancer Center Moon Shots Program; Colorectal genomic landscape across genetic ancestries will aid comparable detection performance across a broad population. We evaluated the mutational landscape in patients with CRC across genetic ancestries. Methods: 16,080 de-identified patients with stage I-IV CRC who had personalized, tumor-informed commercial ctDNA testing (Signatera) based on whole exome sequencing (WES) were included. Genetic ancestry determined via supervised local ancestry inference (pmid36042219) included African (AFR), East Asian (EAS), European (EUR), Latino (LAT), and South Asian (SAS). Patients assigned to a single ancestry were included (except SAS due to small cohort size). Somatic single nucleotide variants called from WES were used for mutational signature inference. EUR was the reference group for standard statistical tests with corrections for multiple hypothesis testing. Results: A single genomic ancestry was assigned for 16,257 (99.2%) patients (AFR n=1697, 10%; EAS n=2247, 14%; EUR n=10,526, 64%; LAT n=1291, 1%; SAS n=184, 1%). Across AFR, EAS, EUR, and LAT, ap-proximately half of patients were male (range, 47-54%) and most were aged .50 years. Microsatellite instability (MSI) rates were significantly higher in EUR (14.5%) v AFR (11%, p,0.001), EAS (8%, p,0.001), and LAT (11%, p=0.002). Compared to EUR (range 0.027-875.1 mut/Mb), the distribution of TMB was significantly higher in EAS (0.304-906.2 mut/Mb, p,0.001) and lower in LAT (0.053-476.7 mut/Mb, p,0.001). The POLE hyper-mutator signature was seen in 1.2% of all patients and in 7.6% of all hyper-mutated cases. Pa-tients with the POLE signature were less common in EUR (1.1%) v AFR (2%, p=0.001). There were significant differences in the frequency of driver mutations in APC, BRAF, KRAS, TP53, alterations seen in colorectal cancer (CRC). Class I BRAF mts (V600) render aggressive biology to CRC and poor response to anti EGFR inhibitors. Currently there are limited data on clinical and molecular features of class II and III BRAF mts. In this study, we investigated the clinical and molecular characteristics of BRAF mutation classes and their impact on clinical outcomes in a large cohort of patients (pts) with mismatch proficient (pMMR) CRC. Methods: A total of 18575 pMMR CRC specimens were profiled by next-generation se-quencing (592-gene, NextSeq; WES, WTS NovaSeq) (Caris Life Sciences, Phoenix, AZ). BRAF mutations were detected by NGS and classified using published literature (Sahin et al. JCO OP 2021). Interferon gamma signature and MAPK pathway activity score (MPAS) were calculated using RNA expression data (TPM). Real-world overall survival information was obtained from insurance claims and calculated from tissue collection to last contact, while post-treatment survival from first of treatment to last contact. KM estimates were calculated for molecularly defined cohorts. Significance was determined as p values of ,0.05. Results: A total of 930,105, and 262 pts with class I, II, and III BRAF mts were identified. Pts with class III BRAF mts were significantly more common among younger pts (age,45) compared to class I and class II (8.8% vs. 4.8% vs. 1.0 % respectively; P,0.05). Class I BRAF mts were significantly enriched with consensus molecular subtype 1 (CMS1) (Class I, II and III: 44% vs. 17% vs. 18%) while class II and III BRAF mts were more often CMS2 subtype (canonical) compared to class I (2%, 30% and 35%, p,0.05). Class I BRAF and KRAS/NRAS mts were mutually exclusive, while KRAS mts incidences were 15% and 22% for class II and class III, and NRAS mts incidence and PIK3CA between EUR and the other ancestry groups in both MSI and MSS tumors (Table). Median exposure levels to alkylation were higher in EAS v EUR. Conclusions: These data were 8% and 12%, respectively. MPAS score was significantly lower for class III (-0.32, arbitrary unit) compared to Class I (p,0.05), but similar MPAS scores were seen in class I and confirm previous results in AFR populations, and reveal novel differences in the EAS and LAT II (1.3 versus 1.38). No difference in interferon gamma signature was noted between classes. populations. Findings from this study may provide information for developing risk stratifi-cation and prevention strategies for the early detection of cancer and provide rationale for precision treatment based on ancestry. Research Sponsor: None. MSI MSS AFR (n=193) EAS (n=185) LAT (n=147) EUR (n=1524) AFR (n=1504) EAS (n=2062) LAT (n=1144) EUR (n=9002) APC 61.7%** 55.5% 46.3% 47.0% 81.4%** 83.3%** 76.0% 75.2 BRAF 34.2%** 43.2%* 27.2%** 54.2% 4.7%** 4.8%** 4.8%* 7.6% KRAS 40.4%** 23.8% 36.7%** 21.7% 53.7%** 42.4% 44.4% 41.6% TP53 30.1% 37.3% 32.7% 30.0% 64.3%* 78.4%** 68.6% 67.9% PIK3CA 39.4% 36.2% 37.4% 37.3% 20.9%* 15.8% 17.7% 17.9% Pts with class II and III mts had significantly better overall survival compared to patients with class I mts (HR=0.69 CI: 0.597-0.804 p,0.0001) and slightly worse overall survival compared to wild-type BRAF pts. (HR; 0.85 CI: 0.74-0.96 P=0.011). Among pts treated with anti-EGFR, pts with class II and III BRAF mts had significantly better post-anti-EGFR survival compared to class I BRAF mts (HR 0.498 CI 0.32-0.766 P=0.001 and similar survival compared to those with BRAF wild-type (P=0.21). Conclusions: Class II and III BRAF mts are associated with improved outcomes with EGFR blockade and represent a distinct biological subgroup of pMMR CRC. Class III BRAF mts have lower MAPK activation, consistent with the pattern of kinase-dead mutations. Research Sponsor: None.|Victoria and Philip Wilson Research Fund, Fong research project and Ming Hsieh research fund. Recognition of neoantigens by autologous T cells promotes sensitivity to immune checkpoint inhibitors (ICI) in mismatch repair deficient (MMRd)/microsatellite instability high (MSI-H) tumors. Neoantigen-targeted reactivity has also been reported in microsatellite stable (MSS) tumors, and neoantigens are emerging targets for tumor vaccines and adoptive cell therapy. Here, we aimed to comprehensively assess the spectrum of immunogenic neoantigens in CRC to identify new subpopulations for these therapeutic strategies. Methods: 7,053 CRC tested at Caris Life Sciences (Phoenix, AZ) with NextGen Sequencing on DNA (720-gene panel) and RNA (whole transcriptome) were analyzed. MSI status was determined by immunohistochemistry of MMR proteins and/or NGS. Immune epitope prediction was performed on translated peptide sequences harboring detected mutations using the NetMHCpan v4.0 method in the Immune Epitope Database, with HLA genotyping performed using arcasHLA. Immune/stromal cell abundance in the tumor microenvironment (TME) was estimated from RNA expression profiles using MCP-Counter. Gene expression profiles were analyzed for a transcriptional signature predictive of response to immunotherapy (T cell-inflamed signature, TIS). Results: 6,600,005 unique peptide:allele interactions were tested, of which 368,468 (5.6%) were predicted neoantigens with patient-specific HLA alleles, including 16,184 (0.25%) with high affinity. MMRd/MSI-H tumors (6.9%) had higher neoantigen load at all affinity levels compared to MSS, with 10,243 (63.3%) and 5,621 (34.7%) of the predicted high affinity neoantigens exclusively associated with MSS and MMRd/MSI-H, respectively. 32 recurrent high affinity neoantigens were identified in . 10 samples, most frequently derived from APC mutations in MSS tumors invasion and lymph node metastases (more advanced T and N stage) are associated with increased risk of liver metastases, but how co-pathologies of the liver associate with disease progression and survival are not known. Further, prognostic factors associated with overall survival in patients with colorectal liver metastases (CRLM) remain poorly understood. Clinical factors affecting liver morphology and biomechanical properties, such as preexisting fibrosis or steatosis, may impact the pathogenesis of CRLM and thus the clinical prognosis. Current literature is mixed about whether prior steatosis and fibrosis contribute significantly to CRLM pathogenesis and prognosis. The purpose of this study is to evaluate whether liver steatosis and fibrosis impact outcomes in patients mutations leading to clonal expansion of hematopoietic stem cells and is a common incidental finding in circulating tumor DNA (ctDNA). Inflammation from these cells or a reduced marrow reserve may impact treatment outcomes or adverse events. We investigated the incidence of CHIP in ctDNA from patients with gastrointestinal (GI) cancers and explored its association with outcomes and adverse events (AEs). Methods: We collected ctDNA results from a local prospective metastatic colorectal cancer (mCRC) cohort (PREDICT-L) and ctDNA data from two randomized trials: CCTG CO.26 (durvalumab + tremelimumab [D+T] or best supportive care [BSC] in mCRC) and CCTG PA.7 (gem-citabine and nab-paclitaxel [GN] with or without D+T in metastatic pancreatic adenocarcinoma [mPDAC]). CHIP+ was defined as the presence of a variant of $2% variant allele frequency annotated in the ctDNA report in any of the genes DNMT3A, TET2, ASXL1 and ATM, and not annotated as germline by respective sequencing platforms. The first line of treatment after ctDNA was reviewed, and with CRLM. Methods: All CLRM cases (n = 197) that underwent resection between 2003 grade $3 or dose-limiting adverse events were documented. Results: The prevalence of CHIP varied and 2007 from The Cancer Imaging Archive were included in our study cohort. For each from 10% to 18% (see table). CHIP+ patients were older than CHIP-in the CO.26 cohort (p=0.011), and clinical covariate, we generated a univariate model for overall survival and those ECOG was higher in CHIP+ patients in the PREDICT-L cohort. There was no difference between CHIP+/-meeting a modest predictive threshold (p , 0.15) were included in a multivariable model. These included: presence of major comorbidity, chemotherapy preceding re-section of liver metastases, clinical risk score, presence of extrahepatic disease at time of diagnosis, presence of steatosis on CT imaging, percentage of residual tumor after treatment, and presence of fibrosis on CT. All statistics were performed in R (v.2022.12.0). Results: A multivariable Cox proportional hazards model identified four statistically significant clinical factors predictive of overall survival: clinical risk score patients with regards to sex. DNMT3A was the gene most frequently mutated in all three cohorts. There was no significant difference in PFS or OS between the CHIP+/-groups, both in those treated with chemotherapy (Chemo) or immunotherapy (IO). The most common AEs were rash, GI toxicities and bleeding/clotting abnormalities. There was no significant difference in the rates of AEs between the CHIP+/-groups for those treated with Chemo or IO. Conclusions: CHIP is a common alteration in ctDNA but did not impact PFS, OS, or the chance of developing an AE. Research Sponsor: AstraZeneca (sponsored the CO.26 and PA.7 clinical trials). (78% of recurrent neoantigens), and from RNF43 (25%), ASXL1 (20%), and KMT2D (15%) in MMRd/MSI-H. TIS scores positively correlated with the abundance of various immune cell populations in the TME, notably cytotoxic lymphocytes (r = 0.46). Among the recurrent high affinity neoantigens, those with the highest mean TIS scores (. 90 th percentile) resulted from mutation of MSH3 (K383fs, 5.1%) and KMT2D (multiple variants, 2.8%) in MMRd/MSI-H CRC, while those in MSS CRC derived from SOX9 (multiple variants, 0.2%) and APC (multiple variants, 0.7%) but were not associated with increased mean TIS scores (~55 th percentile). Conclusions: This is one of the largest studies to investigate the landscape of immunogenic neoantigens in CRC. We were able to identify candidate recurrent peptides with high HLA binding affinity and an association with a positive TIS signature supporting the role of neoantigens as potential cancer immunotherapy targets. Research Sponsor: Partly supported by National Cancer Institute (grant number P30CA014089), Gloria Borges WunderGlo Foundation, Dhont Family Foundation, Gene Gregg Pancreas Research Fund, San Pedro Peninsula Cancer Guild; Daniel Butler Research Fund, V foundation for cancer research, (HR = 1.60, p = 0.026), presence of extrahepatic disease (HR = 2.33, p = 0.027), presence of steatosis (HR = 0.51, p = 0.0057), and fibrotic proportion of liver tissue less than 40% CO.26 PA.7 PREDICT-L D+T vs BSC D+T + GN vs GN Physician choice (n= 169) (n=173) (n=41) Tumor type mCRC mPDAC mCRC (HR = 2.63, p = 0.033). There were also four statistically significant clinical factors Assay Used GuardantOMNI Predicine Atlas FoundationOne Liquid CDx predictive of disease-free survival in the liver: chemotherapy preceding resection of liver metastases (HR = 2.28, p = 0.0011), presence of extrahepatic disease (HR = 2.18, p = 0.024), presence of steatosis (HR = 0.49, p = 0.0030), and fibrotic proportion of liver Median Age years (interquartile range) 65 (58-72) 65 (58-70) 66 (61-72) CHIP Prevalence n (%) 30 (18) 18 (10) 7 (17) Hazard Ratio (HR) or Odds Ratio (OR) CHIP+ versus CHIP-[95% confidence interval] P-value tissue less than 40% (HR = 2.74, p = 0.016). Conclusions: Our findings suggest that increased steatosis and fibrosis, as assessed by CT scans, are paradoxically protective in CRLM, showing longer disease-free survival and overall survival rates. We hypothesize that liver fibrosis and steatosis impact the microenvironment of the neoplastic cells in the liver, impairing tumor progression in this milieu. Further research is needed to assess PFS HR Chemo 1.53 [0.76-3.10] p=0.23 0.60 [0.31-1.13] p=0.11 0.66 [0.13-3.28] p=0.62 IO +/-Chemo 0.98 [0.57-1.66] p=0.93 1.65 [0.57-4.75] p=0.35 N/A OS HR Chemo 1.15 [0.59-2.27] p=0.68 0.55 [0.17-1.78] p=0.32 N/A IO +/-Chemo 1.26 [0.73-2.16] p=0.41 0.76 [0.39-1.46] p=0.403 N/A AEs OR how non-neoplastic co-pathologies resulting in biophysical changes affect tumor growth Chemo N/A 1.44 [0.098-21.3] p=1 1.49 [0.20-17.92] p=1 and overall survival. Research Sponsor: None. IO +/-Chemo 0.92 [0.091-4.76] p=1 1.19 [0.33-4.31] p=0.78 N/A|Victoria and Philip Wilson Research Fund, Fong research project and Ming Hsieh research fund. Recognition of neoantigens by autologous T cells promotes sensitivity to immune checkpoint inhibitors (ICI) in mismatch repair deficient (MMRd)/microsatellite instability high (MSI-H) tumors. Neoantigen-targeted reactivity has also been reported in microsatellite stable (MSS) tumors, and neoantigens are emerging targets for tumor vaccines and adoptive cell therapy. Here, we aimed to comprehensively assess the spectrum of immunogenic neoantigens in CRC to identify new subpopulations for these therapeutic strategies. Methods: 7,053 CRC tested at Caris Life Sciences (Phoenix, AZ) with NextGen Sequencing on DNA (720-gene panel) and RNA (whole transcriptome) were analyzed. MSI status was determined by immunohistochemistry of MMR proteins and/or NGS. Immune epitope prediction was performed on translated peptide sequences harboring detected mutations using the NetMHCpan v4.0 method in the Immune Epitope Database, with HLA genotyping performed using arcasHLA. Immune/stromal cell abundance in the tumor microenvironment (TME) was estimated from RNA expression profiles using MCP-Counter. Gene expression profiles were analyzed for a transcriptional signature predictive of response to immunotherapy (T cell-inflamed signature, TIS). Results: 6,600,005 unique peptide:allele interactions were tested, of which 368,468 (5.6%) were predicted neoantigens with patient-specific HLA alleles, including 16,184 (0.25%) with high affinity. MMRd/MSI-H tumors (6.9%) had higher neoantigen load at all affinity levels compared to MSS, with 10,243 (63.3%) and 5,621 (34.7%) of the predicted high affinity neoantigens exclusively associated with MSS and MMRd/MSI-H, respectively. 32 recurrent high affinity neoantigens were identified in . 10 samples, most frequently derived from APC mutations in MSS tumors invasion and lymph node metastases (more advanced T and N stage) are associated with increased risk of liver metastases, but how co-pathologies of the liver associate with disease progression and survival are not known. Further, prognostic factors associated with overall survival in patients with colorectal liver metastases (CRLM) remain poorly understood. Clinical factors affecting liver morphology and biomechanical properties, such as preexisting fibrosis or steatosis, may impact the pathogenesis of CRLM and thus the clinical prognosis. Current literature is mixed about whether prior steatosis and fibrosis contribute significantly to CRLM pathogenesis and prognosis. The purpose of this study is to evaluate whether liver steatosis and fibrosis impact outcomes in patients mutations leading to clonal expansion of hematopoietic stem cells and is a common incidental finding in circulating tumor DNA (ctDNA). Inflammation from these cells or a reduced marrow reserve may impact treatment outcomes or adverse events. We investigated the incidence of CHIP in ctDNA from patients with gastrointestinal (GI) cancers and explored its association with outcomes and adverse events (AEs). Methods: We collected ctDNA results from a local prospective metastatic colorectal cancer (mCRC) cohort (PREDICT-L) and ctDNA data from two randomized trials: CCTG CO.26 (durvalumab + tremelimumab [D+T] or best supportive care [BSC] in mCRC) and CCTG PA.7 (gem-citabine and nab-paclitaxel [GN] with or without D+T in metastatic pancreatic adenocarcinoma [mPDAC]). CHIP+ was defined as the presence of a variant of $2% variant allele frequency annotated in the ctDNA report in any of the genes DNMT3A, TET2, ASXL1 and ATM, and not annotated as germline by respective sequencing platforms. The first line of treatment after ctDNA was reviewed, and with CRLM. Methods: All CLRM cases (n = 197) that underwent resection between 2003 grade $3 or dose-limiting adverse events were documented. Results: The prevalence of CHIP varied and 2007 from The Cancer Imaging Archive were included in our study cohort. For each from 10% to 18% (see table). CHIP+ patients were older than CHIP-in the CO.26 cohort (p=0.011), and clinical covariate, we generated a univariate model for overall survival and those ECOG was higher in CHIP+ patients in the PREDICT-L cohort. There was no difference between CHIP+/-meeting a modest predictive threshold (p , 0.15) were included in a multivariable model. These included: presence of major comorbidity, chemotherapy preceding re-section of liver metastases, clinical risk score, presence of extrahepatic disease at time of diagnosis, presence of steatosis on CT imaging, percentage of residual tumor after treatment, and presence of fibrosis on CT. All statistics were performed in R (v.2022.12.0). Results: A multivariable Cox proportional hazards model identified four statistically significant clinical factors predictive of overall survival: clinical risk score patients with regards to sex. DNMT3A was the gene most frequently mutated in all three cohorts. There was no significant difference in PFS or OS between the CHIP+/-groups, both in those treated with chemotherapy (Chemo) or immunotherapy (IO). The most common AEs were rash, GI toxicities and bleeding/clotting abnormalities. There was no significant difference in the rates of AEs between the CHIP+/-groups for those treated with Chemo or IO. Conclusions: CHIP is a common alteration in ctDNA but did not impact PFS, OS, or the chance of developing an AE. Research Sponsor: AstraZeneca (sponsored the CO.26 and PA.7 clinical trials). (78% of recurrent neoantigens), and from RNF43 (25%), ASXL1 (20%), and KMT2D (15%) in MMRd/MSI-H. TIS scores positively correlated with the abundance of various immune cell populations in the TME, notably cytotoxic lymphocytes (r = 0.46). Among the recurrent high affinity neoantigens, those with the highest mean TIS scores (. 90 th percentile) resulted from mutation of MSH3 (K383fs, 5.1%) and KMT2D (multiple variants, 2.8%) in MMRd/MSI-H CRC, while those in MSS CRC derived from SOX9 (multiple variants, 0.2%) and APC (multiple variants, 0.7%) but were not associated with increased mean TIS scores (~55 th percentile). Conclusions: This is one of the largest studies to investigate the landscape of immunogenic neoantigens in CRC. We were able to identify candidate recurrent peptides with high HLA binding affinity and an association with a positive TIS signature supporting the role of neoantigens as potential cancer immunotherapy targets. Research Sponsor: Partly supported by National Cancer Institute (grant number P30CA014089), Gloria Borges WunderGlo Foundation, Dhont Family Foundation, Gene Gregg Pancreas Research Fund, San Pedro Peninsula Cancer Guild; Daniel Butler Research Fund, V foundation for cancer research, (HR = 1.60, p = 0.026), presence of extrahepatic disease (HR = 2.33, p = 0.027), presence of steatosis (HR = 0.51, p = 0.0057), and fibrotic proportion of liver tissue less than 40% CO.26 PA.7 PREDICT-L D+T vs BSC D+T + GN vs GN Physician choice (n= 169) (n=173) (n=41) Tumor type mCRC mPDAC mCRC (HR = 2.63, p = 0.033). There were also four statistically significant clinical factors Assay Used GuardantOMNI Predicine Atlas FoundationOne Liquid CDx predictive of disease-free survival in the liver: chemotherapy preceding resection of liver metastases (HR = 2.28, p = 0.0011), presence of extrahepatic disease (HR = 2.18, p = 0.024), presence of steatosis (HR = 0.49, p = 0.0030), and fibrotic proportion of liver Median Age years (interquartile range) 65 (58-72) 65 (58-70) 66 (61-72) CHIP Prevalence n (%) 30 (18) 18 (10) 7 (17) Hazard Ratio (HR) or Odds Ratio (OR) CHIP+ versus CHIP-[95% confidence interval] P-value tissue less than 40% (HR = 2.74, p = 0.016). Conclusions: Our findings suggest that increased steatosis and fibrosis, as assessed by CT scans, are paradoxically protective in CRLM, showing longer disease-free survival and overall survival rates. We hypothesize that liver fibrosis and steatosis impact the microenvironment of the neoplastic cells in the liver, impairing tumor progression in this milieu. Further research is needed to assess PFS HR Chemo 1.53 [0.76-3.10] p=0.23 0.60 [0.31-1.13] p=0.11 0.66 [0.13-3.28] p=0.62 IO +/-Chemo 0.98 [0.57-1.66] p=0.93 1.65 [0.57-4.75] p=0.35 N/A OS HR Chemo 1.15 [0.59-2.27] p=0.68 0.55 [0.17-1.78] p=0.32 N/A IO +/-Chemo 1.26 [0.73-2.16] p=0.41 0.76 [0.39-1.46] p=0.403 N/A AEs OR how non-neoplastic co-pathologies resulting in biophysical changes affect tumor growth Chemo N/A 1.44 [0.098-21.3] p=1 1.49 [0.20-17.92] p=1 and overall survival. Research Sponsor: None. IO +/-Chemo 0.92 [0.091-4.76] p=1 1.19 [0.33-4.31] p=0.78 N/A||

|162 166 170|Poster Session Poster Session Poster Session|163 167|Poster Session Poster Session|

|Development of an improved risk stratification scheme for stage II and III Real-world evaluation of clinical outcomes and long-term survivors in pa-Association of candidate alterations with primary resistance to KRAS G12D|Real-world biomarker testing patterns among patients with metastatic co-The prognostic significance of extramural venous invasion detected via|Real-world biomarker testing patterns among patients with metastatic co-The prognostic significance of extramural venous invasion detected via||

|colorectal cancers through incorporation of the digital pathology biomarker tients with BRAF-V600E metastatic colorectal cancer. First Author: William targeting in colorectal cancer. First Author: Khalid Jazieh, Mayo Clinic, Rochester,|lorectal cancer (mCRC) treated with later lines of therapy (LOT) in the United contrast-enhanced computed tomography colonography in colon cancer.|lorectal cancer (mCRC) treated with later lines of therapy (LOT) in the United contrast-enhanced computed tomography colonography in colon cancer.||

|QuantCRC. First Author: Rish Pai, Department of Pathology and Laboratory Medicine, Phillips, University of Ottawa, Ottawa, ON, Canada MN|States (US) community oncology setting. First Author: Arvind Katta, Bayer First Author: Takeharu Kato, Department of Colorectal Surgery, National Cancer Center|States (US) community oncology setting. First Author: Arvind Katta, Bayer First Author: Takeharu Kato, Department of Colorectal Surgery, National Cancer Center||

|Mayo Clinic Arizona, Phoenix, AZ Background: There is a need to improve current risk stratification of stage II and III colorectal cancer (CRC) to better inform risk of recurrence and guide adjuvant che-motherapy. The purpose of this study is to examine whether integration of QuantCRC, an AI-based digital pathology biomarker utilizing hematoxylin and eosin-stained slides, provides improved risk stratification over current American Society of Clinical Oncology (ASCO) guidelines. Methods: ASCO and QuantCRC-integrated risk schemes were ap-plied to an observational cohort of 1,068 stage II and III CRCs. The stage II integrated scheme utilizes pT3 vs. pT4 and QuantCRC-derived risk groups. The stage III integrated scheme utilizes pT1-3 vs. pT4, pN1 vs. pN2, and QuantCRC-derived risk groups. Per-formance metrics included log-rank test, hazard ratios and Somers' Dxy rank correlation. Results: Integration of QuantCRC provides improved risk stratification compared to the ASCO scheme for stage II and III CRC. The QuantCRC-integrated scheme placed more stage II tumors in the low-risk group compared to the ASCO scheme (69.3% vs. 60.4%) without decreased 3-year RFS. The QuantCRC-integrated scheme provided larger hazard ratios (HR) for both intermediate-risk (3.04, 95%CI 1.81-5.10, P=2.8x10 -5 ) and high-risk (4.62, 95%CI 2.02-10.61, P=0.0003) groups compared to ASCO intermediate-risk (2.09, 95%CI 1.21-3.63, P=0.008) and high-risk (3.08, 95%CI 1.57-6.01, P=0.001) groups. The QuantCRC-integrated scheme for stage III tumors identified a small group of 80/518 (15.4%) CRCs at very high risk of recurrence with HR of 4.08 (95%CI 2.68-6.23, P=6.5x10 -11 ) compared to a HR of 2.42 (95%CI 1.72-3.38, P=3.1x10 -7 ) for 228/518 (44.0%) high-risk CRCs in the ASCO scheme. QuantCRC-integrated risk groups remained prognostic in stage III CRCs when stratified by presence or absence of any adjuvant chemotherapy. No difference in RFS were seen in QuantCRC-integrated low-risk and intermediate-risk stage III CRCs stratified by 3 vs. 6-months of oxaliplatin-based adjuvant chemotherapy suggesting that these two groups can be treated with 3-months of adjuvant therapy. Conclusions: Incorporation of QuantCRC into risk stratification provides a powerful predictor of RFS that has potential to guide subsequent treatment and surveillance. Background: KRAS-mutant colorectal cancer (CRC) has a worse prognosis and greater resistance to Background: BRAF-V600E mutant metastatic colorectal cancer (BRAF-V600E mCRC) is therapy, attracting tremendous efforts to develop both allele-specific and pan-KRAS targeting agents associated with poor prognosis but confers response to combination BRAF/EGFR including KRAS G12C and G12D inhibitors. CRC has demonstrated both primary and acquired re-blockade. The goal of this study is to evaluate the clinicopathologic features and sistance to KRAS G12C inhibitors, which can be better evaluated by circulating tumor DNA (ctDNA)-natural history of BRAF-V600E mCRC in the era prior to combination BRAF/EGFR in-based next generation sequencing (NGS) methods without tissue sampling bias. Here, we utilized hibitors. Methods: This is a retrospective study of patients treated at the Ottawa Hospital Cancer Centre with BRAF-V600E mCRC who did not receive combination BRAF/ EGFR therapy. Patients diagnosed with colorectal cancer prior to March 31, 2021, were included. Demographic, clinical, pathologic and cancer characteristics were abstracted from electronic medical records. Outcomes of interest included duration of therapy, as a surrogate of progression free survival, and overall survival (OS). Long-term survivor was defined as OS greater than 2 years. Results: 74 patients were included. Median age was 70 years (IQR=61-78), and 39 (53%) patients were female. There were 17 (23%) patients clinical ctDNA data to delineate the landscape of candidate alterations associated with primary resistance to KRAS G12D targeting in CRC. Methods: Samples from advanced CRC patients with Guardant360 data in 2021 were categorized into a KRAS G12D group and comparator groups of KRAS G12C and KRAS not detected (ND) according to KRAS mutation status. Demographics, MSI-H status, and blood tumor mutational burden (bTMB) were summarized and compared between groups using t-test for continuous variables and Fisher's exact test for categorical variables. Co-occurrence patterns of alterations between KRAS and other genes were assessed. Primary resistance mutations were inferred by acquired resistance findings to KRAS G12C inhibitors reported by Awad et al. N Engl J Med. 2021 and Tanaka et al. Cancer Discov. 2021. Results: Among approximately 2500 samples, 16.8% had alive at the end of the follow-up period. 31 (42%) patients had poorly differentiated grade KRAS G12D, the most common KRAS mutation in CRC. The mean allele frequency of KRAS G12D and 26 (35%) were mismatch repair deficient (dMMR). Locations of metastases included (11.4%) is comparable to that of KRAS G12C (10.9%). Mean age (61.6 years), MSI-H frequency (3.8%), liver (40, 54%), peritoneum (30, 41%), lung (18, 24%), bone (5, 7%) and brain (5, 7%). and mean bTMB (14.2 Mut/Mb) of KRAS G12D group is comparable to those of KRAS ND group. This contrasts with KRAS G12C with significantly lower mean age (60.2 years, p=0.01), lower MSI-H Overall, 64 (86%) patients received first line systemic therapy, 19 (26%) second line, and frequency (0.56%, p=0.03), and higher mean bTMB (16.3 Mut/Mb, p=0.02) compared to KRAS ND. Both 5 (7%) third line (see Table). Median duration of therapy in the first line was 4.3 months (IQR=2.0-9.6), second line was 2.9 months (IQR=1.4-4.1), and third line 1.0 months KRAS G12D and G12C significantly co-occur with APC, PIK3CA, and SMAD4 alterations. FBXW7, AR, and KEAP1 alterations were unique co-occurrences to KRAS G12D, while KIT was unique to KRAS (IQR=1.0-1.9). Overall survival in the entire cohort was 13.2 months (IQR=4.6-25.4). Importantly, 21 (28%) patients were long-term survivors, of which 8 (11%) were dMMR. Conclusions: Patients with BRAF-V600E mCRC generally have poor clinical outcomes G12C. Candidate alterations associated with primary resistance in KRAS G12D CRC included si-multaneously present mutations of KRAS Q61H (14.1%), G12V (6.4%), G12C (5.9%), G13D (3.6%), BRAF V600E (2.7%) and others, amplification of MET (2%), MYC (1.6%), and KRAS (1.4%), and FGFR3-with traditional systemic therapies. In this study, we identified approximately 25% of patients who are long-term survivors (OS .2 years). This reflects the real-world het-TACC3 translocation (Table). Conclusions: KRAS G12D is associated with unique co-occurring molecular alterations compared to KRAS G12C in CRC. ctDNA-based NGS platforms can survey candidate alterations associated with primary resistance to KRAS G12D targeting in CRC. Further erogeneity of clinical outcomes for patients with BRAF-V600E mCRC who did not receive BRAF/EGFR targeted therapy. Research Sponsor: None. validation in preclinical models is needed. Research Sponsor: None. Gene Alteration Frequency Gene Alteration Frequency Summary of systemic therapy received in the overall cohort by line of treatment. Treatment First Line, n=64 Second Line, n=19 Third Line, n=5 Combination Chemotherapy* 47 (73%) 11 (58%) 1 (20%) KRAS Q61H 14.1% MAP2K1 K57N 1.6% KRAS G12V 6.4% MYC AMP 1.6% KRAS G12C 5.9% KRAS AMP 1.4% Research Sponsor: None. Singlet chemotherapy 10 (16%) 3 (16%) 1 (20%) Biologic** 26 (41%) 3 (16%) 1 (20%) Pembrolizumab 4 (6%) 4 (21%) 0 (0%) *FOLFOX, FOLFIRI, CAPOX, or CAPIRI. **Cetuximab, panitumumab or bevacizumab +/-che-motherapy backbone. PIK3CA H1047R 5.0% MAP2K1 Q56P 1.1% KRAS G13D 3.6% KRAS G12R 0.9% BRAF V600E 2.7% KRAS Y96D 0.5% NRAS Q61K 2.7% MAP2K1 E102_I103del 0.5% MET AMP 2.0% PTEN G209V 0.2% NRAS Q61R/L 4.0% FGFR3-TACC3 0.2%|). Conclusions: Integrating histopathological, clinicogenomic, and tumoroid response data, this expanding online resource provides a platform to identify valid biomarkers for patient treatment response. This publicly available biorepository built within cBioPortal is intuitive and flexible to accommodate and organize a wide range of data and has the potential to serve as an important resource in rectal cancer research. Research Sponsor: National Institute of Health: National Cancer Institute. Healthcare Pharmaceuticals, Whippany, NJ Background: Testing for BRAF and KRAS/NRAS mutations, HER2 amplifications, and MSI/ MMR status is a standard of care for all patients with mCRC. There are limited real-world (RW) data regarding biomarker testing patterns among robust patients who are candidates for multiple LOT. We evaluated biomarker testing patterns among patients treated in community oncology practices who initiated regorafenib (REGO) and/or trifluridine/ tipiracil (FTD/TPI), predominantly in 3 rd or later lines of therapy. Methods: A retro-spective analysis utilizing electronic medical record data from The US Oncology Network examined adult patients with mCRC who initiated REGO and/or FTD/TPI between 09/01/ 2015 and 11/30/2022 with follow-up until 05/31/2023. The proportion of patients tested for various biomarkers was assessed. Results: A total of 2684 mCRC patients initiated REGO and/or FTD/TPI (including 895 pts receiving both) in any LOT during the study period. The mean age of patients at baseline was 62.9 years, of whom 54.9% were male, 1599 (59.6%) patients were White and 436 (16.2%) were underrepresented minorities (Black or Hospital, Chuo-Ku, Tokyo, Japan Background: The precise effects of extramural venous invasion (EMVI) and Spiculation on colon cancer recurrence remain poorly understood. This study investigated the clinical significance of ctEMVI and ctSpiculation as diagnosed via preoperative contrast-enhanced CT colonography (CTC) using three-dimensional multiplanar reconstruction (3D MPR) images. Methods: Patients with stage I-Ⅲ colon can-cer (T2 or deeper) diagnosed via CTC at the National Cancer Center Hospital in Japan between 2013 and 2018 were retrospectively evaluated for ctEMVI and ctSpiculation, diagnosed by two observers using 3D MPR images of slices 0.5 mm thick. The interobserver reliability was assessed with Cohen's kappa statistic, and recurrence-free survival (RFS) was analyzed using Kaplan-Meier curves. Preoperative clinical factors were subjected to Cox regression analysis in relation to RFS. Results: Of 922 patients, 544 eligible cases were analyzed. There were 50 (9.2%) ctEMVI-positive cases and 494 (90.8%) ctEMVI-negative cases, along with 186 (34.2%) ctSpiculation-positive cases and 358 (65.8%) with negative findings. Kappa coefficients for ctEMVI and ctSpiculation were 0.830 and 0.718, respectively. Kaplan-Meier analysis and log-rank tests demonstrated lower RFS in ctEMVI-and ctSpiculation-positive cases (p,0.001). In multivariable analysis, ctT4 (HR 2.95, 95% CI 1.73-5.02) and ctEMVI (2.97, 1.81-4.87) were independent factors associated with RFS. When stratifying TNM stages based on ctEMVI status, in N(+) (i.e., Stage III), ctEMVI-positive group had worse prognoses than negative group (5-year RFS rates; 52.0% vs. 78.5%, p=0.003). Similarly, in N(-) (i.e., Stage I and II), Hispanic/Latino). Patients were most commonly tested for KRAS mutations (75.2%) and T3N0EMVI(+) cases had significantly worse prognoses than T3N0EMVI(-) and Stage I cases (50.6% vs. 89.3% least commonly for HER2 amplifications (22.6%). Age, gender, and race/ethnicity char-acteristics were similar between treatment subgroups, with 29.6% of minority and 23.1% of white patients not undergoing KRAS testing. Types of biomarkers tested and proportion of patients tested are reported in the table below. Conclusions: About one quarter of patients who were sufficiently robust to receive aggressive therapy did not undergo testing for KRAS, the oldest standard of care biomarker in CRC. We observed disparities by race/ and 90.1%) and were comparable to the T4N0 group (50.6% vs. 46.7%, p=0.844). Conclusions: Both ctEMVI and ctSpiculation are associated with RFS. ctEMVI is an independent predictor of recurrence and may be valuable in combination with preoperative TNM staging to identify patients at high risk for recurrence. Research Sponsor: None. Univariable analysis Multivariable analysis Variable Group HR 95% CI P HR 95% CI P ethnicity. We also observed a correlation between rates of testing and treatment intensity, with patients who received both REGO and FTD/TPI having a higher rate of testing than those who received only one of the treatments. Understanding the pitfalls in biomarker testing will help pave the way for appropriate and equitable access to cancer care. Sex Female Ref Male 1.10 0.74-1.64 0.636 1.05 0.80-1.59 0.799 Age (years) 1.65 1.11-2.45 0.014 1.29 0.84-1.97 0.240 #65 .65 Ref BMI (kg/m 2 ) #25 Ref .25 1.32 0.83-2.09 0.236 1.29 0.80-2.08 0.294 Research Sponsor: Bayer AG. Percentage of patients with documented biomarker testing. Biomarker Overall (N=2684) Minority (N=436) White (N=1599) REGO or FTD/TPI (N=1789) Both REGO and FTD/TPI (N=895) CEA (ng/mL) #5 Ref .5 2.20 1.47-3.30 ,0.001 1.52 0.98-2.33 0.061 Tumor location Right Colon Ref Left Colon 1.21 0.79-1.83 0.380 1.00 0.64-1.56 0.997 ctT stage T2/T3 Ref T4 4.58 2.86-7.32 ,0.001 2.95 1.73-5.02 ,0.001 BRAF, N(%) 1314 (49.0%) 196 (45.0%) 798 (49.9%) 852 (47.6%) 462 (51.6%) KRAS, N(%) 2019 (75.2%) 307 (70.4%) 1230 (76.9%) 1328 (74.2%) 691 (77.2%) NRAS, N(%) 1059 (39.5%) 171 (39.2%) 614 (38.4%) 679 (38.0%) 380 (42.5%) HER2, N(%) 607 (22.6%) 92 (21.1%) 358 (22.4%) 388 (21.7%) 219 (24.5%) MSI/MMR, N(%) 1759 (65.5%) 279 (64.0%) 1045 (65.4%) 1160 (64.8%) 599 (66.9%) No 1.22 0.81-1.84 0.342 1.14 0.70-1.84 0.600 ctN stage Negative Ref Positive 1.98 1.33-2.95 ,0.001 1.27 0.77-2.08 0.351 ctEMVI Negative Ref Positive 4.25 2.68-6.75 ,0.001 2.97 1.81-4.87 ,0.001 ctSpiculation Negative Ref Positive 1.99 1.34-2.96 1.18 0.76-1.85 0.460 ,0.001 Adjuvant chemotherapy Yes Ref|||

|48s|COLORECTAL CANCER||| |---|---|---|---|

|||189 193 197|Poster Session Poster Session Poster Session|

|Myostatin/activin pathway gene expression and single nucleotide polymor-Incidence and genomic characteristics of gene fusions in a large Chinese Redefining the prognostic significance of RAS and BRAF V600E mutations Utilizing quantitative pathologic analysis of digitized images of rectal can-|The landscape of the comprehensive genomic profile for patients with bowel Impact of acquired RAS, BRAF and PIK3CA mutation at 8 weeks on the RAS mutation specific survival in patients with metastatic colorectal cancer|The landscape of the comprehensive genomic profile for patients with bowel Impact of acquired RAS, BRAF and PIK3CA mutation at 8 weeks on the RAS mutation specific survival in patients with metastatic colorectal cancer||

|phisms (SNPs) in metastatic colorectal cancer (mCRC). First Author: Karam colorectal cancer cohort. First Author: Furong Kou, Key Laboratory of Carcino-on disease free survival in patients with colorectal cancer in the era of ct-cer (RC) to predict response to neoadjuvant therapy (NAT). First Author: Daniel|cancer. First Author: Tatsuro Yamaguchi, Department of Clinical Genetics, Tokyo efficacy of anti-EGFR monoclonal antibodies in metastatic colorectal treated with trifluridine/tipiracil. First Author: Peter Grell, Masaryk Memorial Cancer|cancer. First Author: Tatsuro Yamaguchi, Department of Clinical Genetics, Tokyo efficacy of anti-EGFR monoclonal antibodies in metastatic colorectal treated with trifluridine/tipiracil. First Author: Peter Grell, Masaryk Memorial Cancer||

|Ashouri, Norris Comprehensive Cancer Center, Keck School of Medicine, University of genesis and Translational Research (Ministry of Education), Department of Compre-DNA defined minimal residual disease: Results from the MD Anderson Walden, Department of Hematology/Oncology, Mayo Clinic Arizona, Phoenix, AZ|Metroplitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo-Ku, cancer. First Author: Takeshi Yamada, Department of Gastrointestinal and Hepato-Institute, Brno, Czech Republic|Metroplitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo-Ku, cancer. First Author: Takeshi Yamada, Department of Gastrointestinal and Hepato-Institute, Brno, Czech Republic||

|187 Japan Background: The aim of study was to clarify the landscape of comprehensive genomic Poster Session profile in bowel cancer. Methods: This study included 57,103 patients between June 1, 2019 and August 18, 2023 (version 20230821) with a nationwide retrospective design. Patients underwent one of three CGP tests, including OncoGuide, FoundationOne CDx (F1CDx), and FoundationOne Liquid (F1LCDx) CDx, at the physician's choice. We evaluated the pathogenicity of the detected variants based on the public database and gene function. Results: Of the 57,103 patients, 9,595 (16.8%) were bowel cancer, in-cluding 911 for OncoGuide, 7,711 for F1CDx and 810 for F1LCDx. In the tumor site, COADREAD was the most common bowel tumor, followed by SBC and APAD. TP53 was the most common gene with SNV/Indels, followed by APC, TP53, KRAS and PIK3CA. FLT3 was the most frequently amplified gene, followed by CDK8 and FLT1. For gene deletions, SMAD4 was the most frequently deleted gene, followed by PTEN and CDKN2A. For genomic rearrangements, EML4-ALK was the most common. A total of 46 (5.0%) 191 Poster Session presented in 2025. Clinical trial information: jRCT1050210160. Research Sponsor: Sysmex Corporation. Baseline ctDNA(N=40) ctDNA at 8 weeks (N=39) Wild (34) Mutant (6) P value Wild (34) Mutant (5) P value Liver metastases (yes) 23 (67.6%) 4 (66.7%) 1.00 23 (67.6%) 3 (60%) 1.00 Tumor sidedness (Left) 31(91.2%) 5 (81.3%) 0.49 32 (94.1%) 1 (80.0%) 0.35 Early tumor shrinkage (yes) 28(82.4%) 5 (83.3%) 1.00 28 (82.4%) 5 (100%) 0.57 Depth of response -33.4% (-82.9 to 48.0) -41.5% (-58 to 7.1) 0.41 -33.4% (-82.9 to 48.0) -48.5% (-64.1 to -40.9) 0.048 Skin rash ‡ G2 6 (17.4%) 0 (0%) 0.57 4 (11.7%) 2(40%) 0.167 195 Poster Session negative predictive value of KRAS G12 mutation in patients treated with T/T, however, OS depends on the specific G12 mutation. In contrast, patients with KRAS G13 mutation had worse survival. Research Sponsor: None. 199 Poster Session germline pathogenic variants were identified in OncoGuide in mismatch repair genes in Poster Session Background: Cancer cachexia leads to reduced overall survival (OS) in mCRC. Novel thera-Southern California, Los Angeles, CA peutics targeting the myostatin/activin pathway can reverse cachexia. Here we investigate the effect of myostatin/activin pathway gene expression and SNPs in mCRC patients (pts). Methods: Blood samples from 836 pts enrolled in 3 randomized first-line trials: TRIBE (FOLFIRI bevacizumab [bev] ; FOLFOXIRI bev), FIRE-3 (FOLFIRI bev; FOLFIRI cetuximab [cet]) and MAVERICC (FOLFIRI bev; FOLFOX bev) were genotyped by Illumina OncoArray. The impact on outcome of 13 SNPs from 5 myostatin/activin genes (ACVR1B, ACVR2A, ACVR2B, MSTN, INHBA) was tested. Gene expression analysis included 433 mCRC pts treated with either bev (n = 226) or cet (n = 207) in combination with first-line chemotherapy from the CALGB/SWOG 80405 trial (NCT00265850). RNA isolated from FFPE tumor samples were sequenced with HiSeq 2500 (Illumina). OS and progression-free survival (PFS) were compared by gene expression tertiles: low (L), medium (M), and high (H). Logrank test was used for univariate (UV) analysis, Cox proportional hazards regression for multivariate (MV). Results: Pts with the germline G/G variant of ACVR2B rs2276541 had worse PFS (FIRE-3 bev: 9.7 vs 12.2 months [mo] ; UV P = .044, MV P = .027; HR 2.10, 95%CI 1.13 -3.38 & FIRE-3 cet: 7.6 vs 13.2 mo; UV P = .047; HR 1.65, 95% CI 1.00 -2.72) and tumor response (TRIBE FOLFIRI bev: 48 vs 61%, MV P = .035) compared to any A carriers. Rs3749387 C/C variant in the same gene showed longer OS (MAVERICC FOLFOX bev: 36.9 vs 24.3 mo; MV P = .005; HR = 0.41, 95%CI 0.21-0.80) and PFS (MAVERICC FOLFIRI bev: 14.5 vs 11.8 mo; MV P = .009; HR = 0.53, 95%CI 0.32-0.88) relative to G variants. Any C allele in ACVR2A rs10497025 demonstrated improved OS (MAVERICC FOLFOX bev: 25.5 vs 11.9 mo; HR = 2.38, UV P = .035; 95%CI 1.03-5.50 & TRIBE FOLFIRI bev: 26.9 vs 22.4 mo; UV P = .017; HR = 1.90, 95%CI 1.11-3.26) and PFS (FIRE-3 -FOLFIRI cet : 32.1 vs 12.2 mo; UV P = .047; HR = 0.47, 95%CI 0.22-1.02 & MAVERICC FOLFOX bev 11.0 vs 6.8 mo; UV P = .006; HR = 2.52, 95%CI 1.26-5.00) relative to G/G. Tumor ACVR1B-H expression was associated with longer PFS (L/M/H, 9.5 vs 10.9 vs 13.5 mo, UV P = .034) and OS (L/M/H, 25.0 vs 28.2 vs 38.6 mo, UV P , .001) in all treated pts. ACVR1B-H also conferred improved OS in treatment subgroups (L/M/H; cet: 21.0 vs 27.4 vs 40.3 mo, UV P , .001; bev: 25.9 vs 29.0 vs 36.9 mo, UV P = .025). ACVR2B-L correlated with worse PFS (L/M/H, 10.3 vs 12.2 vs 11.2 mo, UV P = .043) and OS (L/M/H, 24.7 vs 33.8 vs 34.9 mo; P = .006) in the overall cohort. This association held true in cet treated patients (OS 21.2 vs 35.8 vs 37.1 mo; UV P , .001) but not bev. Conclusions: Our results suggest a role of cachexia SNPs and gene expression as a prognostic marker for mCRC undergoing first line treatment. These biomarkers may enable targeted treatments for cancer cachexia and support exploring this approach in combination with standard therapy in selected pts. Research Sponsor: U10CA180821, U10CA180882; https://acknowledgments.alliancefound.org. P30CA014089, UG1CA180830 [HJL]; UG1CA180830 and U10CA180888 (SWOG); Genentech. 0.001). Moreover, 404 (7.3%) patients had RNF43 splice or truncating mutations, and gene fusions were detected in 12.9% of these patients. Combining these markers in-creased the detection rate of fusions, with 28% (33/118) of the RAS/BRAF wildtype and MSI-H patients having fusions detected. Furthermore, in patients with wildtype RAS/ BRAF and MSI-H and RNF43 splice or truncating mutations, the fusion detection rate was as high as 49% (32/65), including 24 patients with actionable fusions of definite clinical significance. Conclusions: Gene fusions were detected in 4.4% of the Chinese CRC population and tended to occur in patients with wildtype RAS/BRAF, MSI-H, or RNF43 mutations. Combining the mutational status of RAS, BRAF, and RNF43 along with MSI status can improve the fusion detection rate and help select candidates for fusion testing and targeted therapy. Research Sponsor: None. 194 Poster Session radiographically evident disease at or shortly after the finding of ctDNA+. In a multi-variate model, after controlling for ctDNA status, there was no prognostic impact of RAS on DFS in the larger population with HR 1.51 (95% CI 0.88 -2.60; p = NS). While the number of pts with BRAF V600E mt was low, there was no evidence of a prognostic effect after controlling for ctDNA status. Conclusions: In CRC pts treated with curative intent, positive ctDNA at any point post-operatively or during surveillance is highly predictive of disease recurrence. In these pts, RAS mt status was not associated with DFS. Moreover, RAS mt pts are not more likely to be ctDNA+ve. Thus, our data suggest that the presence of ctDNA defined MRD has greater prognostic value than the presence or absence of RAS or BRAF V600E mt. Research Sponsor: None. 198 Poster Session hensive Clinical Trial Ward, Peking University Cancer Hospital & Institute, Beijing, China Background: Gene fusion is rare in colorectal cancer (CRC). With the advent of fusion-targeted therapeutics, such as entrectinib for NTRK fusion and selpercatinib for RET fusion, the identification of gene fusions holds clinical significance. Reports providing a comprehensive description of fusions in CRC are limited, and understanding the mo-lecular characteristics of CRC with fusions will contribute to efficient fusion screening. Here, we investigate the incidence and genomic features of gene fusions in a large Chinese CRC population. Methods: We systematically analyzed next-generation se-quencing results of tumor tissue from 5534 CRC patients between January 2020 and August 2023. The sequencing panel covers 769 cancer-related genes and can detect fusions, single nucleotide variants and indels, and microsatellite instability (MSI). Statistical significance was determined using chi-square test. Results: Overall, the median age of patients was 62 years (inter-quartile range [IQR]: 53-70), and 40% were female. Gene fusions were detected in 4.4% (242/5534) of all the patients. The incidence is 0.98% (54/5534) if only reported clinically actionable fusions are considered. The median age of the 242 fusion-positive patients was 64 years (IQR: 54-70), and 43% were female. The most highly detected potentially actionable gene fusions were NTRK (0.89%) and FGFR (0.81%), accounting for 39% of the fusion-positive patients. The other fusion genes were ERBB2 (0.52%), RET (0.38%), BRAF (0.31%), EGFR (0.27%), ALK (0.22%), MET (0.09%) and ROS1 (0.07%). Consistent with previous reports, patients with MSI-High were more likely to have fusions compared with those with microsatellite stability (MSS) or MSI-Low (9.9% vs 4.0%, p , 0.001). Besides, RAS or BRAF mutated patients accounted for 59% of the cohort, of whom 2.5% (83/3273) had fusions detected, while 7.0% (159/2261) of the RAS and BRAF wildtype patients had positive fusions (p , Billiary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan Background: Recent studies indicate that the emergence of RAS/BRAF mutation some-times occurs during initial anti-EGFR monoclonal antibody (mAb)-based treatment in metastatic colorectal cancer (mCRC). However, limited data was available regarding the timing and frequency of the emergence of RAS/BRAF mutation, and its impact on the efficacy of anti-EGFR mAb. With this background, we conducted an observational study to monitor RAS, BRAF, and PIK3CA mutation status by ctDNA in RAS/BRAF wt mCRC. INTERCEPT Program. First Author: Andrew Jared Pellatt, MD Anderson Hematol-Background: Trifluridine/tipiracil (T/T) is effective in patients with pretreated meta-Background: We developed and validated a quantitati ve segmentation algorithm (QuantCRC) to ogy/Oncology Fellowship, Houston, TX Background: In patients (pts) with resected colorectal cancer (CRC), circulating tumor DNA (ctDNA) is an emerging tool for the detection of minimal residual disease (MRD) following the completion of curative intent therapy. The presence of MRD is highly prognostic, with MRD+ pts having worse disease-free survival (DFS). Prior to the advent of ctDNA, the modest negative prognostic implications of BRAF and RAS mutations (mt) predict disease recurrence in stage I-III colorectal cancer patients (pts) based on the analysis of static colorectal cancer (mCRC). RAS mutational status could predict magnitude of T/T digitized hematoxylin and eosin (H+E) stained pathology slides. In this study, we aim to determine if effect (van de Haar et al, Nat Med. 2023), but the data are conflicting. Methods: We QuantCRC analysis on pre-treated RC biopsies can predict pathological complete response (pCR) retrospectively reviewed the clinical data of 402 patients consecutively treated with T/T after NAT which include total neoadjuvant therapy (TNT), chemoradiation (CRT) and others. in two institutions in the Czech Republic and analysed the potential predictive value of Methods: Stage II-IV RC pts treated with curative intent modalities between 2005-2023 at Mayo different RAS mutations. Results: Baseline characteristics: median age 65 (range 28-Clinic and University of Pittsburgh were evaluated. Eligible pts had pre and post-treatment tissue 84), female 32.8%, ECOG PS 0 in 32.8% and 1 in 64.9%, primary tumor location left colon available for analysis. Clinical characteristics, treatment, and outcome data were extracted from the Methods: RAS-trace is a pilot study to monitor RAS, BRAF, and PIK3CA mutation status by on DFS were established in some studies. However, it is unclear if these previously noted in 76.3%. The median line in which T/T was administered was 3 (range 2-8). Median medical record. QuantCRC extracted 15 features: %tumor, %stroma, tumor:stroma ratio, %TB/PDC, % ctDNA, using NGS-based Plasma-Safe-SeqS technology for RAS/BRAF wt (diagnosed from prognostic effects of RAS/BRAF mts will be maintained with the information provided number of T/T cycles administered was 3 (range 2-27). Median follow-up was mucin, %necrosis, %high-grade, %signet ring cells, tumor-infiltrating lymphocytes (TILs) per cm 2 of a tissue samples) mCRC treated with anti-EGFR mAb as a first-line chemotherapy. ctDNA-RAS/BRAF/PIK3CA status evaluated at baseline, 8, 12, 16, 20, 24, 36, 48 weeks and disease response of anti-EGFR mAb. The association of ctDNA status with survival outcomes will be HR=1.42 (95% CI 0.76 -2.64, p = NS), which was unchanged after excluding those with worse OS (6.6 vs 9.1 months, P=.02, HR 2.46). Conclusions: We did not confirm the Conclusions: Emergence of RAS/BRAF/PIK3CA mutations at 8 weeks may be related to the 0.4-4.4, p=NS). 48 pts were ctDNA+, with no difference in DFS by RAS mt status with G12 variants, 5 patients, 10.0 months, P=.028). BRAF mutation was associated with associated with depth of response and had a tendency of skin rashes $ Grade 2 (Table). The 12-m DFS in this cohort was 95.2% in RAS mt vs 97.9% in RAS wt (OR 1.25, 95% CI G12V, 45 patients, 10.5 m; for G12S, 7 patients, 16.1 m; for G12A, 11 patients, 7.6; other presence of liver metastases, tumor sidedness, or early tumor shrinkage, however, they were pts were ctDNA-ve with a DFS HR=1.81 for RAS mut vs wt (95% CI 0.57-5.73, p=0.30). different OS (for G12C, 7 patients, OS was 6.0 months; for G12D, 41 patients, 9.0 m; for both KRAS and BRAF mutations. ctDNA mutations at 8 weeks were not associated with the significant difference between ctDNA+ rates in RAS mt vs RAS wt pts (x2 p=0.41); 217 groups of patients. In KRAS G12 group we found that specific gene variants have mutations were detected in 3, 2, and 0 among the 39 patients, respectively. One patient had m (95% CI 5.52 -10.33-m) in ctDNA+ vs not reached in ctDNA-ve. There was no patients (P=.069; HR 1.75). Patients with KRAS G12 had no OS difference vs other shrinkage, depth of response or skin rash $Grade 2. At 8 weeks, RAS, BRAF, and PIK3CA BRAF V600E in 3.8% (n=10). After a median follow up of 16-m, the median was DFS 7.93-vs wt (P=.02; HR 2.08), vs other mutated (P=0.067; HR 1.75), vs KRAS G12 mutated not associated with the presence of liver metastases, tumor sidedness, early tumor sequencing and were included for this analysis, with RAS mutations in 44% (n=116) and P=.180). Patients with KRAS G13 had worse OS vs all other patients (P=.029; HR 1.97), spectively. One patient had both KRAS and BRAF mutations. Baseline ctDNA mutations were and RAS mt. Results: Within the INTERCEPT program, 265 pts had whole exome (9.1 months), KRAS G12 (9.1 m), KRAS G13 (5.6 m), and other RAS mutations (10.6 m, RAS, BRAF, and PIK3CA mutations were detected in 3, 3, and 1 of the 40 patients, re-including whole exome sequencing called by GATK-Mutect2 to assess for BRAFV600E mutated group (P=.50) was observed. OS in the defined groups was found: wtRAS group patients received mFOLFOX6 plus cetuximab (N=32) or panitumumab (N=8). At baseline, cohort of patients from the INTERCEPT program also had correlative analysis performed 57 (14.2%), and BRAF mutation in 14 (4.8%). No difference in OS in RAS wildtype (wt) vs and 40 and 39 were used in the analysis of ctDNA at baseline and 8 weeks, respectively. All performed along with routine surveillance visits (post-operatively and Q3 months). A KRAS G13 in 19 (4.7%), other RAS mutation in 25 (6.2%), non-specified RAS mutation in of ctDNA at baseline and 8 weeks are presented. Results: Forty-two patients were enrolled, evaluated with a tissue-informed ctDNA assay (Signatera). This ctDNA testing was detected in 54.2% patients. KRAS G12 mutation was found in 117 patients (29.1%), progression. The primary endpoint was the time to the acquired RAS mutations. The results with ctDNA testing for MRD. Methods: As part of the INTERCEPT program, pts with Stage II-IV CRC treated with curative intent at MD Anderson Cancer Center were tumor, %immature stroma (tumor bed), %inflammatory stroma (tumor bed), %mature stroma (tumor 32.4 months, 358 patients died (89.1%). Overall survival (OS) was 9.3 months (95% CI 8.7 to 10.3) and progression-free survival (PFS) 3.5 months (3.2 to 3.6). RAS mutation was bed), %immature (stromal region), %inflammatory (stromal region), and %mature (stromal region).||||

|Molecular and immune landscape by cyclin dependent kinase (CDK) 4/6 POLE variant phenotypic classification to enable identification of patients Tissue factor: A link between metastatic colorectal cancer and thrombosis in|Clinical/molecular features and prognostic significance of RAS mutant-low Clinicopathological features and clinical outcomes in individuals with Kru-Early onset metastatic colorectal cancer: Clinical-prognostic characteristics Novel potential mechanisms of acquired resistance to anti-EGFR monoclo-|Clinical/molecular features and prognostic significance of RAS mutant-low Clinicopathological features and clinical outcomes in individuals with Kru-Early onset metastatic colorectal cancer: Clinical-prognostic characteristics Novel potential mechanisms of acquired resistance to anti-EGFR monoclo-||

|expression and TP53 mutational status in mismatch repair deficient/ with colorectal cancer (CRC) who may benefit from immune checkpoint patients in the CALGB (Alliance)/SWOG 80405 trial. First Author: Sandra Algaze,|versus RAS mutant-high in patients with metastatic colorectal cancer. First kenberg tumors of colorectal origin. First Author: Colin P Bergstrom, Stanford and correlation to molecular profile. First Author: Andrea Pretta, Medical Oncology nal antibody (mAb) therapy detected in liquid biopsies (LBx) from patients|versus RAS mutant-high in patients with metastatic colorectal cancer. First kenberg tumors of colorectal origin. First Author: Colin P Bergstrom, Stanford and correlation to molecular profile. First Author: Andrea Pretta, Medical Oncology nal antibody (mAb) therapy detected in liquid biopsies (LBx) from patients||

|microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC). inhibition (ICI). First Author: Rachel Beth Keller, Foundation Medicine, Inc., Cambridge, Division of Medical Oncology, USC Norris Comprehensive Cancer Center, Keck School of|Author: Benoist Chibaudel, Department of Medical Oncology, Fondation Cognacq-Jay, University Medical Center, Stanford, CA Unit, University Hospital and University of Cagliari, Cagliari, Italy (pts) with advanced colorectal cancer (CRC). First Author: Christine Megerdichian|Author: Benoist Chibaudel, Department of Medical Oncology, Fondation Cognacq-Jay, University Medical Center, Stanford, CA Unit, University Hospital and University of Cagliari, Cagliari, Italy (pts) with advanced colorectal cancer (CRC). First Author: Christine Megerdichian||

|First Author: Alexandra Wong, Norris Comprehensive Cancer Center, Keck School of MA Medicine, Los Angeles, CA Medicine, University of Southern California, Los Angeles, CA Background: Pathogenic POLE (pPOLE) variants interfere with the exonuclease activity of Background: Tissue factor (TF) is a transmembrane protein that plays a crucial role in|Franco-British Hospital, Levallois-Perret, France Background: Addressing tumor heterogeneity is one of the main advantage of Background: Krukenberg tumors (KT) are metastases to the ovary generally originating Parseghian, The University of Texas MD Anderson Cancer Center, Houston, TX Background: Despite a reduction of both incidence and mortality of CRC in the elderly from a gastrointestinal primary such as colorectal carcinoma. The prognosis is poor with population, several studies published in the last decade have shown an increase in the Background: While several studies have explored the evolving clonal profile of mCRC|||

|Background: TP53 mutation (mut) has been reported to be associated with lower anti-tumor POLe during DNA replication, resulting in somatic ultramutation and conferring suscep-thrombosis. TF expression is elevated in various types of cancer, including colorectal cancer|liquid biopsy over tissue biopsy, as liquid biopsy is likely to better reflect the global KT, and clinicopathological features associated with clinical outcomes have not been incidence of early-onset CRC (EO-CRC). Clinical and prognostic data on this setting are under stress of anti-EGFR using circulating tumor DNA (ctDNA), heterogeneity and small|liquid biopsy over tissue biopsy, as liquid biopsy is likely to better reflect the global KT, and clinicopathological features associated with clinical outcomes have not been incidence of early-onset CRC (EO-CRC). Clinical and prognostic data on this setting are under stress of anti-EGFR using circulating tumor DNA (ctDNA), heterogeneity and small||

|). Co-mutations of TP53/SMAD4, KRAS/SMAD4, and TP53/KRAS/SMAD4 were associated with significantly worse OS compared to cases with no co-mutations (P=0.001, P=0.0002, P=0.003). Conclusions: Co-mutations in TP53, KRAS, and SMAD4 may serve as factors for predicting the effectiveness of preoperative treatment and prognosis in locally advanced rectal cancer. Research Sponsor: None. immunity and worse response to immune checkpoint inhibition (ICI) in CRC. Recent data suggest tibility to ICI. Historical classification of pPOLE relies on localization to the exonuclease (CRC) and is associated with more aggressive disease and poor prognosis. The aim of this that CDK4/6 inhibition may enhance the efficacy of ICI in CRC by modulation of TP53 pathway mediators. We sought to characterize the impact of CDK4/6 expression on mutational profile, tumor microenvironment (TME), and clinical outcomes in patients with dMMR/MSI-H CRC stratified by TP53 mut status. Methods: Tumor profiling was performed for 13,942 samples by NextGen Sequencing on DNA (592-gene panel or WES) and RNA (WTS) at Caris Life Sciences (Phoenix, AZ). Of these, 932 specimens were dMMR/MSI-H. Cohorts were created based on top (Q4) and bottom (Q1) quartiles of CDK4/6 RNA expression (transcripts per million) and further divided based on TP53 mut. Chi-square, Fishers-exact, and Mann Whitney tests were used to determine statistical significance and adjusted for multiple hypothesis testing by Benjamini-Hochberg (q , 0.05). Cell infiltration in the TME was estimated by quanTIseq. Insurance claims data was obtained to calculate ICI-survival using Kaplan-Meier estimates from the initiation of treatment to last contact. Results: CDK4 & 6 tumor expression levels positively correlated in our dataset (r = 0.53, P , 0.05) and were not significantly different in primary vs. metastatic sites. CDK6-Q4 tumors were enriched for mutations in APC, HNF1A, KRAS and DNMT3A, while CDK6-Q1 was associated with BRAF mutations and PDL1+ tumors (P , 0.05). Mutations in ARID1A, CDH1, KMT2A, FANCL, NF2 and BMPR1A showed opposite trends in CDK6-Q4 compared to Q1 depending on TP53 mut. CDK6-Q4 tumors were associated with higher expression of immune checkpoint genes including CTLA4, CD274, PDCD1LG12, LAG3, CD80, CD86, PDCD1, HAVCR2, IFNG (fold change [FC] Q4 vs Q1: 1.65-3.23, q , 0.05); alongside a TME characterized by higher infiltration rates of B cells, M2 macrophages, and NK cells (FC: 1.19-1.61, q , 0.05), independent of TP53 mut. The T-cell inflamed signature score was also higher in CDK6-Q4 vs Q1 (q , 0.05). Similar results were observed for CDK4. In patients with TP53 mut tumors, CDK6 expression greater than the median was associated with longer ICI survival (HR = 0.46, 95% CI 0.22-0.95, P = 0.032), whereas no difference was observed in patients not stratified by TP53 mut. Conclusions: Our comprehensive analysis is the first to show distinct mutational profiles according to TP53 mut status, and differential expression of immune-related genes and TME cell infiltration independent of TP53 mut in CDK4/6 high vs low dMMR/MSI-H CRC. In our series, CDK6 expression correlated with ICI treatment benefit in TP53 mut tumors, warranting further studies to explore the potential of targeting the CDK4/6 axis to enhance ICI efficacy in CRC. Research Sponsor: Partly supported by National Cancer Institute; Gloria Borges WunderGlo Foundation; Dhont Family Foundation; Gene Gregg Pancreas Research Fund; San Pedro Peninsula Cancer Guild; Daniel Butler Research Fund; V foundation for cancer research; Victoria and Philip Wilson Research Fund; Fong research project; Ming Hsieh research fund. domain (ED). We present the landscape of pPOLE variants in CRC according to a proposed phenotypic classification model. Methods: Comprehensive genomic profiling was per-formed on tissue (TBx) and liquid (LBx) biopsies during the course of clinical care. A POLE-specific variant classification model including tumor mutational burden (TMB), mutational signatures, and germline frequency was used to differentiate pPOLE from benign POLE (bPOLE) variants. Results: POLE variant status was evaluated in 455,965 TBx and 41,804 LBx pan-tumor. POLE alterations, including pPOLE and variants of unknown significance, were detected in 3.9% of samples with 7,404 discrete alleles observed. After applying the classification model, 30 variants were classified as pPOLE, representing 3.6% (751/20,601) of observed POLE variants. All pPOLE were localized to the ED and a majority were missense substitutions (29/30). There were an additional 620 ED variants categorized as bPOLE. CRC had the second highest prevalence of pPOLE variants (0.5%, 302/60,547). pPOLE variants were associated with ultramutation in CRC where the median tissue TMB was 183.0 mut/Mb, 1-2 orders of magnitude higher than for CRC harboring bPOLE variants (7.8 mut/Mb) or without POLE variants (3.5 mut/Mb). 32.2% of pPOLE CRC also had evidence of high microsatellite instability (MSI-H). Combined pPOLE + MSI-H was associated with markedly elevated TMB compared to either signature alone (344.4 versus 53.1 and 151.3 mut/Mb for bPOLE + MSI-H and pPOLE + MS-Stable, respectively). A small minority of CRC tumors with pPOLE variants (7/298, 2.3%) had low TMB (,10 mut/Mb). However, this was associated with a low pPOLE variant allele frequency (VAF; median 2.8% versus 24.0% for tumors w/ TMB $10, p , .0001) pointing to low tumor purity and likely an underestimation of TMB. While targetable alterations (e.g., homologous recombination repair [HR] gene variants) were enriched in pPOLE tumors, these tumors had a low rate of HR deficiency (HRD) as determined by a computational algorithm (HRDsig), suggesting these are likely incidental monoallelic variants. Conclusions: A POLE phenotype-specific classification model iden-tified pPOLE variants associated with ultramutation in CRC. Co-occurrence of pPOLE and MSI-H in CRC is common and has a synergistic effect leading to even higher TMB. We hypothesize that pPOLE detection predicts ultramutation and response to ICI even when TMB is under-detected due to low tumor purity. Caution is advised for therapy selection based on co-alterations in the setting of pPOLE due to an abundance of incidental variants. study was to evaluate TF expression in patients (pts) with metastatic CRC (mCRC) enrolled in the CALGB (Alliance)/SWOG 80405 clinical trial. Understanding the relationship between TF expression and mCRC will provide insights into the role of coagulation in the progression and prognosis of this disease and may have therapeutic implications, particularly in the setting of recent approval of a TF antibody drug conjugate for metastatic cervical cancer and other agents in the pipeline. Methods: 433 pts with mCRC treated with bevacizumab (Bev, n = 226) or cetuximab (Cet, n =207) in combination with first-line chemotherapy in CALGB/SWOG 80405 were included in the analysis.TF RNA was isolated from FFPE tumor samples and sequenced on the HiSeq 2500 (Illumina). Overall survival (OS) and progression-free survival (PFS) were compared between groups of pts categorized by tertiles of TF expression: high (H), medium (M) and low (L). Sensitivity analyses were conducted after stratifying by side. Logrank P-values describe differences without adjustment for pt characteristics. Transcriptome-wide gene association analysis was performed using linear regression, adjusting for age, sex, ethnicity, ECOG PS, location, number of metastases, KRAS, MSI status, treatment with FOLFOX or FOLFIRI, and the first 3 principal components from the RNA-seq data. Gene Ontology enrichment analysis was conducted with the top 100 TF-associated genes. Results: TF expression is associated with genes related to maintenance of epithelium, cell adhesion, and migration, immunoregulatory cytokine production, and metabolic, HER2, and MAP/Kinase pathways. TF-L showed significantly longer median (m)PFS (13.4 vs 10.1 vs 9.2 months (mo), p=0.0022) and mOS (35.4 vs 30.9 vs 25.2, p=0.0051) in the entire cohort. In Cet treated pts, TF-L had significantly longer mOS (41.3 vs 29.9 vs 26.1 mo, p=0.0013). In pts treated with FOLFOX, TF-L had significantly longer PFS (13.2 vs 10.9 vs 8.2 mo, p=0.0014) and OS (33.4 vs 30.9 vs 22.4 mo, p=0.0044). Pts with liver metastases and TF-H had worse PFS (9.2 vs 9.9 vs 13.5 mo, p=0.006) and OS (23.6 vs 29.9 vs 35.1 mo, p=0.016). Conclusions: Our results suggest that pts with TF-L tumors with liver metastases have improved prognosis compared to pts with TF-H and may benefit from FOLFOX and Cet-based treatment. Findings provide rationale for further evaluation of TF as a predictive biomarker and potential therapeutic target in CRC. Trial Identifier NCT00265850. Support: P30CA014089, U10CA180821, U10CA180882, U10CA180820 and UG1CA233277; UG1CA180830, U10CA180888; Pfizer, Genentech. https://acknowledgments.alliancefound.org. Research Sponsor: None. Research Sponsor: Foundation Medicine, Inc.|molecular profile (primary tumor site and metastatic disease). Variant Allele Frequency (VAF) represents the fraction of sequencing reads in which a variant is observed. The aim was to evaluate the prognostic value of circulating tumor (ct) VAF for KRAS and NRAS genes in patients with ctRAS mutant metastatic colorectal cancer (MCRC). Methods: Circulating comprehensive genomic profiling using FoundationOne Liquid CDx (FO-Liq) was proposed to patients with histologically proven or highly suspected solid tumor whatever treatment line. FO-Liq is a next generation sequencing panel of 310 cancer related genes and 3 genomic signatures (blood tumor mutational burden (bTMB), microsatellite instability (MSI) and tumor fraction (TF)). The optimal threshold for ctVAF was determined by calculating Harrell's C discrimination index extended for survival data. The primary endpoint was overall survival (OS). Results: From October 2020 to June 2023, 740 patients were screened for circulating molecular profiling. In the co-lorectal cohort (N=201), 198 (98.5%) patients had metastatic disease (ctRAS/BRAF wild-type, N=76 (38.4%) ; ctRAS mutant, N=106 (53.5%) and ctBRAF V600E mutant, N=16 (8.1%)). The optimal threshold for ctVAF RAS was 5% (C-index 0.67, 95% CI 0.62-0.73 ; P,0.0001). Among patients with ctRAS mutant MCRC, 43 (40.6%) were ctRAS mutant-Low (VAF RAS ,5%) and 63 (59.4%) were ctRAS mutant-High (VAF RAS $5%). Median follow-up was 18.5 months (95% CI 15.3-34.5). There was a significant increase in the the risk of death for RAS mutant-High compared to RAS mutant-Low (HR 2.81, 95% CI 1.70-4.63; P,0.001). Patients with RAS mutant-low variants had the same prognosis that RAS/BRAF wild-type profile (HR 1.22 ; P=0.573), and patients with RAS mutant-high variants had the same prognosis that BRAF mutant profile (HR 0.82, P=0.563). The factors associated with RAS mutant-High profile were : bTMB-High, TF-High, RAS G12A and G13D variants. MAP kinase, TGFb and Wnt signaling pathways and BRCA1-2 genes were more frequently altered in patients with ctRAS mutant-High tumors. We observed a transient decrease of VAF RAS in second-line setting. Conclusions: The circulating VAF of RAS genes enables to split RAS mutant-Low (favorable prognosis similar to RAS/ BRAF wild-type) from RAS mutant-High (poorer prognosis similar to BRAF mutant) metastatic colorectal cancer. These results provide further insights into prognostication and therapeutic strategies in patients with RAS mutant metastatic colorectal cancer. Research Sponsor: None. extensively studied. The study aimed to investigate the associations of clinicopatho-cohorts limit our understanding of acquired genomic alterations (GAs) associated with limited and conflicting. The aim of our study was to evaluate the clinical, prognostic, and logical features with outcomes in patients with KT of colorectal carcinoma (CRC) origin. Methods: This retrospective study utilized medical records and patient registries to identify 160 patients with a confirmed histopathological diagnosis of KT at Stanford University Medical Center between 2000 and 2020. Data collection included demo-graphics, historical, clinicopathological, treatment and outcome variables. The primary tumor type was (N, %): CRC (101, 63.1%); gastric (24, 15%), breast (13, 8.1%); small bowel (10, 6.2%), other (12, 7.5%). Statistical analysis was performed using Chi-squared, Mann-Whitney U, and log-rank Kaplan-Meier analysis. Results: Analysis of the CRC cohort subdivided by location of the primary, N: 45 vs. 56, right colon (R) vs. left colon (L) revealed no significant difference in median age at diagnosis of KT, race/ethnicity, oligometastatic disease, histopathological differentiation or ovarian tumor volume. Patients with R vs L sided CRC primaries had a higher proportion of synchronous presentation at the time of KT diagnosis (75.6% vs 41.1%, R vs L, p,0.001). Time to progression was not different, but overall survival (OS) was shorter in R CRC (767 vs. 1246 days, R vs. L, p ,0.01). By Kaplan-Meier analysis, patients with R CRC had a shorter OS (log-rank p=0.016). In the subgroup with unilateral KT, R sided CRC primaries in-volved the R ovary (85%) whereas L-sided CRC primaries involved the L ovary (70%) (x2, p,0.002). Patient with bilateral (B) versus unilateral (U) had a larger ovarian tumor volume (2,073cm 3 vs. 307 cm 3 , p,0.01) but no difference in oligometastatic disease, chronicity, time to progression or overall survival. There was no statistical difference (p=0.93) between the association of bilateral KT inter-ovarian tumor size and CRC Laterality within individual patients. Conclusions: In this study, KT tumors predomi-nantly originate from CRC. The clinical features of R versus L CRC, such as chronicity and OS are conveyed prognostically in patients with KT. Individuals with L CRC exhibited a better overall prognosis compared to those with R CRC. In patients with unilateral KT metastasis to ipsilateral ovary is significantly associated with location of CRC and is suggestive of a retrograde lymphatic or transcoelomic route of metastatic spread. Further studies are needed to confirm these findings and to elucidate ovarian organ tropism mediators that facilitate development and growth in metastatic ovarian cancer. Research Sponsor: None. EGFR resistance. Methods: CRC LBx were profiled with FoundationOne Liquid CDx, which molecular differences in a large group of patients (pts) with early onset mCRC. reports GAs in 324 cancer-related genes. Foundation Medicine's (FMI) ctDNA tumor Methods: We collected data from 589 metastatic EO-CRC from 4 different Italian In-fraction (TF) is a composite algorithm prioritizing aneuploidy at higher levels and variant stitutions. A historical control group of 316 pts . 50 year old was also included in the allele frequency (VAF) of canonical alterations at lower levels. Variants were considered analysis. All pts had one or more metastatic sites, molecular profiling available (in-cluding RAS, BRAF, and MSI status), and underwent at least one line of treatment. The main objective of the study was to evaluate clinical outcome in terms of median overall survival for the global population of EO-CRC pts and in different molecular subgroups according to RAS and BRAF status. Results: In the EO-CRC group median age was 44 (66) and 67 (611) in the historical control group. M/F ratios were 2:1 and 1:1, re-spectively. In the overall population mOS was 34,1 in EO-CRC pts vs 42,0 months (mo) (p = 0,0006) in the control group. In the RAS/BRAF mutated subgroup mOS in EO-CRC pts was 28,6 vs 36,0 mo in the control group (p = 0,0065). In RAS/BRAF wild type subgroup mOS in EO-CRC pts was 44,1 vs 49 mo (p = 0,13). Finally, in the BRAF V600E mutated subgroup EO-CRC pts showed a 16 mo mOS vs 26 mo (p = 0,04). In the overall population mPFS was 12,0 in EO-CRC pts vs 10,0 mo (p = 0,02) in the control group. Furthermore, the overall response rate (ORR) was 53% in EO-CRC and 69% in LO-CRC. Conclusions: Our work including a large population of EO-CRC pts indicates a general worse prognosis for pts with early onset colorectal cancer compared to late onsets. Interestingly this seems to occur regardless of the molecular status. On the other hand findings in the RAS/BRAF wild type population might also suggest a less unfavourable impact of EO-CRC on prognosis possibly related to anti-EGFR therapy. Subsequent investigations will be needed to further understand the specific clinical and molecular characteristics of this growing group of pts to better define the more appropriate treatment strategy. Research Sponsor: None. clonal at VAF/TF $25%, subclonal at ,25%. Among 4,546 non-MSI-H LBx, 2,776 (61%) had TF $1% and were used in this analysis. A subset of pts had treatment data in the US-based de-identified Flatiron Health-FM real-world clinico-genomic database (CGDB), originating from ~280 US cancer clinics (01/2011-03/2023). Results: 1,349 (49%) LBx had a clonal RAS GA, 107 (3.9%) had a clonal BRAF V600E, and 1,320 (48%) had no clonal RAS pathway driver GA. GAs in EGFR and MAP2K1 were significantly (FDR,0.0001) more common in LBx with no clonal RAS GA (162, 11%; 105, 7.4%) than with one (27, 2.0%; 24, 1.8%), consistent with prior reports of these GAs appearing in the setting of acquired resistance to anti-EGFR mAb. The 362 LBx with GAs in EGFR, MAP2K1, or subclonal RAS GAs (indicators of anti-EGFR mAb exposure based on a validated exposure signature) were compared to the 1349 LBx with a clonal RAS mutation. Post anti-EGFR LBx were significantly enriched in BRAF, TP53, FGFR3, PTPN11, ERRFI1, and MLH1 GAs (FDR,0.05) and all but TP53 had median VAF/TF ,25%. The majority of clonal BRAF GAs were V600E (14/19, 74%) while the majority of subclonal BRAF GAs were Class 2 (36/61, 59%). Other subclonal GAs in receptor tyrosine kinases and RAS pathway components detected in these LBx included: NF1 (26), ROS1 (9), ALK (7), MET (7), RAF1 (7), FGFR2 (6), HRAS (6), MAP2K2 (6), and RET (4). 18/362 (4.4%) of the LBx had $2 of these resistance GAs (up to 5 per LBx). In CGDB, 14/25 (56%) LBx collected at progression had potential resistance GAs (median 2, maximum 10). LBx collected at progression (N = 25) had higher prevalence of GA in EGFR (28% vs. 2.3%, p=0.0003), KRAS (28% vs. 0%, p,0.0001), NRAS (20% vs. 0%, p=0.0002) and MAP2K1 (20% vs. 2.3%, p=0.008) than LBx collected before therapy start (N = 87). Conclusions: This study reports on the largest set of LBx from pts likely exposed to anti-EGFR published to date. LBx can provide a more comprehensive and quantitative picture of acquired re-sistance to anti-EGFR in CRC than tissue biopsy, including some potential novel mech-anisms identified in this study. Further investigation into whether detection of resistance can inform clinical decisions about timing of anti-EGFR mAb use and rechallenge is warranted. Research Sponsor: Foundation Medicine Inc.|molecular profile (primary tumor site and metastatic disease). Variant Allele Frequency (VAF) represents the fraction of sequencing reads in which a variant is observed. The aim was to evaluate the prognostic value of circulating tumor (ct) VAF for KRAS and NRAS genes in patients with ctRAS mutant metastatic colorectal cancer (MCRC). Methods: Circulating comprehensive genomic profiling using FoundationOne Liquid CDx (FO-Liq) was proposed to patients with histologically proven or highly suspected solid tumor whatever treatment line. FO-Liq is a next generation sequencing panel of 310 cancer related genes and 3 genomic signatures (blood tumor mutational burden (bTMB), microsatellite instability (MSI) and tumor fraction (TF)). The optimal threshold for ctVAF was determined by calculating Harrell's C discrimination index extended for survival data. The primary endpoint was overall survival (OS). Results: From October 2020 to June 2023, 740 patients were screened for circulating molecular profiling. In the co-lorectal cohort (N=201), 198 (98.5%) patients had metastatic disease (ctRAS/BRAF wild-type, N=76 (38.4%) ; ctRAS mutant, N=106 (53.5%) and ctBRAF V600E mutant, N=16 (8.1%)). The optimal threshold for ctVAF RAS was 5% (C-index 0.67, 95% CI 0.62-0.73 ; P,0.0001). Among patients with ctRAS mutant MCRC, 43 (40.6%) were ctRAS mutant-Low (VAF RAS ,5%) and 63 (59.4%) were ctRAS mutant-High (VAF RAS $5%). Median follow-up was 18.5 months (95% CI 15.3-34.5). There was a significant increase in the the risk of death for RAS mutant-High compared to RAS mutant-Low (HR 2.81, 95% CI 1.70-4.63; P,0.001). Patients with RAS mutant-low variants had the same prognosis that RAS/BRAF wild-type profile (HR 1.22 ; P=0.573), and patients with RAS mutant-high variants had the same prognosis that BRAF mutant profile (HR 0.82, P=0.563). The factors associated with RAS mutant-High profile were : bTMB-High, TF-High, RAS G12A and G13D variants. MAP kinase, TGFb and Wnt signaling pathways and BRCA1-2 genes were more frequently altered in patients with ctRAS mutant-High tumors. We observed a transient decrease of VAF RAS in second-line setting. Conclusions: The circulating VAF of RAS genes enables to split RAS mutant-Low (favorable prognosis similar to RAS/ BRAF wild-type) from RAS mutant-High (poorer prognosis similar to BRAF mutant) metastatic colorectal cancer. These results provide further insights into prognostication and therapeutic strategies in patients with RAS mutant metastatic colorectal cancer. Research Sponsor: None. extensively studied. The study aimed to investigate the associations of clinicopatho-cohorts limit our understanding of acquired genomic alterations (GAs) associated with limited and conflicting. The aim of our study was to evaluate the clinical, prognostic, and logical features with outcomes in patients with KT of colorectal carcinoma (CRC) origin. Methods: This retrospective study utilized medical records and patient registries to identify 160 patients with a confirmed histopathological diagnosis of KT at Stanford University Medical Center between 2000 and 2020. Data collection included demo-graphics, historical, clinicopathological, treatment and outcome variables. The primary tumor type was (N, %): CRC (101, 63.1%); gastric (24, 15%), breast (13, 8.1%); small bowel (10, 6.2%), other (12, 7.5%). Statistical analysis was performed using Chi-squared, Mann-Whitney U, and log-rank Kaplan-Meier analysis. Results: Analysis of the CRC cohort subdivided by location of the primary, N: 45 vs. 56, right colon (R) vs. left colon (L) revealed no significant difference in median age at diagnosis of KT, race/ethnicity, oligometastatic disease, histopathological differentiation or ovarian tumor volume. Patients with R vs L sided CRC primaries had a higher proportion of synchronous presentation at the time of KT diagnosis (75.6% vs 41.1%, R vs L, p,0.001). Time to progression was not different, but overall survival (OS) was shorter in R CRC (767 vs. 1246 days, R vs. L, p ,0.01). By Kaplan-Meier analysis, patients with R CRC had a shorter OS (log-rank p=0.016). In the subgroup with unilateral KT, R sided CRC primaries in-volved the R ovary (85%) whereas L-sided CRC primaries involved the L ovary (70%) (x2, p,0.002). Patient with bilateral (B) versus unilateral (U) had a larger ovarian tumor volume (2,073cm 3 vs. 307 cm 3 , p,0.01) but no difference in oligometastatic disease, chronicity, time to progression or overall survival. There was no statistical difference (p=0.93) between the association of bilateral KT inter-ovarian tumor size and CRC Laterality within individual patients. Conclusions: In this study, KT tumors predomi-nantly originate from CRC. The clinical features of R versus L CRC, such as chronicity and OS are conveyed prognostically in patients with KT. Individuals with L CRC exhibited a better overall prognosis compared to those with R CRC. In patients with unilateral KT metastasis to ipsilateral ovary is significantly associated with location of CRC and is suggestive of a retrograde lymphatic or transcoelomic route of metastatic spread. Further studies are needed to confirm these findings and to elucidate ovarian organ tropism mediators that facilitate development and growth in metastatic ovarian cancer. Research Sponsor: None. EGFR resistance. Methods: CRC LBx were profiled with FoundationOne Liquid CDx, which molecular differences in a large group of patients (pts) with early onset mCRC. reports GAs in 324 cancer-related genes. Foundation Medicine's (FMI) ctDNA tumor Methods: We collected data from 589 metastatic EO-CRC from 4 different Italian In-fraction (TF) is a composite algorithm prioritizing aneuploidy at higher levels and variant stitutions. A historical control group of 316 pts . 50 year old was also included in the allele frequency (VAF) of canonical alterations at lower levels. Variants were considered analysis. All pts had one or more metastatic sites, molecular profiling available (in-cluding RAS, BRAF, and MSI status), and underwent at least one line of treatment. The main objective of the study was to evaluate clinical outcome in terms of median overall survival for the global population of EO-CRC pts and in different molecular subgroups according to RAS and BRAF status. Results: In the EO-CRC group median age was 44 (66) and 67 (611) in the historical control group. M/F ratios were 2:1 and 1:1, re-spectively. In the overall population mOS was 34,1 in EO-CRC pts vs 42,0 months (mo) (p = 0,0006) in the control group. In the RAS/BRAF mutated subgroup mOS in EO-CRC pts was 28,6 vs 36,0 mo in the control group (p = 0,0065). In RAS/BRAF wild type subgroup mOS in EO-CRC pts was 44,1 vs 49 mo (p = 0,13). Finally, in the BRAF V600E mutated subgroup EO-CRC pts showed a 16 mo mOS vs 26 mo (p = 0,04). In the overall population mPFS was 12,0 in EO-CRC pts vs 10,0 mo (p = 0,02) in the control group. Furthermore, the overall response rate (ORR) was 53% in EO-CRC and 69% in LO-CRC. Conclusions: Our work including a large population of EO-CRC pts indicates a general worse prognosis for pts with early onset colorectal cancer compared to late onsets. Interestingly this seems to occur regardless of the molecular status. On the other hand findings in the RAS/BRAF wild type population might also suggest a less unfavourable impact of EO-CRC on prognosis possibly related to anti-EGFR therapy. Subsequent investigations will be needed to further understand the specific clinical and molecular characteristics of this growing group of pts to better define the more appropriate treatment strategy. Research Sponsor: None. clonal at VAF/TF $25%, subclonal at ,25%. Among 4,546 non-MSI-H LBx, 2,776 (61%) had TF $1% and were used in this analysis. A subset of pts had treatment data in the US-based de-identified Flatiron Health-FM real-world clinico-genomic database (CGDB), originating from ~280 US cancer clinics (01/2011-03/2023). Results: 1,349 (49%) LBx had a clonal RAS GA, 107 (3.9%) had a clonal BRAF V600E, and 1,320 (48%) had no clonal RAS pathway driver GA. GAs in EGFR and MAP2K1 were significantly (FDR,0.0001) more common in LBx with no clonal RAS GA (162, 11%; 105, 7.4%) than with one (27, 2.0%; 24, 1.8%), consistent with prior reports of these GAs appearing in the setting of acquired resistance to anti-EGFR mAb. The 362 LBx with GAs in EGFR, MAP2K1, or subclonal RAS GAs (indicators of anti-EGFR mAb exposure based on a validated exposure signature) were compared to the 1349 LBx with a clonal RAS mutation. Post anti-EGFR LBx were significantly enriched in BRAF, TP53, FGFR3, PTPN11, ERRFI1, and MLH1 GAs (FDR,0.05) and all but TP53 had median VAF/TF ,25%. The majority of clonal BRAF GAs were V600E (14/19, 74%) while the majority of subclonal BRAF GAs were Class 2 (36/61, 59%). Other subclonal GAs in receptor tyrosine kinases and RAS pathway components detected in these LBx included: NF1 (26), ROS1 (9), ALK (7), MET (7), RAF1 (7), FGFR2 (6), HRAS (6), MAP2K2 (6), and RET (4). 18/362 (4.4%) of the LBx had $2 of these resistance GAs (up to 5 per LBx). In CGDB, 14/25 (56%) LBx collected at progression had potential resistance GAs (median 2, maximum 10). LBx collected at progression (N = 25) had higher prevalence of GA in EGFR (28% vs. 2.3%, p=0.0003), KRAS (28% vs. 0%, p,0.0001), NRAS (20% vs. 0%, p=0.0002) and MAP2K1 (20% vs. 2.3%, p=0.008) than LBx collected before therapy start (N = 87). Conclusions: This study reports on the largest set of LBx from pts likely exposed to anti-EGFR published to date. LBx can provide a more comprehensive and quantitative picture of acquired re-sistance to anti-EGFR in CRC than tissue biopsy, including some potential novel mech-anisms identified in this study. Further investigation into whether detection of resistance can inform clinical decisions about timing of anti-EGFR mAb use and rechallenge is warranted. Research Sponsor: Foundation Medicine Inc.||

|||||||||206|Poster Session| |---|---|---|---|---|---|---|---|---|---|

|Association of pathologic nodal status with minimal residual disease after|Prognostic factors for anti-angiogenic treatment in patients with metastatic|Prognostic factors for anti-angiogenic treatment in patients with metastatic||||||||

|neoadjuvant treatment and resection of locally advanced rectal cancer. First|colorectal cancer: New insights for an old issue from a single institution|colorectal cancer: New insights for an old issue from a single institution||||||||

|Author: Abhineet Uppal, Department of Colon and Rectal Surgery, The University of|experience. First Author: Eleonora Lai, Medical Oncology Unit, University Hospital and|experience. First Author: Eleonora Lai, Medical Oncology Unit, University Hospital and||||||||

|Texas MD Anderson Cancer Center, Houston, TX|||||University of Cagliari, Cagliari, Italy|||||

|Background: Studies have shown that minimal residual disease (MRD) identified by|Background: Anti-angiogenic drugs represent a cornerstone of metastatic colorectal|Background: Anti-angiogenic drugs represent a cornerstone of metastatic colorectal||||||||

|detection of circulating tumor DNA (ctDNA) is associated with recurrence after surgical|cancer (mCRC) patients (pts) treatment. Currently, no prognostic/predictive biomarkers|cancer (mCRC) patients (pts) treatment. Currently, no prognostic/predictive biomarkers||||||||

|resection of colorectal cancer. Though multiple trials are evaluating the use of ctDNA to|were validated to identify who is more likely to benefit from these agents. We performed|were validated to identify who is more likely to benefit from these agents. We performed||||||||

|guide adjuvant therapy, data on the utility of ctDNA after neoadjuvant therapy is limited.|at our Centre a retrospective research to assess potential prognostic/predictive factors|at our Centre a retrospective research to assess potential prognostic/predictive factors||||||||

|In this study, we evaluated the associations between ctDNA and recurrence after|in this population. Methods: We retrospectively collected laboratory, radiological and|in this population. Methods: We retrospectively collected laboratory, radiological and||||||||

|neoadjuvant treatment and resection of rectal cancer (LARC). Methods: Consecutive|clinical data of mCRC pts receiving anti-angiogenic agents at the Medical Oncology Unit|clinical data of mCRC pts receiving anti-angiogenic agents at the Medical Oncology Unit||||||||

|patients with primary rectal cancer treated with neoadjuvant systemic therapy and/or|of Cagliari University Hospital (2018-09/2023) in order to assess their correlation with|of Cagliari University Hospital (2018-09/2023) in order to assess their correlation with||||||||

|chemoradiotherapy followed by resection between 12/2020-4/2023 were identified.|overall survival (OS) and progression free survival (PFS) from the treatment start.|overall survival (OS) and progression free survival (PFS) from the treatment start.||||||||

|Patients were tested for ctDNA via the MD Anderson INTERCEPT platform using a high-|Statistical analysis was performed with MedCalc (survival distribution: Kaplan-Meier;|Statistical analysis was performed with MedCalc (survival distribution: Kaplan-Meier;||||||||

|sensitivity patient informed assay. Patients with metastases or a first ctDNA test more|survival comparison: log-rank test; cut-off: ROC curves). Results: Globally, 32 mCRC pts|survival comparison: log-rank test; cut-off: ROC curves). Results: Globally, 32 mCRC pts||||||||

|than 3 months after resection were excluded. MRI-determined stage, extramural|were included in our research (19 male, 13 female; 12 RAS wild-type, 21 left-sided|were included in our research (19 male, 13 female; 12 RAS wild-type, 21 left-sided||||||||

|vascular invasion (mrEMVI), pelvic sidewall adenopathy (PSW), pathologic lympho-|primary). 10 received anti-angiogenic drugs in the 1st-line, 12 in the 2nd-line (bev-|primary). 10 received anti-angiogenic drugs in the 1st-line, 12 in the 2nd-line (bev-||||||||

|vascular invasion (LVI), perineural invasion (PNI) and tumor regression grade (TRG) were|acizumab and aflibercept) and 10 in 1st-2nd line. Median OS was 34.8 months (m) (95%|acizumab and aflibercept) and 10 in 1st-2nd line. Median OS was 34.8 months (m) (95%||||||||

|collected. Associations between these factors and ctDNA status were analyzed with|CI:24.7-41.6). We observed a statistically significant improve in OS (34.8 months [m]|CI:24.7-41.6). We observed a statistically significant improve in OS (34.8 months [m]||||||||

|Fischer's exact test. Recurrence free survival (RFS) was analyzed with the log-rank test.|versus [vs] 8.2 m) in pts with higher monocyte count (.0.3x10 3 /mL; 95%CI 26.5-39.5 vs|versus [vs] 8.2 m) in pts with higher monocyte count (.0.3x10 3 /mL; 95%CI 26.5-39.5 vs||||||||

|(Bangkok, Thailand) were extracted. Patients who clinically suspected familial ade-|biomarkers are major focus areas in immuno-oncology. Methods: Patients with previously||||||||||||||

|nomatous polyposis were excluded. Gene mutational analysis was performed by next-|untreated, unresectable abdominal metastases from MSS/pMMR-CRC were randomly||||||||||||||

|cases with MSI discrepancy (6 cases), 83% (5/6) of the patients showed a transition from MSS to MSI-H from biopsy to surgery. Interestingly, all eight patients who received neoadjuvant chemotherapy maintained an unchanged MSI status. However, in one patient who received adjuvant treatment and underwent a repeat biopsy after surgery, the MSI status exhibited alterations. Further analysis of clonal evolution revealed that this hetero-geneity stemmed from the disappearance of the original clones and the emergence of new clones. Additionally, the NGS panel exhibited strong concordance with MSI-PCR and generation sequencing (NGS) using an Oncomine Comprehensive Assay Plus kit (Thermo Fisher Scientific, Inc., Waltham, MA, USA) and compared with previous reported molecular data in adult-onset CRC from our group. Results: The top 5 mutations frequency observed were TP53, KRAS, FBXW7, PIK3CA, and SMAD4 mutations which were comparable to what reported in adult-onset CRC. However, FBXW7, PIK3CA, NOTCH1, FGFR3, ERBB2, and PTEN were reported more frequent in AYA group. No difference in number of KRAS, NRAS, and BRAF mutations among 2 groups. Table below shows key cancer genes mutation frequencies. Conclusions: This study is the com-prehensive report hotspot mutations using NGS in sporadic AYA-onset sporadic CRC patients. The most commonly identified gene mutation frequencies among AYA-onset were similar to those reported in adult-onset, except for FBXW7, PIK3CA, NOTCH1, FGFR3, ERBB2, and PTEN mutations that had a slightly higher frequency. Further studies on larger sample set for genetic and epigenetic landscape are required. Research Sponsor: None. high accuracy, sensitivity and specificity with an AUC of 0.942 after rigorous validation. Conclusions: The study revealed a high concordance in MSI status between paired % Mutation frequency in AYA onset % Mutation frequency in adult onset Genes (n=90) (n=107) biopsy and surgical samples by employing a custom MSI-NGS panel for MSI status detection, providing reliable basis for further research in this field. Moreover, neo-TP53 51 60.2 KRAS 47 47.2 adjuvant chemotherapy seemed to have no impact on MSI status in our study, whereas postoperative adjuvant chemotherapy may influence changes in MSI status, highlighting the necessity of reevaluating MSI status after surgery. The findings also underscore the potential of NGS-based MSI detection as a valuable tool for clinical decision-making. FBXW7 23 14.8 PIK3CA 20 12 SMAD4 13 9.3 NOTCH1 11 1.9 FGFR3 9 3 . 7|assigned to the oxaliplatin-based standard Nordic FLOX regimen (control arm) or 2 FLOX cycles followed by 2 ICB (nivolumab) cycles in a repeat sequential schedule (experimental arm). Radiologic response assessment was done every 8 weeks, and the study arms reached identical primary endpoint -median progression-free survival (PFS) 9.3 months. Experimental-arm patients at one study center had peripheral blood mononuclear cells (PBMC) prepared at study entry (V1), after the initial 2 FLOX cycles (V3), and after the succeeding 2 nivolumab cycles (V5). The PBMC were incubated with 19 cell-surface an-tibodies and analyzed by mass cytometry. Patients were categorized in PFS .9.3 months (improved; n = 7) or PFS ,9.3 months (shortened; n = 6). Live cell clusters were identified by hierarchically applying automated 1D gates to the available lineage markers. After gating, all cells were assigned to soft clusters according to phenotypes. The cluster sizes were used to compute the differential abundance of immune-cell populations and a Peacock test assessed multivariate changes between the improved and shortened PFS groups. Results: Circulating CD4+ (Th) cells and CD27+IgD+ (NSwM-B) cells were concurrently enriched in the improved PFS group. After the initial 2 FLOX cycles (V3), median increase (from V1) was 2.89% (of lymphocyte count) for Th cells and 0.54% (of leukocyte count) for NSwM-B cells (p , 0.001). Continued responses occurred over the succeeding 2 nivolumab cycles (until V5) with median increase of 1.19% for Th cells and 0.19% for NSwM-B cells (p , 0.001). The association between the immune-cell alterations and PFS was validated by categorizing the cases in above or below the median increase in Th and NSwM-B cell populations from V1 to V5. The high-increase group achieved median PFS 15.0 months (95% CI, 10.8-19.2) compared to 4.0 months (95% CI, 1.9-22.1) for the low-increase group (log-rank; p = 0.002). Conclusions: This unsupervised analysis of high-dimensional PBMC data||||||||||||||

|Research Sponsor: None. ERBB2 PTEN ALK BRAF NRAS|9 8 6 3 2|5 . 6 4 . 6 4 . 6 1 . 9 2 . 8|from a limited case number revealed that circulating Th and NSwM-B cell populations may mediate ICB responsiveness invoked by short-course oxaliplatin-based chemotherapy in patients with abdominal metastases from MSS/pMMR-CRC. Owing to weaknesses of such a post-hoc analysis, further studies are needed to confirm the generalizability of these||||||||||||

|MET|2|0 . 9|findings. Clinical trial information: NCT003388190. Research Sponsor: None.||||||||||||

|Comprehensive genomic analysis of molecular residual disease based on|Clinical utility of upfront circulating tumor DNA (ctDNA) genotyping to guide|Clinical utility of upfront circulating tumor DNA (ctDNA) genotyping to guide|Clinical utility of upfront circulating tumor DNA (ctDNA) genotyping to guide|Clinical utility of upfront circulating tumor DNA (ctDNA) genotyping to guide|Clinical utility of upfront circulating tumor DNA (ctDNA) genotyping to guide||

|circulating tumor DNA in patients with postoperative colorectal cancer. First|first-line therapy in patients (pts) with metastatic colorectal cancer (mCRC):|first-line therapy in patients (pts) with metastatic colorectal cancer (mCRC):|first-line therapy in patients (pts) with metastatic colorectal cancer (mCRC):|first-line therapy in patients (pts) with metastatic colorectal cancer (mCRC):|first-line therapy in patients (pts) with metastatic colorectal cancer (mCRC):||

|Author: Qingqi Hong, Department of Gastrointestinal Oncology Surgery, The First Af-|A GOZILA substudy. First Author: Yu Aoki, Department of Gastroenterology and|A GOZILA substudy. First Author: Yu Aoki, Department of Gastroenterology and|A GOZILA substudy. First Author: Yu Aoki, Department of Gastroenterology and|A GOZILA substudy. First Author: Yu Aoki, Department of Gastroenterology and|A GOZILA substudy. First Author: Yu Aoki, Department of Gastroenterology and||

|filiated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen,|Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan|Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan|Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan|Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan|Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan||

|Fujian, China||Background: The clinical utility of upfront ctDNA genomic profiling is not established in|Background: The clinical utility of upfront ctDNA genomic profiling is not established in|Background: The clinical utility of upfront ctDNA genomic profiling is not established in|Background: The clinical utility of upfront ctDNA genomic profiling is not established in|Background: The clinical utility of upfront ctDNA genomic profiling is not established in|

|Background: Despite receiving curative resection, a considerable percentage of co-|treatment (tx)-naïve pts with mCRC. Methods: GOZILA is a nationwide plasma genomic|treatment (tx)-naïve pts with mCRC. Methods: GOZILA is a nationwide plasma genomic|treatment (tx)-naïve pts with mCRC. Methods: GOZILA is a nationwide plasma genomic|treatment (tx)-naïve pts with mCRC. Methods: GOZILA is a nationwide plasma genomic|treatment (tx)-naïve pts with mCRC. Methods: GOZILA is a nationwide plasma genomic||

|lorectal cancer (CRC) patients still experience disease recurrence. The early detection of|profiling study using Guardant360 CDx for advanced solid tumors. We assessed ctDNA|profiling study using Guardant360 CDx for advanced solid tumors. We assessed ctDNA|profiling study using Guardant360 CDx for advanced solid tumors. We assessed ctDNA|profiling study using Guardant360 CDx for advanced solid tumors. We assessed ctDNA|profiling study using Guardant360 CDx for advanced solid tumors. We assessed ctDNA||

|molecular residual disease (MRD) has the potential to improve risk assessment.|molecular profile and its association with treatment efficacy in pts with mCRC who were|molecular profile and its association with treatment efficacy in pts with mCRC who were|molecular profile and its association with treatment efficacy in pts with mCRC who were|molecular profile and its association with treatment efficacy in pts with mCRC who were|molecular profile and its association with treatment efficacy in pts with mCRC who were||

|Methods: A total of 104 patients with stage Ⅰ-Ⅳ CRC were enrolled, of which 259 serial|enrolled in GOZILA from January 2018 to July 2022 and underwent ctDNA genotyping|enrolled in GOZILA from January 2018 to July 2022 and underwent ctDNA genotyping|enrolled in GOZILA from January 2018 to July 2022 and underwent ctDNA genotyping|enrolled in GOZILA from January 2018 to July 2022 and underwent ctDNA genotyping|enrolled in GOZILA from January 2018 to July 2022 and underwent ctDNA genotyping||

|plasma samples were collected. Multi-gene targeted sequencing was conducted on|before initiation of first-line systemic tx. ctDNA fraction was defined as the maximum|before initiation of first-line systemic tx. ctDNA fraction was defined as the maximum|before initiation of first-line systemic tx. ctDNA fraction was defined as the maximum|before initiation of first-line systemic tx. ctDNA fraction was defined as the maximum|before initiation of first-line systemic tx. ctDNA fraction was defined as the maximum||

|tumor and plasma samples to identify somatic variants. Results: Among the 104 patients, 14 cases had positive landmark MRD and 32 cases had positive longitudinal MRD. Patients with positive landmark MRD had significantly higher recurrence risk compared to those with negative landmark MRD (Hazard Ratio [HR]: 7.325; 95% CI, 2.877-18.647; P , 0.001). Similarly, positive longitudinal MRD was associated with increased recurrence risk (HR: 9.385; 95% CI: 3.085-28.556; P , 0.001), with a higher HR value. Positive MRD detection preceded CT confirmed recurrence in 85.7% of patients, with a median lead time of 198.5 days. In multivariate analysis, positive-MRD was the most significant prognostic factor for DFS. The combination of KRAS variant and MRD status improved the efficiency of prognostic prediction, the area under the curve value for the combination of MRD and KRAS was higher than MRD and KRAS. By analyzing the characteristic of cfDNA fragments, we found that mutation sites tended to be enriched in shorter cell free DNA (cfDNA) fragments. Conclusions: Our study demonstrated an excellent prognostic prediction potential of circulating tumor DNA-based MRD detection among postoperative CRC patients, especially the combination of KRAS variant and MRD improved the efficiency of risk stratification through MRD. This study may facilitate the incorporation of MRD and KRAS into prognostic prediction. Our study revealed that mutation sites tended to be enriched in shorter DNA fragments, providing valuable insights for future ctDNA detection method. Research Sponsor: Natural Science Foundation of Fujian Province; Natural Science Foundation of Xiamen, China; Medical Innovation Project of Fujian Provincial Health Commission; Xiamen Natural Science Foundation General Project.|variant allelic frequency of somatic alteration and pts were classified into three groups based on ctDNA fraction: low (,1%), middle ($1% and ,10%) and high ($10%) ctDNA fraction groups. Results: This study included 418 pts with mCRC receiving upfront ctDNA genotyping. Median turnaround time of ctDNA test was 7 days, comparable with standard-of-care (SOC) tissue RAS/BRAF testing (7 days) and microsatellite instability (MSI) testing (8 days). Pathogenic alterations were detected in 384 pts (92%), and concordance rates for RAS and BRAF mutation (mut) compared to SOC tissue-based testing were 91% and 97%, respectively. Based on biomarkers identified by ctDNA genotyping, 142 (40%) pts were treated with matched targeted tx: anti-EGFR antibody for RAS/BRAF wild-type (n=137), BRAF inhibitor for BRAF V600E mutation (n=4), and anti-PD-1 antibody for MSI high (n=1). Low, middle, and high ctDNA fraction groups included 87, 97 and 234 pts, respectively, and had significantly different median progression-free survival (PFS) (p,0.01, table) and overall survival (OS) (p,0.01, table), respectively. In 13 pts who repeated ctDNA test before second-line tx, those with elevated ctDNA fraction compared to upfront ctDNA had significantly shorter PFS (median, 3.8 vs. 8.1 months; HR, 5.7, 95% CI, 0.9 to 35.1) and OS (median, 8.2 vs. 17.4 months; HR, 11.3, 95% CI, 1.2 to 105.9) of second-line tx that those with not elevated ctDNA fraction. Conclusions: Upfront ctDNA genotyping successfully identified actionable genomic alterations in pts with mCRC. ctDNA fraction in upfront ctDNA was significantly associated with efficacy of first-line tx and ctDNA fraction monitoring may be useful in determination of subsequent tx. Research Sponsor: SCRUM-Japan Fund. PFS and OS according to ctDNA fraction.|variant allelic frequency of somatic alteration and pts were classified into three groups based on ctDNA fraction: low (,1%), middle ($1% and ,10%) and high ($10%) ctDNA fraction groups. Results: This study included 418 pts with mCRC receiving upfront ctDNA genotyping. Median turnaround time of ctDNA test was 7 days, comparable with standard-of-care (SOC) tissue RAS/BRAF testing (7 days) and microsatellite instability (MSI) testing (8 days). Pathogenic alterations were detected in 384 pts (92%), and concordance rates for RAS and BRAF mutation (mut) compared to SOC tissue-based testing were 91% and 97%, respectively. Based on biomarkers identified by ctDNA genotyping, 142 (40%) pts were treated with matched targeted tx: anti-EGFR antibody for RAS/BRAF wild-type (n=137), BRAF inhibitor for BRAF V600E mutation (n=4), and anti-PD-1 antibody for MSI high (n=1). Low, middle, and high ctDNA fraction groups included 87, 97 and 234 pts, respectively, and had significantly different median progression-free survival (PFS) (p,0.01, table) and overall survival (OS) (p,0.01, table), respectively. In 13 pts who repeated ctDNA test before second-line tx, those with elevated ctDNA fraction compared to upfront ctDNA had significantly shorter PFS (median, 3.8 vs. 8.1 months; HR, 5.7, 95% CI, 0.9 to 35.1) and OS (median, 8.2 vs. 17.4 months; HR, 11.3, 95% CI, 1.2 to 105.9) of second-line tx that those with not elevated ctDNA fraction. Conclusions: Upfront ctDNA genotyping successfully identified actionable genomic alterations in pts with mCRC. ctDNA fraction in upfront ctDNA was significantly associated with efficacy of first-line tx and ctDNA fraction monitoring may be useful in determination of subsequent tx. Research Sponsor: SCRUM-Japan Fund. PFS and OS according to ctDNA fraction.|variant allelic frequency of somatic alteration and pts were classified into three groups based on ctDNA fraction: low (,1%), middle ($1% and ,10%) and high ($10%) ctDNA fraction groups. Results: This study included 418 pts with mCRC receiving upfront ctDNA genotyping. Median turnaround time of ctDNA test was 7 days, comparable with standard-of-care (SOC) tissue RAS/BRAF testing (7 days) and microsatellite instability (MSI) testing (8 days). Pathogenic alterations were detected in 384 pts (92%), and concordance rates for RAS and BRAF mutation (mut) compared to SOC tissue-based testing were 91% and 97%, respectively. Based on biomarkers identified by ctDNA genotyping, 142 (40%) pts were treated with matched targeted tx: anti-EGFR antibody for RAS/BRAF wild-type (n=137), BRAF inhibitor for BRAF V600E mutation (n=4), and anti-PD-1 antibody for MSI high (n=1). Low, middle, and high ctDNA fraction groups included 87, 97 and 234 pts, respectively, and had significantly different median progression-free survival (PFS) (p,0.01, table) and overall survival (OS) (p,0.01, table), respectively. In 13 pts who repeated ctDNA test before second-line tx, those with elevated ctDNA fraction compared to upfront ctDNA had significantly shorter PFS (median, 3.8 vs. 8.1 months; HR, 5.7, 95% CI, 0.9 to 35.1) and OS (median, 8.2 vs. 17.4 months; HR, 11.3, 95% CI, 1.2 to 105.9) of second-line tx that those with not elevated ctDNA fraction. Conclusions: Upfront ctDNA genotyping successfully identified actionable genomic alterations in pts with mCRC. ctDNA fraction in upfront ctDNA was significantly associated with efficacy of first-line tx and ctDNA fraction monitoring may be useful in determination of subsequent tx. Research Sponsor: SCRUM-Japan Fund. PFS and OS according to ctDNA fraction.|variant allelic frequency of somatic alteration and pts were classified into three groups based on ctDNA fraction: low (,1%), middle ($1% and ,10%) and high ($10%) ctDNA fraction groups. Results: This study included 418 pts with mCRC receiving upfront ctDNA genotyping. Median turnaround time of ctDNA test was 7 days, comparable with standard-of-care (SOC) tissue RAS/BRAF testing (7 days) and microsatellite instability (MSI) testing (8 days). Pathogenic alterations were detected in 384 pts (92%), and concordance rates for RAS and BRAF mutation (mut) compared to SOC tissue-based testing were 91% and 97%, respectively. Based on biomarkers identified by ctDNA genotyping, 142 (40%) pts were treated with matched targeted tx: anti-EGFR antibody for RAS/BRAF wild-type (n=137), BRAF inhibitor for BRAF V600E mutation (n=4), and anti-PD-1 antibody for MSI high (n=1). Low, middle, and high ctDNA fraction groups included 87, 97 and 234 pts, respectively, and had significantly different median progression-free survival (PFS) (p,0.01, table) and overall survival (OS) (p,0.01, table), respectively. In 13 pts who repeated ctDNA test before second-line tx, those with elevated ctDNA fraction compared to upfront ctDNA had significantly shorter PFS (median, 3.8 vs. 8.1 months; HR, 5.7, 95% CI, 0.9 to 35.1) and OS (median, 8.2 vs. 17.4 months; HR, 11.3, 95% CI, 1.2 to 105.9) of second-line tx that those with not elevated ctDNA fraction. Conclusions: Upfront ctDNA genotyping successfully identified actionable genomic alterations in pts with mCRC. ctDNA fraction in upfront ctDNA was significantly associated with efficacy of first-line tx and ctDNA fraction monitoring may be useful in determination of subsequent tx. Research Sponsor: SCRUM-Japan Fund. PFS and OS according to ctDNA fraction.|variant allelic frequency of somatic alteration and pts were classified into three groups based on ctDNA fraction: low (,1%), middle ($1% and ,10%) and high ($10%) ctDNA fraction groups. Results: This study included 418 pts with mCRC receiving upfront ctDNA genotyping. Median turnaround time of ctDNA test was 7 days, comparable with standard-of-care (SOC) tissue RAS/BRAF testing (7 days) and microsatellite instability (MSI) testing (8 days). Pathogenic alterations were detected in 384 pts (92%), and concordance rates for RAS and BRAF mutation (mut) compared to SOC tissue-based testing were 91% and 97%, respectively. Based on biomarkers identified by ctDNA genotyping, 142 (40%) pts were treated with matched targeted tx: anti-EGFR antibody for RAS/BRAF wild-type (n=137), BRAF inhibitor for BRAF V600E mutation (n=4), and anti-PD-1 antibody for MSI high (n=1). Low, middle, and high ctDNA fraction groups included 87, 97 and 234 pts, respectively, and had significantly different median progression-free survival (PFS) (p,0.01, table) and overall survival (OS) (p,0.01, table), respectively. In 13 pts who repeated ctDNA test before second-line tx, those with elevated ctDNA fraction compared to upfront ctDNA had significantly shorter PFS (median, 3.8 vs. 8.1 months; HR, 5.7, 95% CI, 0.9 to 35.1) and OS (median, 8.2 vs. 17.4 months; HR, 11.3, 95% CI, 1.2 to 105.9) of second-line tx that those with not elevated ctDNA fraction. Conclusions: Upfront ctDNA genotyping successfully identified actionable genomic alterations in pts with mCRC. ctDNA fraction in upfront ctDNA was significantly associated with efficacy of first-line tx and ctDNA fraction monitoring may be useful in determination of subsequent tx. Research Sponsor: SCRUM-Japan Fund. PFS and OS according to ctDNA fraction.||

|||||HR|HR||

|||Group|Median PFS (months)|(95% CI)|2-yr OS rate|(95% CI)|

|||Low|22.1|Ref|82.7%|Ref|

|||Middle|14.5|1.5|64.1%|1.8|

|||||(0.9-2.3)|(1.0-3.2)||

|||High|8.8|2.7|49.4%|3.2|

|||||(1.8-3.9)|(1.9-5.3)||

|158|Poster Session||||||

|Clinical utility of serial circulating tumor DNA (ctDNA) to identify acquired|||||||

|resistance to anti-EGFR antibodies in metastatic colorectal cancer (mCRC).|||||||

|First Author: Jonathan M. Loree, BCCA, Vancouver Cancer Centre, Vancouver, BC,|||||||

|Canada|||||||

|Background: Real-world evidence informing on the value of incorporating serial ctDNA|||||||

|into clinical practice is lacking. We aimed to explore the utility of serial ctDNA for|||||||

|identifying mechanisms of resistance and new targets for patients (pts) receiving anti-|||||||

|EGFR therapy for mCRC. Methods: We retrospectively reviewed 2801 pts with mCRC|||||||

|who had $1 alteration detected on a Guardant360 assay (Guardant Health) and|||||||

|subsequently had serial ctDNA assessments with known intervening therapies. We|||||||

|compared detection of new MAPK pathway alterations (RAS/EGFR/BRAFV600 SNV or|||||||

|indel, MET or ERBB2 amplification) among patients who initially lacked these alterations|||||||

|by whether patients received anti-EGFR antibody alone (panitumumab or cetuximab), in|||||||

|combination with chemotherapy, or if they had never received an anti-EGFR antibody|||||||

|retrospectively reviewed patients with ESCC who received neoadjuvant DCF therapy and|

|R0 resection between Feb 2014 to June 2022 in our hospital. We evaluated histo-|

|pathological response by neoadjuvant DCF therapy based on the Japanese Classification|

|of Esophageal Cancer 12 th (Grade 0: ineffective, Grade 1: slightly effective, Grade 2:|

|moderately effective, Grade 3: markedly effective [pT0]) and objective response rate|

|(ORR), progression-free survival (PFS) during platinum-containing regimens as clinical|

|efficacy outcomes. We analyzed the correlation between histopathological response and|

|ORR, PFS using Fisher's exact tests and the log-rank tests. In addition, we analyzed|

|clinical factors related to clinical efficacy of palliative chemotherapy using Cox pro-|

|statistical difference (p = 0.696). The median PFS was 2.43 (95%CI: 2.33-2.53) months in|

|histopathological response 0/1 group and 4.04 (95%CI: 0-10.77) months in histo-|

|pathological 2/3 group (HR[95%CI|

|Conclusions: T-||

|Patients were divided into early (EA)-and late (LA)-nivolumab infusion groups: EA group = $70% of their infusions before 14:00, and LA group = ,70% of their infusions before 14:00. Treatment efficacy (overall response rate [ORR], disease control rate [DCR] , progression-free survival [PFS], and overall survival [OS] ) was evaluated. Multivariate analyses included variables with P values ,0.1 in univariate analyses. Results: A total of 248 patients were eligible; 140 were classified as having EA, and 108 as having LA. Most baseline characteristics were similar between EA and LA. In contrast, the median infusion time was earlier in EA than in LA (11:50 vs. 14:22). The median follow-up time was 9.0 months (range, 1.2-64.7 months). ORR and DCR were significantly higher in the EA than in the LA among 149 patients with measurable lesions (ORR, 16.9% vs. 3.3%, P=0.01; DCR, 47.2% vs. 20.0%, P,0.01). Patients with EA had significantly better prognoses than those with LA in terms of PFS (median PFS, 2.3 vs. 1.6 months.; hazard ratios [HR], 0.65; P,0.01) and OS (median OS, 7.6 vs. 3.9 months.; HR, 0.64; P,0.01). EA patients received the subsequent chemotherapy more frequently than those in LA (54% vs. 32%; P,0.01). 269 Additionally, surrogacy between each short-term postoperative endpoint (pathological Poster Session complete response [pCR] or pathological grade) and OS was investigated using novel statistical methods. Results: Our study encompassed 3154 ESCC patients who un-derwent subtotal esophagectomy from 2010 to 2015. The cStage I/II/III/IVA/IVB (due to supraclavicular lymph node metastasis) was 224 (7.1%), 1008 (32.0%), 1664 (52.8%), 117 (3.7%), and 140 (4.4%), respectively. The 5-year OS and RFS rate for the entire cohort was 56.6% and 47.7%, respectively. In the primary analysis, a strong correlation between RFS and OS was found (Kendall's tau = 0.797, 95% confidence interval [CI]: 0.782 to 0.812) at the individual level. Subgroup analysis revealed that the better the pathological response, the higher the tau value. An adjusted R 2 of 100.0% (95% CI: 40.2 to 100.0) was|Patients were divided into early (EA)-and late (LA)-nivolumab infusion groups: EA group = $70% of their infusions before 14:00, and LA group = ,70% of their infusions before 14:00. Treatment efficacy (overall response rate [ORR], disease control rate [DCR] , progression-free survival [PFS], and overall survival [OS] ) was evaluated. Multivariate analyses included variables with P values ,0.1 in univariate analyses. Results: A total of 248 patients were eligible; 140 were classified as having EA, and 108 as having LA. Most baseline characteristics were similar between EA and LA. In contrast, the median infusion time was earlier in EA than in LA (11:50 vs. 14:22). The median follow-up time was 9.0 months (range, 1.2-64.7 months). ORR and DCR were significantly higher in the EA than in the LA among 149 patients with measurable lesions (ORR, 16.9% vs. 3.3%, P=0.01; DCR, 47.2% vs. 20.0%, P,0.01). Patients with EA had significantly better prognoses than those with LA in terms of PFS (median PFS, 2.3 vs. 1.6 months.; hazard ratios [HR], 0.65; P,0.01) and OS (median OS, 7.6 vs. 3.9 months.; HR, 0.64; P,0.01). EA patients received the subsequent chemotherapy more frequently than those in LA (54% vs. 32%; P,0.01). 269 Additionally, surrogacy between each short-term postoperative endpoint (pathological Poster Session complete response [pCR] or pathological grade) and OS was investigated using novel statistical methods. Results: Our study encompassed 3154 ESCC patients who un-derwent subtotal esophagectomy from 2010 to 2015. The cStage I/II/III/IVA/IVB (due to supraclavicular lymph node metastasis) was 224 (7.1%), 1008 (32.0%), 1664 (52.8%), 117 (3.7%), and 140 (4.4%), respectively. The 5-year OS and RFS rate for the entire cohort was 56.6% and 47.7%, respectively. In the primary analysis, a strong correlation between RFS and OS was found (Kendall's tau = 0.797, 95% confidence interval [CI]: 0.782 to 0.812) at the individual level. Subgroup analysis revealed that the better the pathological response, the higher the tau value. An adjusted R 2 of 100.0% (95% CI: 40.2 to 100.0) was||| |---|---|---|---|

|270|Poster Session|271|Poster Session|

|||groups were as follows, respectively: median age 65.0 and 59.5 years (p = 0.02); PS 0,|groups were as follows, respectively: median age 65.0 and 59.5 years (p = 0.02); PS 0,|

|||16.1% and 26.7% (p = 0.06); diffuse histology, 52.7% and 26.7% (p , 0.01); lymph node|16.1% and 26.7% (p = 0.06); diffuse histology, 52.7% and 26.7% (p , 0.01); lymph node|

|Results: Sixty-seven patients (3 treated with chemoradiotherapy alone, 15 with sys-|95%CI 8.2-24.7, p=0.0103, HR 0.01), lower alcalin phosphatase (ALP; ,136 U/l;|95%CI 8.2-24.7, p=0.0103, HR 0.01), lower alcalin phosphatase (ALP; ,136 U/l;||||||||

|temic therapy alone and 49 with total neoadjuvant therapy) were identified. Positive|p=0.0001, HR=0.0001; 95%CI 12-39.5 vs 95% CI 8.2-10.4), lactate dehydrogenasis|p=0.0001, HR=0.0001; 95%CI 12-39.5 vs 95% CI 8.2-10.4), lactate dehydrogenasis||||||||

|ctDNA was identified in 6 (8.9%) within 3 months after resection, all of whom received|(LDH; ,365 U/l; p,0,0001, HR=0.0000006; 95%CI 24.7-39.5 vs 95% CI 8.2-10.4) and|(LDH; ,365 U/l; p,0,0001, HR=0.0000006; 95%CI 24.7-39.5 vs 95% CI 8.2-10.4) and||||||||

|total neoadjuvant therapy, and 3/6 recurred within 12 months. Clinical T status|platelet to lymphocyte ratio (PLR; #253; p,0.0001, HR= 0.00000062; 95%CI 24.7-39.5|platelet to lymphocyte ratio (PLR; #253; p,0.0001, HR= 0.00000062; 95%CI 24.7-39.5||||||||

|(p=0.146), N status (p=0.842), mrEMVI (p=0.475) and PSW (p=0.318) were not asso-|vs 95% CI 8.2-10.4). Median PFS was 14.9 m (95% CI 9.5-18.5). The same factors were|vs 95% CI 8.2-10.4). Median PFS was 14.9 m (95% CI 9.5-18.5). The same factors were||||||||

|ciated with MRD. TRG was not associated with MRD (TRG0-1: 4% vs TRG2-3: 11.3%,|significantly related to PFS, which was 18.3 m vs 2.7 m for higher monocyte count (95%|significantly related to PFS, which was 18.3 m vs 2.7 m for higher monocyte count (95%||||||||

|204 CI 11.207 p=0.547). Pathologic N status was associated with MRD (ypN0: 4.4% vs ypN+: 18%, p=0.049). MRD was associated with a median RFS of 3.2 months (HR 39, 95% CI: 4.1-380, p=0.0015). 1-year RFS was 98% for patients without MRD. Conclusions: Minimal residual disease after multi-modality treatment of LARC is associated with early metastatic recurrence. The patient informed MRD assay appears both sensitive and specific for detection of relapse. Advanced clinical stage and high-risk radiologic features were not associated with MRD, while post-treatment pathologic N status was. Given the high relapse rate for MRD+ patients, MRD detection after resection warrants additional investigation for metastases and/or enrollment on MRD treatment clinical trial. Methods to predict MRD prior to resection are urgently needed. Research Sponsor: None. Poster Session 208|Poster Session Poster Session|||||||||

|||||||||Prediction of resistance to bevacizumab plus FOLFOX in metastatic colo-|Prediction of resistance to bevacizumab plus FOLFOX in metastatic colo-|

|||||||||rectal cancer using a multi-marker panel and a machine-learning approach:|rectal cancer using a multi-marker panel and a machine-learning approach:|

|||||||||Final results of the prospective multicenter PERMAD trial. First Author: Hans A.|Final results of the prospective multicenter PERMAD trial. First Author: Hans A.|

|||||||||Kestler, Ulm University -Institute of Medical Systems Biology, Ulm, Germany|Kestler, Ulm University -Institute of Medical Systems Biology, Ulm, Germany|

|||||||||Background: Anti-vascular endothelial growth factor (VEGF) monoclonal antibodies|Background: Anti-vascular endothelial growth factor (VEGF) monoclonal antibodies|

|||||||||(mAbs) are widely used for tumor treatment, including metastatic colorectal cancer|(mAbs) are widely used for tumor treatment, including metastatic colorectal cancer|

|||||||||(mCRC). So far, there are no biomarkers that reliably predict resistance to anti-VEGF|(mCRC). So far, there are no biomarkers that reliably predict resistance to anti-VEGF|

|||||||||mAbs like bevacizumab. A biomarker-guided strategy for early and accurate assessment|mAbs like bevacizumab. A biomarker-guided strategy for early and accurate assessment|

|||||||||of resistance could avoid the use of non-effective treatment and improve patient|of resistance could avoid the use of non-effective treatment and improve patient|

|||||||||outcomes. We hypothesized that repeated analysis of multiple cytokines and angiogenic|outcomes. We hypothesized that repeated analysis of multiple cytokines and angiogenic|

|||||||||growth factors (CAFs) before and during treatment using machine learning could provide|growth factors (CAFs) before and during treatment using machine learning could provide|

|||||||||an accurate and earlier, i.e., 100 days before conventional radiologic staging, prediction|an accurate and earlier, i.e., 100 days before conventional radiologic staging, prediction|

|||||||||of resistance to first-line mCRC treatment with FOLFOX plus bevacizumab. Methods: 15|of resistance to first-line mCRC treatment with FOLFOX plus bevacizumab. Methods: 15|

|||||||||German and Austrian centers prospectively recruited 154 mCRC patients receiving|German and Austrian centers prospectively recruited 154 mCRC patients receiving|

|||||||||FOLFOX plus bevacizumab as first-line treatment. Plasma samples were collected every|FOLFOX plus bevacizumab as first-line treatment. Plasma samples were collected every|

|||||||||two weeks until radiologic progression (RECIST 1.1) as determined by CT scans per-|two weeks until radiologic progression (RECIST 1.1) as determined by CT scans per-|

|||||||||formed every 2 months. 102 pre-selected CAFs were centrally analyzed using a cytokine|formed every 2 months. 102 pre-selected CAFs were centrally analyzed using a cytokine|

|||||||||multiplex assay (Luminex, Myriad RBM). Results: Using random forest machine|multiplex assay (Luminex, Myriad RBM). Results: Using random forest machine|

|||||||||learning, we developed a predictive model that discriminated between the situations of|learning, we developed a predictive model that discriminated between the situations of|

|||||||||"no progress within 100 days before radiological progress" and "progress within|"no progress within 100 days before radiological progress" and "progress within|

|||||||||100 days before radiological progress". Into this we incorporated a combination of ten|100 days before radiological progress". Into this we incorporated a combination of ten|

|||||||||out of the 102 CAF markers, which fulfilled this task with 81% accuracy, 72% sensitivity,|out of the 102 CAF markers, which fulfilled this task with 81% accuracy, 72% sensitivity,|

|||||||||and 88% specificity. Conclusions: Using artificial intelligence we identified a CAF|and 88% specificity. Conclusions: Using artificial intelligence we identified a CAF|

|||||||||marker combination that indicates treatment resistance to FOLFOX plus bevacizumab in|marker combination that indicates treatment resistance to FOLFOX plus bevacizumab in|

|||||||||patients with mCRC within 100 days prior to radiologic progress. Further studies are|patients with mCRC within 100 days prior to radiologic progress. Further studies are|

|Adjusted outcome analyses.|||||||required to show its clinical value. Clinical trial information: NCT02331927. Research|required to show its clinical value. Clinical trial information: NCT02331927. Research||

|||Chemo + EGFR mAb (n=244) HR (95% CI)|||Chemo + bev (n=1865) HR (95% CI)|Sponsor: Sanofi Aventis.||||

||Prevalence (%)|rwPFS||rwOS|||rwPFS|rwOS||

|Right vs. Left side|33.2 vs. 66.8|1.67 (1.19-2.37)|1.87 (1.21-2.89)||1.09 (0.98-1.20)|1.23 (1.09-1.40)||||

|p=0.003 Median survival on EGFRi (days) among the CTX-S quintiles (lowest to highest scores). p=0.005 p=0.097 p,0.001 Biomarker (+) vs. (-)||||||||||

|Groups/Quintiles RASalt|1 st 12.6|2 nd 2.83 (1.80-4.45) p,0.001|3 rd 3.58 (2.09-6.15) p,0.001|4 th|5 th 1.26 (1.09-1.46) p,0.001|1.65 (1.40-1.95) p-value p,0.001||||

|RAS WT /BRAF WT APCalt RAS MUT /BRAF MUT Left-sided RAS/APCalt|384 32.0 396 378 50.3|428 0.55 (0.41-0.73) 329 p,0.001 441 1.31 (0.88-1.96) p=0.178|825 0.39 (0.27-0.57) 966 631 638 p,0.009 798 921 1.83 (1.13-2.97) p=0.014|898 0.81 (0.72-0.90) 1210 p,0.001 898 1.07 (0.97-1.18) p=0.198|0.63 (0.55-0.72) 0.0 p,0.001 7e-05 1.07 (0.95-1.21) 0.0 p,0.001|||||

|Right-sided None|282 5.0|231 1.37 (0.88-2.14)|631 1.45 (0.80-2.64) 854|1014 1.07 (0.85-1.35)|0.0 1.69 (1.30-2.20)|||||

|Non-CMS2|395|413 p=0.002|665|p=0.223|854|935 p,0.001|0.0 p,0.001|||

|215|Poster Session| |---|---|

||N = 1,799| |---|---|

|Age, Median (IQR)|66 (57, 74)|

|Year of diagnosis, n (%)||

|2017|437 (24%)|

|2018|330 (18%)|

|2019|317 (18%)|

|2020|364 (20%)|

|2021|351 (20%)|

|eGFR < 30, n (%)|18 (1.0%)|

|Sex, n (%)||

|Male|974 (54%)|

|Female|825 (46%)|

|Patients|390|Percentage| |---|---|---|

|Age|||

|Mean|72||

|Range|35 -95||

|Sex|||

|Male|213|55%|

|Female|177|45%|

|Location|||

|Right|197|51%|

|Left|193|49%|

|T|||

|1|2|1 %|

|2|15|4%|

|3|209|53%|

|4|163|42%|

|Grade|||

|1|13|3%|

|2|334|88%|

|3|32|8%|

|Lymph node|||

|> = 12|342|89%|

|< = 12|44|11%|

|Obstruction|||

|No|346|89%|

|Yes|44|11%|

|Perforation|||

|No|358|92%|

|Yes|32|8%|

|LVI|||

|No|206|53%|

|Yes|184|47%|

|PNI|||

|No|303|78%|

|Yes|87|22%|

|Adyuvance|||

|Yes|197|51%|

|No|192|49%|

|MMR|||

|MSS|316|81%|

|MSI|55|14%|

|Unknown|19|5%|

|R|||

|0|363|93%|

|1|27|7%|

|Pre-surgery CEA|||

|Mean|7,4||

|Range|0,5 -150||

|Key efficacy endpoints.||| |---|---|---|

||Tira + Atezo + CT|Placebo + CT|

||(n=229)|(n=232)|

|OS: median, mo*|15.7|11.1|

|Stratified HR (95% CI); P value IRF-assessed PFS: median, mo †|0.70 (0.55, 0.88); 0.0024 6.2|5.4|

|Stratified HR (95% CI); P value INV-assessed PFS: median, mo †|0.56 (0.45, 0.70); ,0.0001 7.0|5.5|

|Stratified HR (95% CI) IRF-assessed ORR, † % Median IRF-assessed DoR, † mo|0.57 (0.46, 0.72) 59.7 7.1|45.5 4.3|

|||||251|Rapid Oral Abstract Session| |---|---|---|---|---|---|

|||||ESCC and||

||ITT|ESCC|CPS ‡10|CPS ‡10||

|OS and PFS|n = 749|n = 548|n = 383|n = 286||

|OS, median, HR (95% CI) a,b 5-yr OS rate, a,b|0.72 (0.62-0.84) 10.6 vs 3.0|0.71 (0.60-0.85) 11.8 vs 3.4|0.64 (0.52-0.80) 12.8 vs 3.8|0.60 (0.46-0.76) 13.8 vs 3.7||

|%||||||

|PFS, median,||||||

|HR (95% CI)||||||

|||||||253|Poster Session|| |---|---|---|---|---|---|---|---|---|

|||Median OS|Unstratified||Median OS|Unstratified|||

||n|NIVO + chemo Chemo|HR (95% CI)|n|NIVO + IPI Chemo|NIVO + IPI Chemo|NIVO + IPI Chemo|NIVO + IPI Chemo|

|All TMB-evaluable 381|14.4|10.1 0.80 (0.64, 1.00) 390|15.1|10.1 0.75 (0.60, 0.95)|||||

|TMB-high|32|23.8|13.1 0.67 (0.28, 1.63) 22|15.7|13.1 1.20 (0.46, 3.14)||||

|TMB-low|349|14.0|10.2 0.80 (0.66, 1.05) 368|15.1|10.2 0.73 (0.58, 0.93)||||

|All GES-evaluable 383|15.5|9.5 0.75 (0.60, 0.94) 380|13.9|9.5 0.72 (0.57, 0.91)|||||

|Inflammatory|||||||||

|High|128|22.0|12.6 0.63 (0.41, 0.96) 127|23.1|12.1 0.58 (0.37, 0.90)||||

|Med|127|12.5|8.6 0.68 (0.46, 0.98) 126|16.2|8.6 0.59 (0.40, 0.87)||||

|Low|128|13.4|9.6 0.98 (0.66, 1.43) 127|9.7|9.6 1.05 (0.71, 1.54)||||

|b-catenin|||||||||

|High|128|11.1|9.9 1.05 (0.72, 1.54) 127|13.5|9.9 0.73 (0.49, 1.08)||||

|Med|127|19.1|10.2 0.64 (0.42, 0.97) 126|10.9|10.7 0.97 (0.65, 1.44)||||

|Low|128|15.8|9.1 0.60 (0.41, 0.89) 127|18.3|9.1 0.50 (0.33, 0.76)||||

|Fibroblast|||||||||

|High|128|14.0|11.9 0.84 (0.57, 1.24) 127|11.3|11.7 0.98 (0.65, 1.46)||||

|Med|127|15.7|8.8 0.64 (0.43, 0.95) 126|17.2|8.6 0.56 (0.37, 0.85)||||

|Low|128|15.8|9.4 0.76 (0.51, 1.12) 127|19.3|9.3 0.70 (0.47, 1.05)||||

|254||||||Poster Session|255|Poster Session|

||||Group 1|Group 2|Group 3|Group 3|Group 3|Group 3|

||||(age 18-44)|(age 45-64)|(age 65+)|(age 65+)|(age 65+)|(age 65+)|

|Total # gastric cancer||5785|28370|43590|||||

|Ethnicity:|||||||||

|White|||29.39%|46.70%|56.04%|56.04%|56.04%|56.04%|

|Black|||14.52%|17.38%|15.12%|15.12%|15.12%|15.12%|

|Hispanic|||34.31%|19.74%|12.88%|12.88%|12.88%|12.88%|

|Asian or Pacific Islander|21.78%|16.18%|15.96%|15.96%|15.96%|15.96%|15.96%|15.96%|

|Risk factor predominance in Hispanics|||P Value||||||

|Helicobacter pylori||8.56%|3.57%||2.14%|0.00|||

|Smoker|||19.9%|28.12%|31.08%|31.08%|31.08%|31.08%|

|Diabetes Mellitus|||3.02%|4.29%||2.32%|0.00||

|Alcohol use|||8.06%|26.43%|35.98%|35.98%|35.98%|35.98%|

|Gastric ulcer|||11.59%|9.46%||10.69%|10.69%|10.69%|

|Gastric polyp|||0.50%|0.63%||1.51%|0.1488||

|Obesity|||8.31%|6.88%||9.08%0|9.08%0|9.08%0|

||||||||257||||Poster Session| |---|---|---|---|---|---|---|---|---|---|---|---|

||All Race|White|African-American|Hispanics|Asian|Native American/Other|Variable||n=|Hazard Ratio|Hazard Ratio|

|Mortality Rate Mean LOS Total Charge Cancer presentation Local Gastroin-testinal involvement Chemotherapy Lymph node|7.4% 7.360.1 $87,787.86980.7 $84945.0361171.2 $81425.776 7.9% 7.2% 7.160.1 7.960.1 1366.6 33.4% 31.5% 33.9% 22.1% 22.5% 18.3% 13.1% 13.1% 11.5%|7.2% 7.260.1 $96,696.961,874.9 $101,436.863,253.5 $93102.763954.7 8.0% 9.2% 7.260.2 7.560.2 37.5% 34.9% 37.9% 24.1% 22.4% 22.7% 13.5% 13.9% 14.6%|Age < 50 50-65 ‡ 65 Treatment nCRT + esophagectomy dCRT RT alone|2918 15948 19009 16838 19895 1142|Reference 1.08 (1.02, 1.13) 1.18 (1.12, 1.24) Reference 1.91 (1.86, 1.96) 2.75 (2.58, 2.94)|Reference 1.08 (1.02, 1.13) 1.18 (1.12, 1.24) Reference 1.91 (1.86, 1.96) 2.75 (2.58, 2.94)|Reference 1.08 (1.02, 1.13) 1.18 (1.12, 1.24) Reference 1.91 (1.86, 1.96) 2.75 (2.58, 2.94)|Reference 1.08 (1.02, 1.13) 1.18 (1.12, 1.24) Reference 1.91 (1.86, 1.96) 2.75 (2.58, 2.94)|Reference 1.08 (1.02, 1.13) 1.18 (1.12, 1.24) Reference 1.91 (1.86, 1.96) 2.75 (2.58, 2.94)|Reference 1.08 (1.02, 1.13) 1.18 (1.12, 1.24) Reference 1.91 (1.86, 1.96) 2.75 (2.58, 2.94)|Reference 1.08 (1.02, 1.13) 1.18 (1.12, 1.24) Reference 1.91 (1.86, 1.96) 2.75 (2.58, 2.94)|

|involvement Spread to non-GI organs|19.4%|19.8%|18.5%|19.5%|18.4%|20.4%|Race White Black|32140 3236 1194|Reference 1.10 (1.06, 1.15) 0.82 (0.76, 0.88)|Reference 1.10 (1.06, 1.15) 0.82 (0.76, 0.88)|Reference 1.10 (1.06, 1.15) 0.82 (0.76, 0.88)|

||||||||Hispanic||826|0.77 (0.70, 0.84)|0.77 (0.70, 0.84)|

||||||||East Asian, South Asian, Pacific Islander|479|0.87 (0.78, 0.97)|0.87 (0.78, 0.97)|0.87 (0.78, 0.97)|

|258|||||Poster Session|||||||

||||||||Primary Outcomes|Solid Cancer Gastric Cancer|P value|||

||||||||Total|77,674||710||

||||||||Mortality|3,175 (4.1%)|65 (9.2%) aOR= 2.04; P= 0.034|65 (9.2%) aOR= 2.04; P= 0.034|65 (9.2%) aOR= 2.04; P= 0.034|

||||||||Mean Length of Stay (Days)|7.8||8.9|P= 0.11|

||||||||Mean Total Hospital Charge (USD)|96,074|115,805|P= 0.246||

|265|Poster Session| |---|---|

|Results: Overall, 58 patients (median age, 64 years; 69% male) were eligible (T-DXd|Results: Overall, 58 patients (median age, 64 years; 69% male) were eligible (T-DXd|

|group, n = 20; nivolumab group, n = 38). Most had HER2 3+ (72%) and presented with|group, n = 20; nivolumab group, n = 38). Most had HER2 3+ (72%) and presented with|

|metastatic disease at diagnosis (66%). Response rates in the 41 patients with mea-|metastatic disease at diagnosis (66%). Response rates in the 41 patients with mea-|

|surable lesions were 50% and 15% in the T-DXd and nivolumab groups, respectively. The|surable lesions were 50% and 15% in the T-DXd and nivolumab groups, respectively. The|

|T-DXd and nivolumab groups had a median progression-free survival of 4.8 months (95%|T-DXd and nivolumab groups had a median progression-free survival of 4.8 months (95%|

|confidence interval [CI], 3.3-7.0) and 2.3 months (95% CI, 1.5-3.5), median overall|confidence interval [CI], 3.3-7.0) and 2.3 months (95% CI, 1.5-3.5), median overall|

|survival of 10.8 months (95% CI, 6.9-23.8) and 11.7 months (95% CI, 7.6-17.1), and|survival of 10.8 months (95% CI, 6.9-23.8) and 11.7 months (95% CI, 7.6-17.1), and|

|grade 3 or greater adverse event rates of 50% and 2%, respectively. Overall, 64% received|grade 3 or greater adverse event rates of 50% and 2%, respectively. Overall, 64% received|

|subsequent treatment. Among 23 patients who received both regimens, the T-DXd-|subsequent treatment. Among 23 patients who received both regimens, the T-DXd-|

|nivolumab and nivolumab-T-DXd groups had a median overall survival of 14.0 months|nivolumab and nivolumab-T-DXd groups had a median overall survival of 14.0 months|

|(95% CI, 5.0-not reached) and 19.3 months (95% CI, 9.5-25.1), respectively.|(95% CI, 5.0-not reached) and 19.3 months (95% CI, 9.5-25.1), respectively.|

|||obtained with the meta-regression model at the institutional level. The surrogate|obtained with the meta-regression model at the institutional level. The surrogate|

|||threshold effect was 0.703. Tau between pCR or pathological grade and OS were -0.025|threshold effect was 0.703. Tau between pCR or pathological grade and OS were -0.025|

|||(95% CI: -0.335 to 0.285) and 0.062 (95% CI: -0.086 to 0.209), respectively.|(95% CI: -0.335 to 0.285) and 0.062 (95% CI: -0.086 to 0.209), respectively.|

|||35.9% and 33.3%; PS 1, 57.5% and 65.0%; PS 2, 6.5% and 1.7% (p = 0.28); HER2 positive,|35.9% and 33.3%; PS 1, 57.5% and 65.0%; PS 2, 6.5% and 1.7% (p = 0.28); HER2 positive,|

||Large|metastasis, 74.0% and 93.3% (p , 0.01); peritoneal metastasis, 66.4% and 25.0% (p ,|metastasis, 74.0% and 93.3% (p , 0.01); peritoneal metastasis, 66.4% and 25.0% (p ,|

|type 3($8cm) and type 4 were found in 18 cases. The median tumor size was 50 (10-|type 3($8cm) and type 4 were found in 18 cases. The median tumor size was 50 (10-|0.01); liver metastasis, 26.4% and 40.0% (p = 0.03); lung metastasis, 6.5% and 16.7%|0.01); liver metastasis, 26.4% and 40.0% (p = 0.03); lung metastasis, 6.5% and 16.7%|

|232) mm. The depth of invasion was cT1 in 31 patients, cT2 in 19, cT3 in 11, cT4a in 28,|232) mm. The depth of invasion was cT1 in 31 patients, cT2 in 19, cT3 in 11, cT4a in 28,|(p , 0.01). The proportions of fluoropyrimidine, taxanes, and irinotecan in all treatment|(p , 0.01). The proportions of fluoropyrimidine, taxanes, and irinotecan in all treatment|

|and cT4b in 10. Histology was differentiated type in 46 patients and undifferentiated|and cT4b in 10. Histology was differentiated type in 46 patients and undifferentiated|lines did not differ between the two groups (fluoropyrimidine, 99.7% vs. 100%; taxanes,|lines did not differ between the two groups (fluoropyrimidine, 99.7% vs. 100%; taxanes,|

|type in 56. Completion gastrectomy was performed in 98 patients and partial gas-|type in 56. Completion gastrectomy was performed in 98 patients and partial gas-|70.1% vs. 73.3%; irinotecan, 23.0% vs. 23.3%). However, the EGJA group used ramu-|70.1% vs. 73.3%; irinotecan, 23.0% vs. 23.3%). However, the EGJA group used ramu-|

|trectomy in 1. 89 patients underwent splenectomy. The univariate analysis showed that|trectomy in 1. 89 patients underwent splenectomy. The univariate analysis showed that|cirumab, trastuzumab, and immune checkpoint inhibitors (ICIs) significantly more|cirumab, trastuzumab, and immune checkpoint inhibitors (ICIs) significantly more|

|tumor location (lesser curvature vs others, p=0.027) and depth of invasion (cT1-3 vs cT4,|tumor location (lesser curvature vs others, p=0.027) and depth of invasion (cT1-3 vs cT4,|frequently than the GA group (ramucirumab, 27.8% vs. 43.3%, p = 0.02; trastuzumab,|frequently than the GA group (ramucirumab, 27.8% vs. 43.3%, p = 0.02; trastuzumab,|

|p=0.032) were significant risk factors for #10 nodal metastasis. By multivariate analysis,|p=0.032) were significant risk factors for #10 nodal metastasis. By multivariate analysis,|15.4% vs. 26.7%, p = 0.03; ICIs, 21.0% vs. 41.7%, p , 0.01). Overall survival did not differ|15.4% vs. 26.7%, p = 0.03; ICIs, 21.0% vs. 41.7%, p , 0.01). Overall survival did not differ|

|these two factors remained significant. Metastasis to #10 nodal metastasis was 0% (0/|these two factors remained significant. Metastasis to #10 nodal metastasis was 0% (0/|between the two groups (median, 14.8 months vs. 18.5 months, HR 0.80; 95% CI, 0.59-|between the two groups (median, 14.8 months vs. 18.5 months, HR 0.80; 95% CI, 0.59-|

|28) in patients without both risk factors, 11-12% in those with at least one risk factor, and|28) in patients without both risk factors, 11-12% in those with at least one risk factor, and|1.10, p = 0.17). Moreover, multivariate analysis revealed that EGJA and GA had a|1.10, p = 0.17). Moreover, multivariate analysis revealed that EGJA and GA had a|

||277|Poster Session| |---|---|---|

||Results: 2,930 patients were included in the initial analysis. 206 (7.0%) received ICIs,|Results: 2,930 patients were included in the initial analysis. 206 (7.0%) received ICIs,|

||196 (6.7%) had prior H. pylori infection, and 1,037 (35.4%) had a mucinous subtype.|196 (6.7%) had prior H. pylori infection, and 1,037 (35.4%) had a mucinous subtype.|

||The incidence of ILD was cal-Mucinous cancer subtypes were associated with improved survival (p,0.05) at 3 and 5|The incidence of ILD was cal-Mucinous cancer subtypes were associated with improved survival (p,0.05) at 3 and 5|

||culated from adjudicated drug-related ILD. Results: The interim analysis set included years compared to non-mucinous adenocarcinomas. Mucinous cancers demonstrated|culated from adjudicated drug-related ILD. Results: The interim analysis set included years compared to non-mucinous adenocarcinomas. Mucinous cancers demonstrated|

||1074 patients with median age of 70 years (range: 23-100). Of the 1074 patients, 1051 better survival outcomes than non-mucinous at 10 years, but only among H. pylori-|1074 patients with median age of 70 years (range: 23-100). Of the 1074 patients, 1051 better survival outcomes than non-mucinous at 10 years, but only among H. pylori-|

||(97.9%) received T-DXd as third-line or later treatment. One hundred and eight patients positive patients (p=0.013). H. pylori positivity was associated with worse survival at 3|(97.9%) received T-DXd as third-line or later treatment. One hundred and eight patients positive patients (p=0.013). H. pylori positivity was associated with worse survival at 3|

||(10.1%) had an Eastern Cooperative Oncology Group performance status (ECOG PS) 2 or years (OR: 2.0, p=0.041) among patients taking ICIs but not for patients not receiving|(10.1%) had an Eastern Cooperative Oncology Group performance status (ECOG PS) 2 or years (OR: 2.0, p=0.041) among patients taking ICIs but not for patients not receiving|

||greater, and 32 (3.0%), 3 (0.3%), and 23 (2.1%) patients had severe renal impairment ICIs (OR: 0.8; p=0.325).|greater, and 32 (3.0%), 3 (0.3%), and 23 (2.1%) patients had severe renal impairment ICIs (OR: 0.8; p=0.325).|

||(15# creatinine clearance (CL) ,30 mL/min), end-stage renal disease (CL ,15 mL/|(15# creatinine clearance (CL) ,30 mL/min), end-stage renal disease (CL ,15 mL/|

||min), and ILD/radiation pneumonitis at baseline, respectively (all of which were defined|min), and ILD/radiation pneumonitis at baseline, respectively (all of which were defined|

||as exclusion criteria in clinical trials of T-DXd). Median initial dose of T-DXd was 6.4 mg/|as exclusion criteria in clinical trials of T-DXd). Median initial dose of T-DXd was 6.4 mg/|

||kg (range: 3.1-6.4). Median treatment duration of T-DXd was 4.0 months (range: 0.7-4.0).|kg (range: 3.1-6.4). Median treatment duration of T-DXd was 4.0 months (range: 0.7-4.0).|

||During the first 4 months from the initial treatment, T-DXd was discontinued in 50.9%|During the first 4 months from the initial treatment, T-DXd was discontinued in 50.9%|

||(547/1074) of patients. The most common reasons for treatment discontinuation were|(547/1074) of patients. The most common reasons for treatment discontinuation were|

||disease progression (n=390, 71.3%), adverse events other than ILD (n=76, 13.9%), and|disease progression (n=390, 71.3%), adverse events other than ILD (n=76, 13.9%), and|

|Poster Session OS HR (95% CI)* P value 1.96 (1.48 -2.60) ,0.001 0.81 (0.27 -2.43) 0.71 ILD (n=56, 10.274 275 Treatment group N TTNT HR (95% CI)* P value Chemo-based 573 1.73 (1.37 -2.19) ,0.001 IO-based 100 1.13 (0.47 -2.70) 0.79 Trastuzumab-based 99 0.96 (0.51 -1.83) 0.90 1.21 (0.52 -2.83) 0.66|Poster Session||

|||16,|

||2021 and October 31, 2022 were included. PD-L1 testing patterns and 1L regimens were|2021 and October 31, 2022 were included. PD-L1 testing patterns and 1L regimens were|

||described overall and stratified by PD-L1 testing. The analyses of clinical outcomes are|described overall and stratified by PD-L1 testing. The analyses of clinical outcomes are|

||currently ongoing. Results: A total of 161 patients with mGC/GEJC/EAC met the in-|currently ongoing. Results: A total of 161 patients with mGC/GEJC/EAC met the in-|

||clusion criteria. The median age at index was 67.0 years, 76.4% were male, and the|clusion criteria. The median age at index was 67.0 years, 76.4% were male, and the|

||median follow-up time from index date was 6.7 months. 81 (50.3%) patients had ev-|median follow-up time from index date was 6.7 months. 81 (50.3%) patients had ev-|

|of 318|idence of receiving at least one PD-L1 test (median [interquartile range] time from first|idence of receiving at least one PD-L1 test (median [interquartile range] time from first|

|patients were enrolled, and 312 patients were analyzed, excluding 6 patients due to|test to 1L initiation: 0.4 [-0.1, 1.0] months) among whom 28 (34.6%) had the first test|test to 1L initiation: 0.4 [-0.1, 1.0] months) among whom 28 (34.6%) had the first test|

|double enrollment or miss-enrollment (median age 70 years, performance status 0 or 1/|documented after 1L initiation. Overall, 1L immunotherapy-based regimens were re-|documented after 1L initiation. Overall, 1L immunotherapy-based regimens were re-|

|$2 [87%/12%], 43% patients with ascites). Median OS, rwPFS, and TTF were|ceived by 63 (39.1%) patients, with NIVO+chemo being the most common (n = 47;|ceived by 63 (39.1%) patients, with NIVO+chemo being the most common (n = 47;|

|8.90 months, 4.57 months, and 3.94 months, respectively. Overall ORR was 32.7%; it was|29.2%). 1L fluoropyrimidine-+ platinum-containing chemotherapy and other chemo-|29.2%). 1L fluoropyrimidine-+ platinum-containing chemotherapy and other chemo-|

|43.8% in the 226 patients with a target lesion. Regarding safety, the incidence of|therapies were received by 51 (31.7%) and 42 (26.1%) patients, respectively. Among|therapies were received by 51 (31.7%) and 42 (26.1%) patients, respectively. Among|

|Grade $ 3 AEs was 48.4%. A total of 190/312 (60.9%) patients treated with T-DXd|patients with evidence of PD-L1 testing, 31 (38.3%) received NIVO+chemo, and 37|patients with evidence of PD-L1 testing, 31 (38.3%) received NIVO+chemo, and 37|

|experienced dose reduction, interruption, or discontinuation of T-DXd treatment due to|(45.7%) received chemotherapy alone. Among those without evidence of PD-L1 testing,|(45.7%) received chemotherapy alone. Among those without evidence of PD-L1 testing,|

|AEs. The most common reasons for dose reduction or interruption were neutrophil count|56 (70.0%) received chemotherapy alone, and 16 (20.0%) received NIVO+chemo.|56 (70.0%) received chemotherapy alone, and 16 (20.0%) received NIVO+chemo.|

|decreased, anorexia, and malaise, while the most common reasons for discontinuation|||

|||281|Poster Session| |---|---|---|---|

|disease, Eastern Cooperative Oncology Group (ECOG) performance status 0-2, intol-||||

|erant to CDDP, but tolerant to FOLFOX. FOLFOX (oxaliplatin 85 mg/m², leucovorin||||

|200 mg/m², bolus fluorouracil 400 mg/m², and infusional fluorouracil 2400 mg/m²) was||||

|administered every 14 days. The primary endpoint was the response rate (RR) by RECIST||||

|v1.1 and the null hypothesis of RR was 10%. Based on the assumption of performing a||||

|one-sided test with an a of 0.10, 29 patients were needed to ensure the statistical power||||

|of 90% assuming RR of 30%. Results: In this study, 31 patients were enrolled from 14||||

|hospitals between Apr. 2021, and Jul. 2022 and 30 patients received FOLFOX. The||||

|patient characteristics were: median age, 77 (range 66-89); male/female, 30/1; ECOG||||

|PS 0/1/2, 16/12/3; median creatinine clearance, 49.9 ml/min (33.4-80.2); median G8||||

|score, 12 (range 7-17); and median CARG score, 8 (range 6-13). As the data cutoff of||||

|Jul 2023, all 30 patients discontinued FOLFOX. The reason for treatment discontinuation||||

|was disease progression, 86.7%; adverse events, 13.3%. Median follow-up time (interquartile range: IQR) was 20.2 (IQR 13.7-23.1) months. Median number of cycles administered were 5 (range 1-24). The RR was 22.6% (80%CI 0.13-0.35; p = 0.031) and disease control rate was 42.0%. Median progression-free survival was 3.9 months (95% CI 2.3-6.1). Median overall survival was 13.3 months (95% CI 9.5-not reached). The incidence of grade 3 or higher adverse events was 40% (neutropenia 26.7%, anemia|median progression-free survival (PFS) (20.3 vs 5.1 months; p , 0.001) and a prolonged median overall survival (OS) (33.4 vs 11.7 months; p , 0.001). In the surgery group, 24 (96%) of 25 patients were performed laparoscopic gastrectomy radical laparoscopic gastrectomy with more than D2 lymph node dissection (only one patient underwent open gastrectomy), 19 (76%) patients achieved R0 resection, 2 (8%) patients achieved pathologic complete|median progression-free survival (PFS) (20.3 vs 5.1 months; p , 0.001) and a prolonged median overall survival (OS) (33.4 vs 11.7 months; p , 0.001). In the surgery group, 24 (96%) of 25 patients were performed laparoscopic gastrectomy radical laparoscopic gastrectomy with more than D2 lymph node dissection (only one patient underwent open gastrectomy), 19 (76%) patients achieved R0 resection, 2 (8%) patients achieved pathologic complete||

|3.3%, nausea 6.7%, anorexia 6.7%, infection 6.7%, peripheral sensory neuropathy 3.3%).||||

|282|Poster Session|||

|||compared between||

|||patients receiving PA treatment (n=32) and chemo-PA (n=23) treatment. Exploratory|patients receiving PA treatment (n=32) and chemo-PA (n=23) treatment. Exploratory|

|||biomarker analyses were conducted for the prediction for the efficacy of PA/chemo-PA|biomarker analyses were conducted for the prediction for the efficacy of PA/chemo-PA|

|||treatment. Results: Patients receiving PA regiment had comparable DCR (69% vs 50%,|treatment. Results: Patients receiving PA regiment had comparable DCR (69% vs 50%,|

|||P =0.25) and PFS (median PFS: 6.53 vs 4.73 months, HR=0.70, 95%CI: 0.27-1.78, P|P =0.25) and PFS (median PFS: 6.53 vs 4.73 months, HR=0.70, 95%CI: 0.27-1.78, P|

|Results: Our cohort consisted of 619 cases, of which 456 (73.6%) were denovo metastatic and|=0.52), compared with those treated with combination of chemo-PA regiment as second|=0.52), compared with those treated with combination of chemo-PA regiment as second||

|163(26.4%) were recurrent. The majority (71%) were male, non-Asian (85%) and median age for|or later-line treatment in mGC. Patients with HMCN1 wild-type showed significant|or later-line treatment in mGC. Patients with HMCN1 wild-type showed significant||

|the cohort was 60 years. There were no significant differences in baseline characteristics and|improvements in DCR (77% vs 0%, P =0.023) and PFS (median PFS: 6.53 vs 1.17 months,|improvements in DCR (77% vs 0%, P =0.023) and PFS (median PFS: 6.53 vs 1.17 months,||

|biomarker status (HER2, MSI) between denovo and recurrent groups. Number of metastatic|P =0.0017), versus those with HMCN1 mutations in PA treatment cohort. HMCN1|P =0.0017), versus those with HMCN1 mutations in PA treatment cohort. HMCN1||

|sites was significantly higher in denovo group (Mean:2.3 vs 1.8, p,0.001). A significantly higher percentage of patients received immunotherapy in the first line setting in the recurrent group (8% vs 4%, p:0.04). Using multivariate cox regression and after adjusting for age, performance status and CCI, there was a significant difference in OS favoring recurrent group (aHR:0.70, 95% CI 0.57-0.86, p=,0.001). Using Kaplan Meier curves, median OS was 18.08 months in the recurrent group vs 14.62 months in the denovo metastatic group. There was a significant difference in PFS1 using a multivariate model in favor of the recurrent group (aHR 0.81,95% CI 0.67-0.99, p=0.04), as well as similar improvement in PFS2 for the recurrent|mutations are associated with lower infiltration of endothelial cells and lower score of VEGF ligand-receptor interaction, according to the EPIC and pathway enrichment analysis ( P , 0.05). In addition, analysis of TIME by mIHC revealed that the fraction of CD68+ tumor-associated macrophages in the tumor center was higher in responders than non-responders before treatment (median: 17.59% vs 2.45%, P=0.016). Conclusions: PA regiment and chemo-PA regiment had similar efficacy in second or later line treatment of mGC. HMCN1 mutations maybe a predictive marker for PA|mutations are associated with lower infiltration of endothelial cells and lower score of VEGF ligand-receptor interaction, according to the EPIC and pathway enrichment analysis ( P , 0.05). In addition, analysis of TIME by mIHC revealed that the fraction of CD68+ tumor-associated macrophages in the tumor center was higher in responders than non-responders before treatment (median: 17.59% vs 2.45%, P=0.016). Conclusions: PA regiment and chemo-PA regiment had similar efficacy in second or later line treatment of mGC. HMCN1 mutations maybe a predictive marker for PA||

|Methods: Short-term and long-term postoperative outcomes were analyzed in 203 cases of robot-assisted esophageal cancer resection between 2020/1 and 2023/08. In addition, 33 patients with T3br/T4b who were initially diagnosed with cT3br/T4b and who underwent RAMIE after prior treatment were selected and compared to 48 cT3br/T4b cases with conventional MIE performed at the same time. Results: The mean age of RAMIE patients was 66.2 years, male to female ratio 170:33, preoperative treatment including NAC 150:53, and Clinical Stage I:II:III:IV 41:27:97:38. Surgical outcomes included thoracic surgery time of 200.3 min and total blood loss of 154.4 ml. Perioperative outcomes were Clavien-Dindo Grade 1 or higher: suture failure 4.4%, pneumonia 13.3%, and recurrent nerve palsy 16.7%. Long-term prognostic analysis (MST: 483.6days) showed 3yOS:97.6/94.1/80.3/ 70.9% and 3yDFS:96.2/87.2/66.2/52.4% in cStage I/II/III/IV. Especially in cStage II/III patients, 3yOS: 81.5%, 3yDFS: 71.4%. Long-term outcomes were not significantly dif-ferent from those of conventional thoracoscopic procedures performed at the same time. Perioperative outcomes in cT3br/cT4b patients at initial presentation were pneumonia: 18.1%, recurrent nerve palsy rate: 12.1% (excluding complicated resection cases), and these 3yOS:66.2% and 3yDFS:48.7%. The 3yOS:52.7% and 3yDFS:40.3% of cT3br/285|Methods: Short-term and long-term postoperative outcomes were analyzed in 203 cases of robot-assisted esophageal cancer resection between 2020/1 and 2023/08. In addition, 33 patients with T3br/T4b who were initially diagnosed with cT3br/T4b and who underwent RAMIE after prior treatment were selected and compared to 48 cT3br/T4b cases with conventional MIE performed at the same time. Results: The mean age of RAMIE patients was 66.2 years, male to female ratio 170:33, preoperative treatment including NAC 150:53, and Clinical Stage I:II:III:IV 41:27:97:38. Surgical outcomes included thoracic surgery time of 200.3 min and total blood loss of 154.4 ml. Perioperative outcomes were Clavien-Dindo Grade 1 or higher: suture failure 4.4%, pneumonia 13.3%, and recurrent nerve palsy 16.7%. Long-term prognostic analysis (MST: 483.6days) showed 3yOS:97.6/94.1/80.3/ 70.9% and 3yDFS:96.2/87.2/66.2/52.4% in cStage I/II/III/IV. Especially in cStage II/III patients, 3yOS: 81.5%, 3yDFS: 71.4%. Long-term outcomes were not significantly dif-ferent from those of conventional thoracoscopic procedures performed at the same time. Perioperative outcomes in cT3br/cT4b patients at initial presentation were pneumonia: 18.1%, recurrent nerve palsy rate: 12.1% (excluding complicated resection cases), and these 3yOS:66.2% and 3yDFS:48.7%. The 3yOS:52.7% and 3yDFS:40.3% of cT3br/285|Methods: Short-term and long-term postoperative outcomes were analyzed in 203 cases of robot-assisted esophageal cancer resection between 2020/1 and 2023/08. In addition, 33 patients with T3br/T4b who were initially diagnosed with cT3br/T4b and who underwent RAMIE after prior treatment were selected and compared to 48 cT3br/T4b cases with conventional MIE performed at the same time. Results: The mean age of RAMIE patients was 66.2 years, male to female ratio 170:33, preoperative treatment including NAC 150:53, and Clinical Stage I:II:III:IV 41:27:97:38. Surgical outcomes included thoracic surgery time of 200.3 min and total blood loss of 154.4 ml. Perioperative outcomes were Clavien-Dindo Grade 1 or higher: suture failure 4.4%, pneumonia 13.3%, and recurrent nerve palsy 16.7%. Long-term prognostic analysis (MST: 483.6days) showed 3yOS:97.6/94.1/80.3/ 70.9% and 3yDFS:96.2/87.2/66.2/52.4% in cStage I/II/III/IV. Especially in cStage II/III patients, 3yOS: 81.5%, 3yDFS: 71.4%. Long-term outcomes were not significantly dif-ferent from those of conventional thoracoscopic procedures performed at the same time. Perioperative outcomes in cT3br/cT4b patients at initial presentation were pneumonia: 18.1%, recurrent nerve palsy rate: 12.1% (excluding complicated resection cases), and these 3yOS:66.2% and 3yDFS:48.7%. The 3yOS:52.7% and 3yDFS:40.3% of cT3br/285| |---|---|---|

|286||Poster Session|

|Conclusions: The addition of pembro to tras + chemo did not negatively affect HRQOL during|Conclusions: The addition of pembro to tras + chemo did not negatively affect HRQOL during|Conclusions: The addition of pembro to tras + chemo did not negatively affect HRQOL during|

|treatment. Combined with safety and efficacy data, these results support the use of pembro with|treatment. Combined with safety and efficacy data, these results support the use of pembro with|treatment. Combined with safety and efficacy data, these results support the use of pembro with|

|tras + chemo for first-line treatment of pts with HER2+ advanced gastric cancer. Clinical trial|tras + chemo for first-line treatment of pts with HER2+ advanced gastric cancer. Clinical trial|tras + chemo for first-line treatment of pts with HER2+ advanced gastric cancer. Clinical trial|

|information: NCT03615326. Research Sponsor: Merck Sharp & Dohme LLC, a subsidiary of Merck|information: NCT03615326. Research Sponsor: Merck Sharp & Dohme LLC, a subsidiary of Merck|information: NCT03615326. Research Sponsor: Merck Sharp & Dohme LLC, a subsidiary of Merck|

||Pembro With|Pbo With|

||Tras + Chemo|Tras + Chemo|

||n = 345|n = 340|

|QLQ-C30 GHS/QOL|1.18 (21.12 to 3.49)|2.34 (20.14 to 4.82)|

|QLQ-C30 physical functioning|22.03 (23.91 to 20.15)|22.01 (24.02 to 20.01)|

e loss subscale|26.52 (29.94 to 23.10)|26.62 (210.27 to 22.96)|

||||290|||Poster Session|| |---|---|---|---|---|---|---|---|

|median age 58 years (IQR 25-75); 44% (n=121) reported family history of cancer, 39.6% (n=107) smoking, H. pylori infection was documented in 22% (n=61). Symptoms before diagnosis were present in 98.5% (n=266) of|Methods: We designed and synthesized a series of analogs named (1E,4E,6E)-1,7-|Methods: We designed and synthesized a series of analogs named (1E,4E,6E)-1,7-|Methods: We designed and synthesized a series of analogs named (1E,4E,6E)-1,7-|Methods: We designed and synthesized a series of analogs named (1E,4E,6E)-1,7-|Methods: We designed and synthesized a series of analogs named (1E,4E,6E)-1,7-|||

|nausea 48.9% (n=132), vomiting 48.1% (n=130), dysphagia 21.5% (n=58), and gastrointestinal bleeding 37.8% (n=102). The most common method for histological diagnosis was endoscopy with biopsy in 86.7% (n=234). The median time between the onset of symptoms and histopathological diagnosis was 4.21 (IQR 2.25-8.48) months (m), between the onset of symptoms and the initiation of oncological treatment 5.28 (IQR 2.86-9.52)|based on association theory. Anti-tumor activity was evaluated in vitro using gastric cancer cell lines BGC-823 and SGC-7901. Compound 2 was selected as a prime can-didate based on its potency. Results: Compound 2 demonstrated potent anti-tumor|based on association theory. Anti-tumor activity was evaluated in vitro using gastric cancer cell lines BGC-823 and SGC-7901. Compound 2 was selected as a prime can-didate based on its potency. Results: Compound 2 demonstrated potent anti-tumor|based on association theory. Anti-tumor activity was evaluated in vitro using gastric cancer cell lines BGC-823 and SGC-7901. Compound 2 was selected as a prime can-didate based on its potency. Results: Compound 2 demonstrated potent anti-tumor|based on association theory. Anti-tumor activity was evaluated in vitro using gastric cancer cell lines BGC-823 and SGC-7901. Compound 2 was selected as a prime can-didate based on its potency. Results: Compound 2 demonstrated potent anti-tumor|based on association theory. Anti-tumor activity was evaluated in vitro using gastric cancer cell lines BGC-823 and SGC-7901. Compound 2 was selected as a prime can-didate based on its potency. Results: Compound 2 demonstrated potent anti-tumor|||

|m, and between histopathological diagnosis and oncological treatment 0.60 (IQR 0.13-1.21) m. 72.6% (n=196)|effects in vitro by suppressing growth, migration, and invasion of SGC-7901 and BGC-|effects in vitro by suppressing growth, migration, and invasion of SGC-7901 and BGC-|effects in vitro by suppressing growth, migration, and invasion of SGC-7901 and BGC-|effects in vitro by suppressing growth, migration, and invasion of SGC-7901 and BGC-|effects in vitro by suppressing growth, migration, and invasion of SGC-7901 and BGC-|||

|of cases were stage IV, 14.1% (n=38) stage III, 8.1% (n=22) stage II, 4.8% (n=13) and stage 0 or I. Symptoms (%) Median survival (months) Anorexia Yes (47) 4.7 (2.3-7.04)|p ,0.001|823 cells. Impressively, it prompted cell cycle arrest at the G2/M phase and initiated apoptosis through Bax activation and caspase 3 inhibition. Moreover, in vivo trials on xenograft model nude mice validated the compound's substantial anti-gastric cancer potential while maintaining a favorable safety profile. Conclusions: A group of curcumin analogs exhibiting strong anti-gastric cancer activity was developed. The active compound 2 is capable of inhibiting the growth, colony formation, migration, and in-vasion of gastric cancer cells. It also arrests the cell cycle at the G2/M phase and stimulates the expression of apoptosis-related proteins, showcasing a powerful anti-|823 cells. Impressively, it prompted cell cycle arrest at the G2/M phase and initiated apoptosis through Bax activation and caspase 3 inhibition. Moreover, in vivo trials on xenograft model nude mice validated the compound's substantial anti-gastric cancer potential while maintaining a favorable safety profile. Conclusions: A group of curcumin analogs exhibiting strong anti-gastric cancer activity was developed. The active compound 2 is capable of inhibiting the growth, colony formation, migration, and in-vasion of gastric cancer cells. It also arrests the cell cycle at the G2/M phase and stimulates the expression of apoptosis-related proteins, showcasing a powerful anti-|823 cells. Impressively, it prompted cell cycle arrest at the G2/M phase and initiated apoptosis through Bax activation and caspase 3 inhibition. Moreover, in vivo trials on xenograft model nude mice validated the compound's substantial anti-gastric cancer potential while maintaining a favorable safety profile. Conclusions: A group of curcumin analogs exhibiting strong anti-gastric cancer activity was developed. The active compound 2 is capable of inhibiting the growth, colony formation, migration, and in-vasion of gastric cancer cells. It also arrests the cell cycle at the G2/M phase and stimulates the expression of apoptosis-related proteins, showcasing a powerful anti-|823 cells. Impressively, it prompted cell cycle arrest at the G2/M phase and initiated apoptosis through Bax activation and caspase 3 inhibition. Moreover, in vivo trials on xenograft model nude mice validated the compound's substantial anti-gastric cancer potential while maintaining a favorable safety profile. Conclusions: A group of curcumin analogs exhibiting strong anti-gastric cancer activity was developed. The active compound 2 is capable of inhibiting the growth, colony formation, migration, and in-vasion of gastric cancer cells. It also arrests the cell cycle at the G2/M phase and stimulates the expression of apoptosis-related proteins, showcasing a powerful anti-|823 cells. Impressively, it prompted cell cycle arrest at the G2/M phase and initiated apoptosis through Bax activation and caspase 3 inhibition. Moreover, in vivo trials on xenograft model nude mice validated the compound's substantial anti-gastric cancer potential while maintaining a favorable safety profile. Conclusions: A group of curcumin analogs exhibiting strong anti-gastric cancer activity was developed. The active compound 2 is capable of inhibiting the growth, colony formation, migration, and in-vasion of gastric cancer cells. It also arrests the cell cycle at the G2/M phase and stimulates the expression of apoptosis-related proteins, showcasing a powerful anti-||

|No (62)|6.1 (3.8-8.4)||Clinical T4||3.04 (1.89-4.21)|0.038||

|Median follow-up (interquartile range) was 6.0 (2.429.8) mo for NIVO+chemo and 6.1 (2.529.7) mo for|Median follow-up (interquartile range) was 6.0 (2.429.8) mo for NIVO+chemo and 6.1 (2.529.7) mo for|Median follow-up (interquartile range) was 6.0 (2.429.8) mo for NIVO+chemo and 6.1 (2.529.7) mo for|Median follow-up (interquartile range) was 6.0 (2.429.8) mo for NIVO+chemo and 6.1 (2.529.7) mo for| |---|---|---|---|

|10.2217.9] mo vs 10.0 [8.9211.5] mo, P = 0.047). Univariate Cox regression analysis of OS yielded a|10.2217.9] mo vs 10.0 [8.9211.5] mo, P = 0.047). Univariate Cox regression analysis of OS yielded a|10.2217.9] mo vs 10.0 [8.9211.5] mo, P = 0.047). Univariate Cox regression analysis of OS yielded a|10.2217.9] mo vs 10.0 [8.9211.5] mo, P = 0.047). Univariate Cox regression analysis of OS yielded a|

|QLQ-C30 nausea/vomiting subscale|23.24 (25.60 to 20.89)|23.57 (26.08 to 21.05)|

|QLQ-C30 appetite loss subscale|26.52 (29.94 to 23.10)|26.62 (210.27 to 22.96)|

||||Tislelizumab (TIS) plus chemotherapy (Chemo) vs placebo (PBO) plus|Tislelizumab (TIS) plus chemotherapy (Chemo) vs placebo (PBO) plus|Tislelizumab (TIS) plus chemotherapy (Chemo) vs placebo (PBO) plus|Tislelizumab (TIS) plus chemotherapy (Chemo) vs placebo (PBO) plus|Tislelizumab (TIS) plus chemotherapy (Chemo) vs placebo (PBO) plus|

||||chemo as first-line (1L) treatment of advanced gastric or gastroesophageal|||||

|tologically diagnosed esophageal squamous or adenosquamous carcinoma who started systemic CTx for metastatic or recurrent disease between January 1, 2013 and December 31, 2018 at 16 institutions in Japan. With a cutoff date of December 31, 2020, the treatment patterns and outcomes, including response rate (RR), progression-free survival (PFS), and overall survival (OS) for first through third CTx, were analyzed. Results: A total of 891 pts were included in this analysis. The median age (range) was 67 (23-90) years, 84.9% of pts were male, histological types were squamous cell carcinoma in 99.0% and adenosquamous carcinoma in 1.0%, and disease status was metastatic in 35.8% of pts. Most common first-, second-, and third-line regimens were fluoropyrimidine-based (72.4%), taxane-based (64.6%), and taxane-based (48.2%), respectively. Of the pts who received the first-line CTx, the second-and third-line CTx were administered in 51.2% and 21.4% of pts, re-spectively. The RR from first-to third-line CTx was 24.2%, 6.5%, and 2.2%, and mPFS was 4.1 months (mo) (95% CI 3.7-4.5), 3.1 mo (95% CI 2.8-3.6), and 3.0 mo (95% CI 2.5-4.2), respectively. The mOS from the first-, second-, and third-line CTx were 12.6 mo (95%CI 11.4-13.6), 8.3 mo (95% CI 7.7-9.6), and 8.0 mo (95% CI 7.1-9.5), respectively. As for OS from first-line CTx, a trend of improvement was shown before (median 11.9 mo, 95% CI 10.6-13.3) or after (median 13.2 mo, 95% CI 11.3-14.5) the median time of treatment initiation (March 2016). Pts with recurrent disease (mOS 26.6 mo, 95% CI 24.7-28.6) had a better prognosis|junction adenocarcinoma (Results: TIS + chemo had improved outcomes than PBO + chemo (Table) as indicated by least-squares mean change from baseline to Cycle 6 for QLQ-C30 GHS/QoL (2.52 [95% CI:0.29 to 4.74]), physical functioning (2.46 [95% CI: 0.49 to 4.43] ), fatigue (-3.01 [95% CI: -5.78 to -0.24]), and the STO22 index score (-1.62 [95% CI: -3.12 to -0.12] ), as well as maintaining upper gastrointestinal (GI) symptoms (-1.74 [95% CI: -3.55 to 0.06)] and pain (-1.88 [95% CI: -4.03 to 0.27] ). Pts receiving TIS + chemo had a lower risk for deterioration of GHS/QoL (0.77 [95% CI: 0.60 to 0.98]), physical functioning (0.72 [0.57 to 0.92] ), STO22 index score (0.64 [0.45 to 0.92]), pain/discomfort (HR: 0.74 [0.58-0.96] ), and upper GI symptoms (0.73 [0.56 to 0.95]). Conclusions: Cycle 4 Cycle 4 Cycle 6 Cycle 6|junction adenocarcinoma (Results: TIS + chemo had improved outcomes than PBO + chemo (Table) as indicated by least-squares mean change from baseline to Cycle 6 for QLQ-C30 GHS/QoL (2.52 [95% CI:0.29 to 4.74]), physical functioning (2.46 [95% CI: 0.49 to 4.43] ), fatigue (-3.01 [95% CI: -5.78 to -0.24]), and the STO22 index score (-1.62 [95% CI: -3.12 to -0.12] ), as well as maintaining upper gastrointestinal (GI) symptoms (-1.74 [95% CI: -3.55 to 0.06)] and pain (-1.88 [95% CI: -4.03 to 0.27] ). Pts receiving TIS + chemo had a lower risk for deterioration of GHS/QoL (0.77 [95% CI: 0.60 to 0.98]), physical functioning (0.72 [0.57 to 0.92] ), STO22 index score (0.64 [0.45 to 0.92]), pain/discomfort (HR: 0.74 [0.58-0.96] ), and upper GI symptoms (0.73 [0.56 to 0.95]). Conclusions: Cycle 4 Cycle 4 Cycle 6 Cycle 6||||||

|than those with stage 4 disease at initial diagnosis (mOS 14.9 mo, 95% CI 13.2-16.3). Of the 293 pts who relapsed after esophagectomy with perioperative CTx or radical chemo-||TIS + chemo n=501 Mean (95% CI)|PBO + chemo n=496 Mean (95% CI)|TIS + chemo n=501 Mean (95% CI)|PBO + chemo n=496 Mean (95% CI)|||

||||QLQ-C30|1.35 (-0.24, 2.94) -0.45 (-2.04, 1.13) 0.93 (-0.71, 2.57) -1.58 (-3.24, 0.07)|1.35 (-0.24, 2.94) -0.45 (-2.04, 1.13) 0.93 (-0.71, 2.57) -1.58 (-3.24, 0.07)|1.35 (-0.24, 2.94) -0.45 (-2.04, 1.13) 0.93 (-0.71, 2.57) -1.58 (-3.24, 0.07)|1.35 (-0.24, 2.94) -0.45 (-2.04, 1.13) 0.93 (-0.71, 2.57) -1.58 (-3.24, 0.07)|

||||GHS/QoL|||||

||||Physical|-2.47 (-3.77, -1.18) -3.92 (-5.21, -2.62) -2.76 (-4.22, -1.30) -5.22 (-6.69, -3.75)|-2.47 (-3.77, -1.18) -3.92 (-5.21, -2.62) -2.76 (-4.22, -1.30) -5.22 (-6.69, -3.75)|-2.47 (-3.77, -1.18) -3.92 (-5.21, -2.62) -2.76 (-4.22, -1.30) -5.22 (-6.69, -3.75)|-2.47 (-3.77, -1.18) -3.92 (-5.21, -2.62) -2.76 (-4.22, -1.30) -5.22 (-6.69, -3.75)|

||||functioning|||||

||||Fatigue|1.75 (-0.09, 3.60)|3.07 (1.23, 4.91)|1.71 (-0.32, 3.75|4.73 (2.68, 6.77)|

||||QLQ-STO22|||||

||||Index score|||||

||||Dietary restrictions -0.31 (-1.75, 1.12) 0.61 (-0.82, 2.05) -0.25 (-1.79, 1.30) 1.08 (-0.48, 2.63)|Dietary restrictions -0.31 (-1.75, 1.12) 0.61 (-0.82, 2.05) -0.25 (-1.79, 1.30) 1.08 (-0.48, 2.63)|Dietary restrictions -0.31 (-1.75, 1.12) 0.61 (-0.82, 2.05) -0.25 (-1.79, 1.30) 1.08 (-0.48, 2.63)|Dietary restrictions -0.31 (-1.75, 1.12) 0.61 (-0.82, 2.05) -0.25 (-1.79, 1.30) 1.08 (-0.48, 2.63)|Dietary restrictions -0.31 (-1.75, 1.12) 0.61 (-0.82, 2.05) -0.25 (-1.79, 1.30) 1.08 (-0.48, 2.63)|

||||GI symptoms|-3.14 (-4.40, -1.87) -1.54 (-2.80, -0.28) -3.24 (-4.58, -1.90) -1.49 (-2.84, -0.14)|-3.14 (-4.40, -1.87) -1.54 (-2.80, -0.28) -3.24 (-4.58, -1.90) -1.49 (-2.84, -0.14)|-3.14 (-4.40, -1.87) -1.54 (-2.80, -0.28) -3.24 (-4.58, -1.90) -1.49 (-2.84, -0.14)|-3.14 (-4.40, -1.87) -1.54 (-2.80, -0.28) -3.24 (-4.58, -1.90) -1.49 (-2.84, -0.14)|

|291|Poster Session|292|||Poster Session|||

||3% (n=144) women,|||||||

|pts, most common were: weight loss 77.4% (n=209), fatigue 51.9% (n=140), early satiety 51.1% (n=138),|diphenyl hepta-1,4,6-trien-3-one analogues inspired by the o-methoxy phenyl group|diphenyl hepta-1,4,6-trien-3-one analogues inspired by the o-methoxy phenyl group|diphenyl hepta-1,4,6-trien-3-one analogues inspired by the o-methoxy phenyl group|diphenyl hepta-1,4,6-trien-3-one analogues inspired by the o-methoxy phenyl group|diphenyl hepta-1,4,6-trien-3-one analogues inspired by the o-methoxy phenyl group|||

|No (53) Early satiety Yes (52) No (48)|8.4 (6.5-10.3) 7.5 (5.6-9.4) 6.03 (2.9-9.07)|,0.001|gastric cancer effect in vitro. Furthermore, it demonstrates significant anti-gastric cancer activity in vivo while maintaining a favorable safety profile. Our research un-|||||

|Abdominal pain||||||||

|Yes (72)|5.4 (3.3-7.4)|0.02||||||

|No (28)|9.8 (7.8-11.7)|||||||

|Ascites||||||||

|Yes (20) No (80) Palpable mass Yes (15) No (85) Yes (38) Gastrointestinal bleeding|0.9 (0.2-1.6) 4.2 (3.4-5.05) 1.5 (0-5.4) 7.5 (5.5-9.5) 8.1 (4.2-11.9)|0.03 0.01 ,0.001|Variable TRG Histology Diffuse||Hazard Ratio (95% CI) 1.42 (1.05-2.24) 2.08 (1.34-3.50)|Hazard Ratio (95% CI) 1.42 (1.05-2.24) 2.08 (1.34-3.50)|P 0.008 0.001|

|chemo. There were 87 (37.7%) deaths in the NIVO+chemo cohort and 138 (46.5%) in the chemo cohort.|chemo. There were 87 (37.7%) deaths in the NIVO+chemo cohort and 138 (46.5%) in the chemo cohort.|chemo. There were 87 (37.7%) deaths in the NIVO+chemo cohort and 138 (46.5%) in the chemo cohort.|chemo. There were 87 (37.7%) deaths in the NIVO+chemo cohort and 138 (46.5%) in the chemo cohort.|

|NIVO+chemo demonstrated superior overall survival (OS) in the overall cohort, with a 12-mo OS rate of|NIVO+chemo demonstrated superior overall survival (OS) in the overall cohort, with a 12-mo OS rate of|NIVO+chemo demonstrated superior overall survival (OS) in the overall cohort, with a 12-mo OS rate of|NIVO+chemo demonstrated superior overall survival (OS) in the overall cohort, with a 12-mo OS rate of|

|53.3% vs 38.1% for chemo and a 2.6-mo improvement in median OS (12.6 [95% confidence interval (CI),|53.3% vs 38.1% for chemo and a 2.6-mo improvement in median OS (12.6 [95% confidence interval (CI),|53.3% vs 38.1% for chemo and a 2.6-mo improvement in median OS (12.6 [95% confidence interval (CI),|53.3% vs 38.1% for chemo and a 2.6-mo improvement in median OS (12.6 [95% confidence interval (CI),|

|hazard ratio (HR) of 0.76 (95% CI, 0.5821.00; P = 0.048) and multivariate Cox regression yielded an HR of|hazard ratio (HR) of 0.76 (95% CI, 0.5821.00; P = 0.048) and multivariate Cox regression yielded an HR of|hazard ratio (HR) of 0.76 (95% CI, 0.5821.00; P = 0.048) and multivariate Cox regression yielded an HR of|hazard ratio (HR) of 0.76 (95% CI, 0.5821.00; P = 0.048) and multivariate Cox regression yielded an HR of|

|0.74 (95% CI, 0.5620.98; P = 0.033) for NIVO+chemo vs chemo. There was also a consistent trend toward|0.74 (95% CI, 0.5620.98; P = 0.033) for NIVO+chemo vs chemo. There was also a consistent trend toward|0.74 (95% CI, 0.5620.98; P = 0.033) for NIVO+chemo vs chemo. There was also a consistent trend toward|0.74 (95% CI, 0.5620.98; P = 0.033) for NIVO+chemo vs chemo. There was also a consistent trend toward|

|OS benefit with NIVO+chemo vs chemo in all CPS subgroups (Table). Multivariate analysis in the CPS $ 1|OS benefit with NIVO+chemo vs chemo in all CPS subgroups (Table). Multivariate analysis in the CPS $ 1|OS benefit with NIVO+chemo vs chemo in all CPS subgroups (Table). Multivariate analysis in the CPS $ 1|OS benefit with NIVO+chemo vs chemo in all CPS subgroups (Table). Multivariate analysis in the CPS $ 1|

|subgroup yielded a HR of 0.51 (95% CI, 0.3020.89) for NIVO+chemo vs chemo but was not feasible in|subgroup yielded a HR of 0.51 (95% CI, 0.3020.89) for NIVO+chemo vs chemo but was not feasible in|subgroup yielded a HR of 0.51 (95% CI, 0.3020.89) for NIVO+chemo vs chemo but was not feasible in|subgroup yielded a HR of 0.51 (95% CI, 0.3020.89) for NIVO+chemo vs chemo but was not feasible in|

|other subgroups due to sample size. Conclusions: NIVO+chemo showed superior OS vs chemo alone in|other subgroups due to sample size. Conclusions: NIVO+chemo showed superior OS vs chemo alone in|other subgroups due to sample size. Conclusions: NIVO+chemo showed superior OS vs chemo alone in|other subgroups due to sample size. Conclusions: NIVO+chemo showed superior OS vs chemo alone in|

|(13.4%/13.323 Poster Session|

|Pairwise treatment comparisons for PFS and OS with 1L therapies vs FOLFOX/CAPOX.*||||||| |---|---|---|---|---|---|---|

|||Median PFS: median (95% CI), mo HR b (95% CI) HR c (95% CI)|4.1 (2.7, 7.6)|6.8 (5.6, 8.3) 0.75 (0.44, 1.26) 0.66 (0.44, 0.99) 6.9 (6.0, 9.9) 0.52 (0.30, 0.91)|||

|||Median OS: median (95% CI), mo HR b (95% CI) HR c (95% CI)|9.9 (7.6, 23.2)|13.1 (12.2, 16.3) 0.75 (0.40, 1.39) 0.80 (0.49, 1.30) 16.0 (11.3, 21.7) 0.64 (0.35, 1.20)|||

|327|Poster Session| |---|---|

||330|Poster Session| |---|---|---|

|331|Poster Session||

||phase I||

|dose finding study using a standard 3+3 design, subjects received four escalating dose levels (dl) of irinotecan/paclitaxel (mg/m 2 ): 135/45 (dl #1), 150/45 (dl #2), 135/67.5 (dl|||

|#3), and 135/90 (dl #4) in combination with tislelizumab 200 mg plus oxaliplatin 85 mg/|||

|m 2 , levoleucovorin 200 mg/m 2 , and 5-FU 2400 mg/m 2 for 46 hours every 2 weeks.|||

|Primary endpoints were safety, tolerability, and recommended phase 2 dose (RP2D).|||

|Results: Fifteen subjects with treatment naïve AGC were enrolled (3 each in dl #1, dl #2,|||

|and dl #3 and 6 in dl #4). The median age was 65 years (range 36-72); 80% were male.|||

|Two subjects (13.3%) were diagnosed with gastroesophageal junction cancer, 9 (60%)|||

|had poorly differentiated disease, and 5 (33.3%) had liver metastasis. PD-L1 CPS scores|||

|were: 5 (n=5); 1 (n=1); and 0 (n=9). All subjects were evaluated for dose-limiting toxicity|||

|(DLT). One DLT (grade 4 neutropenia) occurred within 28 days in dl #4. No maximum|||

|tolerated dose was reached; the RP2D was dl #4. All subjects had $1 treatment-related|||

|adverse event (TRAE) and 10 (66.7%) had $1 grade 3-4 TRAE per NCI CTC-AE 5.0. The|||

|most frequent grade 3-4 TRAEs were neutropenia (n=8; 53.3%), anemia (n=2; 13.3%), and|||

|increased glutamyl transpeptidase (n=2 pts; 13.3%). Confirmed objective response rate|||

||||334 338||||||Poster Session Poster Session|Poster Session Poster Session|Poster Session Poster Session| |---|---|---|---|---|---|---|---|---|---|---|---|

||||||||||Surgical re-|||

||||section included total gastrectomy in 108 (53.2%), adjacent organ resection in 24|section included total gastrectomy in 108 (53.2%), adjacent organ resection in 24|section included total gastrectomy in 108 (53.2%), adjacent organ resection in 24|section included total gastrectomy in 108 (53.2%), adjacent organ resection in 24|section included total gastrectomy in 108 (53.2%), adjacent organ resection in 24|section included total gastrectomy in 108 (53.2%), adjacent organ resection in 24|section included total gastrectomy in 108 (53.2%), adjacent organ resection in 24|section included total gastrectomy in 108 (53.2%), adjacent organ resection in 24|section included total gastrectomy in 108 (53.2%), adjacent organ resection in 24|

||||(11.8%), and extended (D1+/D2) lymphadenectomy in 193 (95.1%) patients. Pathologic|(11.8%), and extended (D1+/D2) lymphadenectomy in 193 (95.1%) patients. Pathologic|(11.8%), and extended (D1+/D2) lymphadenectomy in 193 (95.1%) patients. Pathologic|(11.8%), and extended (D1+/D2) lymphadenectomy in 193 (95.1%) patients. Pathologic|(11.8%), and extended (D1+/D2) lymphadenectomy in 193 (95.1%) patients. Pathologic|(11.8%), and extended (D1+/D2) lymphadenectomy in 193 (95.1%) patients. Pathologic|(11.8%), and extended (D1+/D2) lymphadenectomy in 193 (95.1%) patients. Pathologic|(11.8%), and extended (D1+/D2) lymphadenectomy in 193 (95.1%) patients. Pathologic|(11.8%), and extended (D1+/D2) lymphadenectomy in 193 (95.1%) patients. Pathologic|

||||complete response was achieved (pCR) in 32 (15.8%) patients. The median OS was 8.4|complete response was achieved (pCR) in 32 (15.8%) patients. The median OS was 8.4|complete response was achieved (pCR) in 32 (15.8%) patients. The median OS was 8.4|complete response was achieved (pCR) in 32 (15.8%) patients. The median OS was 8.4|complete response was achieved (pCR) in 32 (15.8%) patients. The median OS was 8.4|complete response was achieved (pCR) in 32 (15.8%) patients. The median OS was 8.4|complete response was achieved (pCR) in 32 (15.8%) patients. The median OS was 8.4|complete response was achieved (pCR) in 32 (15.8%) patients. The median OS was 8.4|complete response was achieved (pCR) in 32 (15.8%) patients. The median OS was 8.4|

||||(95% confidence interval [CI] 6.5-not reached) years, and the 5-year OS rate was 65.2%|(95% confidence interval [CI] 6.5-not reached) years, and the 5-year OS rate was 65.2%|(95% confidence interval [CI] 6.5-not reached) years, and the 5-year OS rate was 65.2%|(95% confidence interval [CI] 6.5-not reached) years, and the 5-year OS rate was 65.2%|(95% confidence interval [CI] 6.5-not reached) years, and the 5-year OS rate was 65.2%|(95% confidence interval [CI] 6.5-not reached) years, and the 5-year OS rate was 65.2%|(95% confidence interval [CI] 6.5-not reached) years, and the 5-year OS rate was 65.2%|(95% confidence interval [CI] 6.5-not reached) years, and the 5-year OS rate was 65.2%|(95% confidence interval [CI] 6.5-not reached) years, and the 5-year OS rate was 65.2%|

||||(95% CI 57.8-73.5%). Patients with pCR had a 5-year OS rate of 89.1% (95% CI 78.1-|(95% CI 57.8-73.5%). Patients with pCR had a 5-year OS rate of 89.1% (95% CI 78.1-|(95% CI 57.8-73.5%). Patients with pCR had a 5-year OS rate of 89.1% (95% CI 78.1-|(95% CI 57.8-73.5%). Patients with pCR had a 5-year OS rate of 89.1% (95% CI 78.1-|(95% CI 57.8-73.5%). Patients with pCR had a 5-year OS rate of 89.1% (95% CI 78.1-|(95% CI 57.8-73.5%). Patients with pCR had a 5-year OS rate of 89.1% (95% CI 78.1-|(95% CI 57.8-73.5%). Patients with pCR had a 5-year OS rate of 89.1% (95% CI 78.1-|(95% CI 57.8-73.5%). Patients with pCR had a 5-year OS rate of 89.1% (95% CI 78.1-|(95% CI 57.8-73.5%). Patients with pCR had a 5-year OS rate of 89.1% (95% CI 78.1-|

||||100.0%). On multivariable analysis, D1+/D2 lymphadenectomy (HR 0.21 [95% CI 0.088-|100.0%). On multivariable analysis, D1+/D2 lymphadenectomy (HR 0.21 [95% CI 0.088-|100.0%). On multivariable analysis, D1+/D2 lymphadenectomy (HR 0.21 [95% CI 0.088-|100.0%). On multivariable analysis, D1+/D2 lymphadenectomy (HR 0.21 [95% CI 0.088-|100.0%). On multivariable analysis, D1+/D2 lymphadenectomy (HR 0.21 [95% CI 0.088-|100.0%). On multivariable analysis, D1+/D2 lymphadenectomy (HR 0.21 [95% CI 0.088-|100.0%). On multivariable analysis, D1+/D2 lymphadenectomy (HR 0.21 [95% CI 0.088-|100.0%). On multivariable analysis, D1+/D2 lymphadenectomy (HR 0.21 [95% CI 0.088-|100.0%). On multivariable analysis, D1+/D2 lymphadenectomy (HR 0.21 [95% CI 0.088-|

||||0.51]), post-treatment pathologic (yp) T (ypT3 vs ypT0, HR 3.11 [95% CI 1.09-8.82] ; ypT4|0.51]), post-treatment pathologic (yp) T (ypT3 vs ypT0, HR 3.11 [95% CI 1.09-8.82] ; ypT4|0.51]), post-treatment pathologic (yp) T (ypT3 vs ypT0, HR 3.11 [95% CI 1.09-8.82] ; ypT4|0.51]), post-treatment pathologic (yp) T (ypT3 vs ypT0, HR 3.11 [95% CI 1.09-8.82] ; ypT4|0.51]), post-treatment pathologic (yp) T (ypT3 vs ypT0, HR 3.11 [95% CI 1.09-8.82] ; ypT4|0.51]), post-treatment pathologic (yp) T (ypT3 vs ypT0, HR 3.11 [95% CI 1.09-8.82] ; ypT4|0.51]), post-treatment pathologic (yp) T (ypT3 vs ypT0, HR 3.11 [95% CI 1.09-8.82] ; ypT4|0.51]), post-treatment pathologic (yp) T (ypT3 vs ypT0, HR 3.11 [95% CI 1.09-8.82] ; ypT4|0.51]), post-treatment pathologic (yp) T (ypT3 vs ypT0, HR 3.11 [95% CI 1.09-8.82] ; ypT4|

|Characteristics Male Median age, years (range)|9 51.5|37.5% 22-66|vs ypT0, HR 5.51 [95% CI 1.64-18.5]) and N stages (ypN1 vs ypN0, HR 2.41 [95% CI 1.13-5.13] ; ypN2 vs ypN0, HR 2.43 [95% CI 1.14-5.20]; ypN3 vs ypN0, HR 4.70 [95% CI 2.09-10.6] ), incidental distant metastasis at time of resection (HR 3.75 [95% CI 1.50-9.37]),|vs ypT0, HR 5.51 [95% CI 1.64-18.5]) and N stages (ypN1 vs ypN0, HR 2.41 [95% CI 1.13-5.13] ; ypN2 vs ypN0, HR 2.43 [95% CI 1.14-5.20]; ypN3 vs ypN0, HR 4.70 [95% CI 2.09-10.6] ), incidental distant metastasis at time of resection (HR 3.75 [95% CI 1.50-9.37]),|vs ypT0, HR 5.51 [95% CI 1.64-18.5]) and N stages (ypN1 vs ypN0, HR 2.41 [95% CI 1.13-5.13] ; ypN2 vs ypN0, HR 2.43 [95% CI 1.14-5.20]; ypN3 vs ypN0, HR 4.70 [95% CI 2.09-10.6] ), incidental distant metastasis at time of resection (HR 3.75 [95% CI 1.50-9.37]),|vs ypT0, HR 5.51 [95% CI 1.64-18.5]) and N stages (ypN1 vs ypN0, HR 2.41 [95% CI 1.13-5.13] ; ypN2 vs ypN0, HR 2.43 [95% CI 1.14-5.20]; ypN3 vs ypN0, HR 4.70 [95% CI 2.09-10.6] ), incidental distant metastasis at time of resection (HR 3.75 [95% CI 1.50-9.37]),|vs ypT0, HR 5.51 [95% CI 1.64-18.5]) and N stages (ypN1 vs ypN0, HR 2.41 [95% CI 1.13-5.13] ; ypN2 vs ypN0, HR 2.43 [95% CI 1.14-5.20]; ypN3 vs ypN0, HR 4.70 [95% CI 2.09-10.6] ), incidental distant metastasis at time of resection (HR 3.75 [95% CI 1.50-9.37]),|vs ypT0, HR 5.51 [95% CI 1.64-18.5]) and N stages (ypN1 vs ypN0, HR 2.41 [95% CI 1.13-5.13] ; ypN2 vs ypN0, HR 2.43 [95% CI 1.14-5.20]; ypN3 vs ypN0, HR 4.70 [95% CI 2.09-10.6] ), incidental distant metastasis at time of resection (HR 3.75 [95% CI 1.50-9.37]),|vs ypT0, HR 5.51 [95% CI 1.64-18.5]) and N stages (ypN1 vs ypN0, HR 2.41 [95% CI 1.13-5.13] ; ypN2 vs ypN0, HR 2.43 [95% CI 1.14-5.20]; ypN3 vs ypN0, HR 4.70 [95% CI 2.09-10.6] ), incidental distant metastasis at time of resection (HR 3.75 [95% CI 1.50-9.37]),|vs ypT0, HR 5.51 [95% CI 1.64-18.5]) and N stages (ypN1 vs ypN0, HR 2.41 [95% CI 1.13-5.13] ; ypN2 vs ypN0, HR 2.43 [95% CI 1.14-5.20]; ypN3 vs ypN0, HR 4.70 [95% CI 2.09-10.6] ), incidental distant metastasis at time of resection (HR 3.75 [95% CI 1.50-9.37]),|vs ypT0, HR 5.51 [95% CI 1.64-18.5]) and N stages (ypN1 vs ypN0, HR 2.41 [95% CI 1.13-5.13] ; ypN2 vs ypN0, HR 2.43 [95% CI 1.14-5.20]; ypN3 vs ypN0, HR 4.70 [95% CI 2.09-10.6] ), incidental distant metastasis at time of resection (HR 3.75 [95% CI 1.50-9.37]),|

|ECOG PS 3 PLT < 25*10 9 /L|16 9|66.7% 37.5%|and postoperative complications (HR 2.06 [95% CI 1.21-3.52]) were associated with OS.|and postoperative complications (HR 2.06 [95% CI 1.21-3.52]) were associated with OS.|and postoperative complications (HR 2.06 [95% CI 1.21-3.52]) were associated with OS.|and postoperative complications (HR 2.06 [95% CI 1.21-3.52]) were associated with OS.|and postoperative complications (HR 2.06 [95% CI 1.21-3.52]) were associated with OS.|and postoperative complications (HR 2.06 [95% CI 1.21-3.52]) were associated with OS.|and postoperative complications (HR 2.06 [95% CI 1.21-3.52]) were associated with OS.|and postoperative complications (HR 2.06 [95% CI 1.21-3.52]) were associated with OS.|and postoperative complications (HR 2.06 [95% CI 1.21-3.52]) were associated with OS.|

|Median DIC score (range)|6|5 -8||||||||||

|Previous gastrectomy|10|41.7%||||||||||

|Adjuvant chemotherapy|9|37.5%||||||||||

|End points||||||||||||

|HeR rate, % (95% CI)|83.3%|67.3%-99.4%||||||||||

|Median TTHeR (range)|13|7-36||||||||||

|OMM|3|12.5%||||||||||

|Median OS, days (95% CI)|242|132-352||||||||||

|Grade 3 AEs|7|29.2%||||||||||

|335 phase employed a 3+3 dose escalation design, pts were treated with fruquintinib 3mg/d, po, Poster Session The Ib d1-14 (dose level; DL1), 4mg/d (DL2), or 5mg/d (DL3) in combination with fixed dose of toripalimab (240mg, iv, d1), oxaliplatin (130 mg/m 2 , iv, d1) and S-1 (40-60mg based on BSA, po, d1-14) every 3 weeks. Fruquintinib 5mg/d was defined as the RP2D. Of the 16 pts evaluable for tumor response, 9 pts achieved PR, 7 pts achieved SD. The ORR was 56.3% (9/16), the DCR was 100% (16/16). Pts with PD-L1 CPS ＜1 were more likely to achieve better responses (4PR in 6 pts, ORR-66.7%). After a median follow-up of 5.4 months, the median PFS was 9.3 (95% CI: 4.76-NA) months and OS result was not mature. Median DOR was not reached and two responders were estimated to have a response duration $8.0 months. Majority of TRAEs were grade 1-2, including neutrophil count decreased (64.336 Local Lesion size Submucosal injection Total Lifting not done Lifting done Lesion size Submucosal|Smaller than 10 mm (n=544) n Local recurrence 544 14 (2.6) 251 7 (2.8) 293 7 (2.4) Larger than 10 mm (n=74)|Smaller than 10 mm (n=544) n Local recurrence 544 14 (2.6) 251 7 (2.8) 293 7 (2.4) Larger than 10 mm (n=74)|Smaller than 10 mm (n=544) n Local recurrence 544 14 (2.6) 251 7 (2.8) 293 7 (2.4) Larger than 10 mm (n=74)|Smaller than 10 mm (n=544) n Local recurrence 544 14 (2.6) 251 7 (2.8) 293 7 (2.4) Larger than 10 mm (n=74)|Smaller than 10 mm (n=544) n Local recurrence 544 14 (2.6) 251 7 (2.8) 293 7 (2.4) Larger than 10 mm (n=74)|Smaller than 10 mm (n=544) n Local recurrence 544 14 (2.6) 251 7 (2.8) 293 7 (2.4) Larger than 10 mm (n=74)|n 58 9 49|< 5 mm (n=58) Local recurrence 1 (1.7) 0 (0.0) 1 (2.0) 11-15 mm (n=43)|Poster Session 5 -10 mm (n=486) Local recurrence 13 (2.7) 7 (2.9) 6 (2.5) 16-20 mm n 486 242 244 > 20 mm (n=) (n=2)|Poster Session 5 -10 mm (n=486) Local recurrence 13 (2.7) 7 (2.9) 6 (2.5) 16-20 mm n 486 242 244 > 20 mm (n=) (n=2)|Poster Session 5 -10 mm (n=486) Local recurrence 13 (2.7) 7 (2.9) 6 (2.5) 16-20 mm n 486 242 244 > 20 mm (n=) (n=2)|

||||injection|n|Local recurrence|n|Local recurrence|n|Local recurrence|n|Local recurrence|

||||Total|74|7 (9.5)|43|3 (7.0)|29|4 (13.8)|2|0 (0.0)|

||||Lifting not done|42|1 (2.4)|20|0 (0.0)|22|1 (4.5)|0|0|

||||Lifting done|32|6 (18.8)|23|3 (13.0)|7|3 (42.9)|2|0 (0.0)|

|340|Poster Session| |---|---|

|. Research Sponsor: Eli Lily; National||

|Cancer Center Research and Development Fund; 26-A-22, 29-A-15.|The best|

|overall response indicated that there were 14 PR (73.7%), 2 SD (10.5%) and 3 NE (15.8%).|overall response indicated that there were 14 PR (73.7%), 2 SD (10.5%) and 3 NE (15.8%).|

|Therefore, the preliminary ORR was 73.7% (95%CI: 48.8%-90.9%), DCR was 84.2% (95%|Therefore, the preliminary ORR was 73.7% (95%CI: 48.8%-90.9%), DCR was 84.2% (95%|

|CI: 60.4%-96.6%). Median PFS of the 19 patients was not yet reached. Additionally,|CI: 60.4%-96.6%). Median PFS of the 19 patients was not yet reached. Additionally,|

|safety profile exhibited that the regimen was tolerable. The most common treatment-|safety profile exhibited that the regimen was tolerable. The most common treatment-|

|emergent adverse events among the 23 patients with the incidence .20% were leu-|emergent adverse events among the 23 patients with the incidence .20% were leu-|

|||||||346|Poster Session| |---|---|---|---|---|---|---|---|

||KEYNOTE-590|KEYNOTE-859|KEYNOTE-590|KEYNOTE-590 GEJC +|KEYNOTE-859|||

||GEJC n=91|GEJC n=334|GEJC + EAC n=201|EAC + CPS ‡1 n=169|GEJC + CPS ‡1 n=287|||

|OS, median, mo|12.7 vs 10.0|14.2 vs 12.0|11.6 vs 9.9|13.0 vs 10.1|14.2 vs 12.1|||

|OS HR (95% CI)|0.73 (0.45-1.17)|0.74 (0.58-0.94)|0.75 (0.55-1.03)|0.73 (0.51-1.03)|0.71 (0.55-0.93)|||

|PFS, median, mo|6.3 vs 6.1|6.8 vs 5.7|8.0 vs 5.7|8.0 vs 5.7|6.8 vs 5.6|||

|PFS HR (95% CI)|0.65 (0.39-1.08)|0.78 (0.61-1.01)|0.56 (0.40-0.78)|0.55 (0.38-0.79)|0.76 (0.58-1.00|||

|343||||Poster Session|344|Poster Session||

|Advantages of robotic surgery for advanced gastric cancer in short-term|Prophylactic para-aortic lymph node dissection after neoadjuvant chemo-|Prophylactic para-aortic lymph node dissection after neoadjuvant chemo-||||||

|outcomes: A single-center retrospective study using propensity score|therapy for gastric cancer with bulky lymph node metastasis. First Author:|therapy for gastric cancer with bulky lymph node metastasis. First Author:||||||

|matching. First Author: Masaru Komatsu, National Cancer Center Hospital East,|Furukawa Kenichiro, Division of Gastric Surgery, Shizuoka Cancer Center, Nagaizumi,|Furukawa Kenichiro, Division of Gastric Surgery, Shizuoka Cancer Center, Nagaizumi,||||||

|Kashiwa, Japan|||||Japan|||

|Background: Importantly, in the RG group, there were fewer complications with Clavien-Dindo (CD)|Background: 57%), and other regimens in D2+PAND group included docetaxel+S-1+cisplatin or oxaliplatin. The D2+PAND group had longer operation time (p=0.006), and tended toward more undifferentiated histological type (p=0.063), better pathological response|||||||

|classification $Grade II (11.5 vs 21.5%, P = 0.04) and CD classification $Grade III (0.8%|(p=0.086), and higher rate of adjuvant chemotherapy (p=0.090) than the D2 group. The|(p=0.086), and higher rate of adjuvant chemotherapy (p=0.090) than the D2 group. The||||||

|vs 6.9%, P = 0.01). Postoperative hospital stay was shorter (8 vs 9 days, P = 0.01) in the|ypStage was similar between the two groups. Pathological PAN metastasis was de-|ypStage was similar between the two groups. Pathological PAN metastasis was de-||||||

|RG group. Conclusions: RG for advanced gastric cancer has the potential to reduce|tected in two patients (18%) in D2+PAND group. Recurrence occurred in seven (70%)|tected in two patients (18%) in D2+PAND group. Recurrence occurred in seven (70%)||||||

|||Total|333|45|388|

|306 Nivolumab (NIVO) + chemotherapy (chemo) vs chemo as first-line (1L) Poster Session treatment for advanced gastric cancer/gastroesophageal junction cancer/ esophageal adenocarcinoma (GC/GEJC/EAC): 4 year (yr) follow-up of (EPOC2003). 310 Phase 2 study of trastuzumab deruxtecan as neoadjuvant treatment for HER2-positive gastric and gastroesophageal junction adenocarcinoma Poster Session||||||| |---|---|---|---|---|---|---|

|30,4%. The median PFS was 6.2 months (95% CI 4.4-7.6). The ORR was 21.7% with 1 between the two groups, more early complications were observed in the primary surgery|0.05 and the power of 90%. Results: Thirty patients from 14 institutions were enrolled|0.05 and the power of 90%. Results: Thirty patients from 14 institutions were enrolled|0.05 and the power of 90%. Results: Thirty patients from 14 institutions were enrolled|0.05 and the power of 90%. Results: Thirty patients from 14 institutions were enrolled|0.05 and the power of 90%. Results: Thirty patients from 14 institutions were enrolled|0.05 and the power of 90%. Results: Thirty patients from 14 institutions were enrolled|

|complete response. With a median follow-up of 11.8 months at data cutoff, the median group than in secondary surgery group (50% vs. 20.6%, P = .021).|from September 2017 to June 2022. The number of patients with compete response,|from September 2017 to June 2022. The number of patients with compete response,|from September 2017 to June 2022. The number of patients with compete response,|from September 2017 to June 2022. The number of patients with compete response,|from September 2017 to June 2022. The number of patients with compete response,|from September 2017 to June 2022. The number of patients with compete response,|

|OS was not reached. Grade $3 treatment-related adverse events were reported in 9 Conclusions: Secondary surgery did not increase the risk of LNM. The long-term|partial response, stable disease, progressive disease, and inevaluable were, 0, 20, 8, 1,|partial response, stable disease, progressive disease, and inevaluable were, 0, 20, 8, 1,|partial response, stable disease, progressive disease, and inevaluable were, 0, 20, 8, 1,|partial response, stable disease, progressive disease, and inevaluable were, 0, 20, 8, 1,|partial response, stable disease, progressive disease, and inevaluable were, 0, 20, 8, 1,|partial response, stable disease, progressive disease, and inevaluable were, 0, 20, 8, 1,|

|(39.1%) patients. Conclusions: An interim analysis demonstrates modest efficacy and outcomes were comparable. Therefore, attempts to perform upfront ESD for superfi-|and 1, respectively. The response rate was 66.7%, with the 90% confidence interval of|and 1, respectively. The response rate was 66.7%, with the 90% confidence interval of|and 1, respectively. The response rate was 66.7%, with the 90% confidence interval of|and 1, respectively. The response rate was 66.7%, with the 90% confidence interval of|and 1, respectively. The response rate was 66.7%, with the 90% confidence interval of|and 1, respectively. The response rate was 66.7%, with the 90% confidence interval of|

|an acceptable safety profile of nivolumab in combination with chemotherapy in patients cial esophageal squamous cell cancers are justified. Research Sponsor: None.|50.1 -80.7% (p = 0.049). The curative resection rate was 93.3%. The protocol treatment|50.1 -80.7% (p = 0.049). The curative resection rate was 93.3%. The protocol treatment|50.1 -80.7% (p = 0.049). The curative resection rate was 93.3%. The protocol treatment|50.1 -80.7% (p = 0.049). The curative resection rate was 93.3%. The protocol treatment|50.1 -80.7% (p = 0.049). The curative resection rate was 93.3%. The protocol treatment|50.1 -80.7% (p = 0.049). The curative resection rate was 93.3%. The protocol treatment|

|with FGFR2-positive, PD-L1-positive metastatic GC. Further follow-up is ongoing. 1. Wainberg, Lancet Oncol. 2022. 2. Tsimafeyeu, Invest New Drugs. 2023. Clinical trial information: NCT05859477. Research Sponsor: Bureau for Cancer Research; June 5,|completion rate was 53.3%. The preoperative chemotherapy completion rate was 93.3%. Demographics, baseline characteristics and efficacy outcomes (N=10). The operation completion rate was 90.0%. The postoperative chemotherapy completion rate was 70.0%. The relative dose intensities were 94.8% for capecitabine and 95.2% for Median age, years (range) 68 (58-82)|completion rate was 53.3%. The preoperative chemotherapy completion rate was 93.3%. Demographics, baseline characteristics and efficacy outcomes (N=10). The operation completion rate was 90.0%. The postoperative chemotherapy completion rate was 70.0%. The relative dose intensities were 94.8% for capecitabine and 95.2% for Median age, years (range) 68 (58-82)|completion rate was 53.3%. The preoperative chemotherapy completion rate was 93.3%. Demographics, baseline characteristics and efficacy outcomes (N=10). The operation completion rate was 90.0%. The postoperative chemotherapy completion rate was 70.0%. The relative dose intensities were 94.8% for capecitabine and 95.2% for Median age, years (range) 68 (58-82)|completion rate was 53.3%. The preoperative chemotherapy completion rate was 93.3%. Demographics, baseline characteristics and efficacy outcomes (N=10). The operation completion rate was 90.0%. The postoperative chemotherapy completion rate was 70.0%. The relative dose intensities were 94.8% for capecitabine and 95.2% for Median age, years (range) 68 (58-82)|completion rate was 53.3%. The preoperative chemotherapy completion rate was 93.3%. Demographics, baseline characteristics and efficacy outcomes (N=10). The operation completion rate was 90.0%. The postoperative chemotherapy completion rate was 70.0%. The relative dose intensities were 94.8% for capecitabine and 95.2% for Median age, years (range) 68 (58-82)|completion rate was 53.3%. The preoperative chemotherapy completion rate was 93.3%. Demographics, baseline characteristics and efficacy outcomes (N=10). The operation completion rate was 90.0%. The postoperative chemotherapy completion rate was 70.0%. The relative dose intensities were 94.8% for capecitabine and 95.2% for Median age, years (range) 68 (58-82)|

|2022.||ECOG PS, %||0||3 (30)|

|||||1||7 (70)|

|||Prior systemic regimens, %||2||4 (40)|

|||||$3||6 (60)|

|||DC rate, % (OR or SD16+) (1-sided 90% CI)|||10 (1, 100)|10 (1, 100)|

|||OR rate, % (95% CI)||||10 (,1, 45)|

|||Median PFS, wks (95% CI)||||8 (2, 13)|

|||Median OS, wks (95% CI)||||17 (9, 35)|

|||314|Poster Session| |---|---|---|---|

||Results: A total of 1,011 patients un-|Results: We enrolled 1,349 patients (YA group: 105|Results: We enrolled 1,349 patients (YA group: 105|

|derwent ESD for EGC, achieved CR and were followed up more than 12 months. Among|patients [7.8%], OA group: 1244 [92.2%] ). Compared with OA group, YA group contained|patients [7.8%], OA group: 1244 [92.2%] ). Compared with OA group, YA group contained||

|them, 86 patients had metachronous cancers (85/1011, 8.4%) during 53.4 months of|more female patients (36.2 vs. 26.5%, P= 0.033), their tumor was located at middle third|more female patients (36.2 vs. 26.5%, P= 0.033), their tumor was located at middle third||

|follow-up. Compared with patients without metachronous cancers, those with meta-|(41.0 vs. 29.6%, P= 0.006) and was depressed (40.0 vs. 28.8%, P= 0.001), and had more|(41.0 vs. 29.6%, P= 0.006) and was depressed (40.0 vs. 28.8%, P= 0.001), and had more||

|chronous cancers were significantly older (66.9 vs. 63.8 years, P=0.004) and had higher|undifferentiated (30.5 vs. 12.1%, P, 0.001) and diffuse type (22.9 vs. 7.3%, P, 0.001)|undifferentiated (30.5 vs. 12.1%, P, 0.001) and diffuse type (22.9 vs. 7.3%, P, 0.001)||

|NLR (2.1 vs. 1.8, P=0.002), however, other inflammatory indexes such as PLR and ESR|histology. However, synchronous tumor was less frequent in YA group (2.9 vs. 12.4%, P=|histology. However, synchronous tumor was less frequent in YA group (2.9 vs. 12.4%, P=||

|were not significantly different between two groups. Kaplan-Meier analysis showed that|0.001). When we sorted 884 patients who achieved curative resection and were|0.001). When we sorted 884 patients who achieved curative resection and were||

|patients with NLR $ 2.0 had significantly higher possibility of metachronous cancer|followed-up longer than 12 months, Kaplan-Meier analysis showed that metachronous|followed-up longer than 12 months, Kaplan-Meier analysis showed that metachronous||

|compared with patients with NLR , 2.0 (P=0.049 by log rank test). After adjusting age,|neoplasm (dysplasia or cancer) and metachronous cancer were significantly less in YA|neoplasm (dysplasia or cancer) and metachronous cancer were significantly less in YA||

|atrophy and Helicobacter pylori status, NLR was the only significant risk factor for|group than OA group (P= 0.003 and 0.013, respectively), however, local recurrence was|group than OA group (P= 0.003 and 0.013, respectively), however, local recurrence was||

|metachronous cancer (odds ratio: 1.33, 95% confidence interval: 1.007-1.665, P=0.011).|not significantly different between two groups. Conclusions: ESD is a favorable and|not significantly different between two groups. Conclusions: ESD is a favorable and||

|Conclusions: NLR may have a predictive value for occurrence of metachronous cancer|effective therapeutic modality for EGC patients who are aged under 50, once curative|effective therapeutic modality for EGC patients who are aged under 50, once curative||

|after CR of EGC by ESD. Further thorough investigation is necessary to validate this|resection is achieved. Research Sponsor: None.|||

|outcome. Research Sponsor: None.||||

|315|Poster Session|316|Poster Session|

|daily on days 1 through 21 of a 21-day cycle, with Pembro 200 mg i.v. on day 1. The primary endpoint was PFS-6, with H0=5%, Ha$20%, requiring n=27 evaluable pts and n$4 pts with PFS-6 to reject H0 in favor of Ha. Results: 27 pts were enrolled. Median age 58 years (24-87), female (n=14), ECOG 0/1= 13/14, GC/GEJ= 16/11, Non-Hispanic White/Hispanic/Asian= 12/8/7. The primary endpoint was met with n=6 pts having PFS.6mo. After a median follow-up of 31.4mo (range 3.3-42.5), PFS-6 is 22.2% (95% CI 9.0-39.0). The median PFS and OS are 2.3mo (95% CI 1.7-4.1) and 5.5mo (3.1-14.0), respectively. The most common mutations were TP53 (78.3%) and CDH1/PIK3CA/CTNNB1 (17.4% each). In exploratory analyses, 5/7 (71.4%) pts in the top quartile for PFS had alterations in the cMET-PI3K-AKT pathway. The most common any grade (G) treatment related adverse events (TRAE) were diarrhea (25.9%), fatigue (18.5%), hypertension and muscle cramps (14.8% each). G3-4 TRAE were seen in n=3 pts (Hypertension, Thromboembolic event, esophageal perforation; each n=1). No G5 were observed. Conclusions: The addition of Cabo to Pembro shows clinical benefit in ICI resistant or refractory mGEA with an observed PFS-6 of 22.2%. The regimen appears tolerable with no new safety signals. An exploratory|in patients eligible for surgery with HER2+ locally advanced GC or adenocarcinoma of the GEJ. Methods: Patients aged 18-75 years were randomized 1:1 to atezolizumab + tras-tuzumab + XELOX (Arm A) or trastuzumab + XELOX (Arm B) and received the regimen for three neoadjuvant cycles (3 weeks per cycle) and five adjuvant cycles. Treatment ad-ministration was atezolizumab 1200 mg, trastuzumab 6 mg/kg, oxaliplatin 130 mg/m 2 intravenously on Day 1, and capecitabine 1000 mg/m 2 orally twice daily on Days 1-14 of each 3-week cycle. The primary endpoint was the pathological complete regression (pCR) rate. Secondary endpoints were the objective response rate (ORR) during neoadjuvant systemic therapy (NAST) and the R0 resection rate. Time-to-event endpoints are not re-ported because of immaturity. Efficacy endpoints were analyzed in the intention-to-treat population. The clinical cutoff date for the primary analysis was 12 March 2023. Results: Forty-two Asian patients who provided informed consent were screened and randomized to Arm A (n = 21) or Arm B (n = 21); all patients completed NAST. Most patients were male (92.9%), and the median (range) age was 61 (33-72) years in Arm A and 65 (49-72) years in Arm B. The pCR rate was 38.1% (8/21) in Arm A and 14.3% (3/21) in Arm B (treatment difference: 23.8% [90% confidence interval (CI), 1.3%-44.7%]). The pCR rate was|||

|||Steady State (600 mg/m 2 Q3W)| |---|---|---|

|C max (mg/mL) AUC 21d (day$mg/mL) C trough (mg/mL) C ave (mg/mL)|434 (96) 2164 (589) 43.9 (25.1) -|425 (91) 3359 (1254) 101 (51) 140 (50)|

|TRAEs were grade 1 or 2, 1 pt (11.1%) had a grade 3 TRAE (decreased neutrophils [10mg/kg]). In expansion, 26 pts with CLDN18.2 moderate-to-high expression ($2+ membrane staining intensity in $40% of tumor cells) were included in the safety set. 24(92.3%) pts had TRAEs, the most common being nausea (65.4%), vomiting (53.8%), hypoproteinemia (53.8%), anemia (50.0%), fatigue (26.9%) and decreased neutrophils (23.1%). 3 pts (11.318 First-line (1L) nivolumab (NIVO) plus chemotherapy (chemo) vs chemo in Poster Session patients (pts) with advanced gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma (GC/GEJC/EAC): Methods: Adults with previously untreated, unresectable advanced or metastatic, non-HER2+ GC/GEJC/EAC were enrolled regardless of programmed death ligand 1 (PD-L1) expression. Randomized pts received NIVO (360 mg Q3W or 240 mg Q2W) + chemo (XELOX Q3W or FOLFOX Q2W), NIVO + ipilimumab, or chemo. Dual primary endpoints for NIVO + chemo vs chemo were OS and progression-free survival (PFS) by blinded independent central review (BICR) in pts with PD-L1 combined positive score (CPS) $ 5. Results: 208 Chinese pts were randomized to NIVO + chemo or chemo. At 49-month (mo) minimum follow-up, NIVO + chemo continued to demonstrate OS and PFS benefit vs chemo in pts with PD-L1 CPS $ 5 and in all randomized pts (Table). The 4-yr OS rate was 25% with NIVO + chemo vs 11% with chemo in pts with PD-L1 CPS $ 5 and 21% vs 9% in all randomized pts. Objective response rate (ORR; 95% CI) per BICR in pts with PD-L1 CPS $ 5 who had measurable lesions at baseline was 68% (56-79) with NIVO + chemo vs 48% (36-60) with chemo; corresponding ORR in all randomized pts was 66% (55-76) and 45% (35-56). Responses were more durable with NIVO + chemo vs chemo both in pts with PD-L1 CPS $ 5 (median duration of response [mDOR; 95% CI] 12.5 mo [7.2-23.4] vs 6.9 mo [3.9-8.5] ) and in all randomized pts (mDOR [95% CI] 12.5 mo [7.2-17.7] vs 5.6 mo [4.4-8.3]). Efficacy PD-L1 CPS ‡ 5 All Randomized NIVO + chemo (n = 75) Chemo (n = 81) NIVO + chemo (n = 99) Chemo (n = 109) mOS (95% CI), mo 15.5 (11.9-21.1) 9.6 (8.0-12.1) 14.3 (11.5-16.5) 10.3 (8.1-12.1) HR (95% CI) 0.56 (0.39-0.80) 0. 62 (0.45-0.84) mPFS a (95% CI), mo 8.5 (6.0-14.0) 4.3 (4.1-6.5) 8.3 (6.2-12.4) 5.6 (4.2-6.8) HR (95% CI) 0.51 (0.34-0.76) 0.57 (0.41-0.80) Safety, all treated pts: TRAEs, n (%) NIVO + chemo (n = 99) Chemo (n = 106) Any grade/grade 3-4 98 (99)/65 (66) 100 (94)/53 (50) Leading to discontinuation 50 (51)/20 (20) 28 (26)/11 (10) 319 Poster Session Overall survival was similar among all patients (HR 0.72 [0.67,0.77], p,0.001, I2=0.0%), patients with no liver metastasis (HR 0.73 [0.67,0.81] , p,0.001, I2=0.0%), and patients with liver metastasis (HR 0.74 [0.67,0.81], p,0.001, I2=0.0%), indicating that ICIs' benefit on OS is consistent. Progression-free survival (PFS) was also similar among all patients (HR 0.63 [0.57,0.70] , p,0.001, I2=54.7%); those with no liver metastasis (HR 0.62 [0.51,0.76], p,0.001, I2=62.3%), and with liver metastasis (HR 0.66 [0.57,0.76] , p,0.001, I2-0.0%). Funnel plots were used to identify a potential bias for studies included in the analysis and 320 Poster Session 30mg/m2 IV every week for 2 cycles)-based CRT (180-200cGy per fraction for 10-13 fractions) followed by pembrolizumab (200mg IV every 3 weeks for 18 cycles) in patients with locally advanced ESCC who had high-risk recurrence features in esophagectomy tumor tissues, including involved or close margin (#1 mm), extranodal extension (ENE) of involved lymph node, and ypN2-3, following neoadjuvant CRT (ClinicalTrials.gov Identifier: NCT03322267). Primary end-point was 1-year relapse-free survival (RFS) rate in comparison with a historical control of 32%. 1 Secondary endpoints included RFS, overall survival (OS), and toxicity. Results: Between Nov 2018 and Dec 2022, we enrolled a total of 25 patients with high risk recurrence features, including margin #1 mm (18 patients), ENE of involved lymph node (9), and ypN2-3 (9). Majority of patients were male (88%) and current smokers (84%). The median follow-up duration was 16.5 months (95% CI 10.6-27.1). One-year RFS rate was 63.3% (95% CI 44.5-79.8). Median RFS and OS were 15.3 months (95% CI 10.2-20.4) and 38.3 months (95% CI 10.2-66.3), respectively. Any grade treatment emergent adverse events (TEAEs) occurred in 56% and 75% of patients during cisplatin-based CRT and pembrolizumab treatment, respectively. Grade 3 TEAEs were infrequent, including leukopenia (4%), pancreatitis (4%), infection (8%), and colitis (4%). There was control group, early LELC patients were younger, had a higher prevalence of proximally located tumors, more frequent Epstein-Barr virus (EBV) infection, more frequent deep submucosal invasion (SM2 or SM3, 85.4% versus 29.9%, P , 0.001) but less frequent lymphatic invasion (4.9% versus 16.2%, P = 0.009). Among tumors with deep sub-mucosal invasion, early LELC patients had smaller tumor sizes, less frequent lymphatic invasion (5.7% versus 40.1%, P , 0.001) and a lower rate of LNM (7.1% versus 19.4%, P = 0.016) than the control group. LNM rates of LELC patients with mucosal, shallow submucosal invasion (SM1) and deep submucosal invasion were 0%, 0%, and 7.1%, no grade 4 TRAE. Results: Compared to the respectively.| |---|

|To detect a 3-month difference| |---|

|in median OS [hazard ratio (HR) = 0.73] with study-wise, one-sided alpha level of 5% and|

|power of 75%, 240 patients were required. Results: A total of 240 patients were|

|randomly assigned to bDCF (n = 121) and CF (n = 119) between September 2014 to April|

|2021. Patient background in bDCF/CF arm was median age, 65/64 years; ECOG per-|

|formance status 0, 69%/75%; metastatic disease, 63%/67%, $2 metastatic organs, 59%/|

|56%; squamous cell carcinoma, 94%/97%. As a data cut-off of April 2023, all 240|

|patients discontinued protocol treatment. The reasons for treatment discontinuation in|

|bDCF/CF arm were disease progression, 58%/71%; adverse events (AEs), 35%/27%;|

|refusal, 1%/1%; others, 7%/5%, respectively. With a median follow-up of 15.3 months|

|(m), bDCF arm was not superior to CF arm in terms of OS with a median of 16.2 m versus|

|14.8 m [HR, 0.90; 95% confidence interval (CI), 0.68-1.19; p = 0.23], however,|

|progression-free survival (PFS) in bDCF arm was favorable compared to CF arm with a|

|median of 6.0 m versus 5.2 m (HR, 0.68; 95% CI, 0.52-0.88). Response rate in bDCF/CF|

|arm was 52.8%/45.6%. Major grade 3 or 4 AEs observed in bDCF/CF arm were neu-|

|tropenia (37.8%/27.1%); anorexia (25.2%/16.1%); fatigue (10.1%/15.3%); hyponatremia|

||Median HR for PFS (95% CrI)|Median HR for OS (95% CrI)|||||

|Zolbetuximab + FOLFOX/CAPOX|0.71 (0.61, 0.82)|0.78 (0.67, 0.89)|||||

|Nivolumab + FOLFOX/CAPOX|0.79 (0.70, 0.89)|0.79 (0.70, 0.88)|||||

|Pembrolizumab + CF/CAPOX|0.76 (0.68, 0.86)|0.78 (0.69, 0.88)|||||

|Pembrolizumab + CX|0.80 (0.53, 1.20)|0.98 (0.65, 1.48)|||||

|CF|1.18 (0.90, 1.54)|1.35 (1.06, 1.72)|||||

|CX|0.94 (0.66, 1.36)|1.15 (0.79, 1.67)|||||

|SC|1.13 (0.84, 1.52)|1.27 (0.96, 1.66)|||||

|||324|324|324|||

|||Key efficacy endpoints.|||||

||||CT a (control)|Atezo + CT a|Tira + atezo + CT a||

||||n=23|n=65|n=62||

|||Confirmed ORR Responders, n (%)|11 (47.8%)|35 (53.8%)|42 (67.7%)||

|||(95% CI) Diff in ORR b , % Diff in ORR c , %|(26.8, 69.4)|(41.0, 66.3) 6.0%|13.9%|(54.7, 79.1) 19.9%|

|||NIVO+chemo|Chemo Alone|

||Median (95% CI), mo|15.4 (9.0218.2)|8.9 (7.1211.2)|

||Univariate HR (95% CI)|0.67 (0.4021.11)||

|CPS < 5|N|4 7|7 4|

||Median (95% CI), mo|17.0 (10.72NR)|10.0 (7.1215.5)|

||Univariate HR (95% CI)|0.57 (0.2921.12)||

|74s|ESOPHAGEAL AND GASTRIC CANCER||||| |---|---|---|---|---|---|

|||298||Poster Session|Poster Session|

|||Feasibility of functional evaluation in older adults with gastroesophageal|Feasibility of functional evaluation in older adults with gastroesophageal|Feasibility of functional evaluation in older adults with gastroesophageal|Feasibility of functional evaluation in older adults with gastroesophageal|

|||cancer using fitness trackers. First Author: Lauren Laderman, Temple University|cancer using fitness trackers. First Author: Lauren Laderman, Temple University|cancer using fitness trackers. First Author: Lauren Laderman, Temple University|cancer using fitness trackers. First Author: Lauren Laderman, Temple University|

|||Hospital, Philadelphia, PA||||

|Among low-risk patients, 213 (88.0%) were treated with surgery (CRT+S) and had a|of age .75 and SMG risk group showed 33.3% mortality among patients .75 in Q1 for SMG,|of age .75 and SMG risk group showed 33.3% mortality among patients .75 in Q1 for SMG,|of age .75 and SMG risk group showed 33.3% mortality among patients .75 in Q1 for SMG,|of age .75 and SMG risk group showed 33.3% mortality among patients .75 in Q1 for SMG,|of age .75 and SMG risk group showed 33.3% mortality among patients .75 in Q1 for SMG,|

|||Kashiwa, Japan|||||

|||Results: From 22 institutions, 149 patients were enrolled. As defined, all patients|Results: From 22 institutions, 149 patients were enrolled. As defined, all patients|Results: From 22 institutions, 149 patients were enrolled. As defined, all patients|Results: From 22 institutions, 149 patients were enrolled. As defined, all patients|Results: From 22 institutions, 149 patients were enrolled. As defined, all patients|

|previously untreated pts with advanced GC/GEJC/EAC in the RW setting. A trend toward OS benefit was|previously untreated pts with advanced GC/GEJC/EAC in the RW setting. A trend toward OS benefit was|previously untreated pts with advanced GC/GEJC/EAC in the RW setting. A trend toward OS benefit was|previously untreated pts with advanced GC/GEJC/EAC in the RW setting. A trend toward OS benefit was|

|also observed in all CPS subgroups, which will be further examined in future analyses with larger samples|also observed in all CPS subgroups, which will be further examined in future analyses with larger samples|also observed in all CPS subgroups, which will be further examined in future analyses with larger samples|also observed in all CPS subgroups, which will be further examined in future analyses with larger samples|

|and longer follow-up. Clinical trial information: NCT02872116. Research Sponsor: Bristol Myers Squibb.|and longer follow-up. Clinical trial information: NCT02872116. Research Sponsor: Bristol Myers Squibb.|and longer follow-up. Clinical trial information: NCT02872116. Research Sponsor: Bristol Myers Squibb.|and longer follow-up. Clinical trial information: NCT02872116. Research Sponsor: Bristol Myers Squibb.|

|Kaplan-Meier estimates of OS in CPS subgroups.||||

|Subgroups||(n = 231)|(n = 297)|

|CPS ‡ 1|N|9 5|6 3|

|CPS ‡ 5|N|6 8|2 9|

||Median (95% CI), mo|14.6 (8.62NR)|8.9 (5.6211.2)|

||Univariate HR (95% CI)|0.58 (0.3121.10)||

|Results: 82 pts were enrolled, majority male (74%), median age 73 (65-91), stage III/IV (82%) disease on first line therapy (79%). Cancer sites included gastric (32%), esophageal PA Detected N (%) GA Detected N (%) Captured by Both N (%) Kappa Functional Status 9 (11) 35 (43) 8 (10) 0.229 Nutrition 5 (6) 42 (51) 3 (4) 0.021 Comorbidities 49 (60) 20 (24) 15 (18) 0.1352 Psychological Distress 10 (12) 27 (33) 4 (5) 0.0465 Cognition 0 (0) 7 (9) 0 (0) 0 Social Support 4 (5) 28 (34) 2 (2) 0.0433 Chemotherapy Toxicity Risk 5 (6) 33 (40) 4 (5) 0.117 Poster Session similar in both groups (21% vs 17%, p=0.285). 299 Background: median SPD was 2264. Patients with # median SPD were older (75 vs 72 p=0.034), female (32% vs 14% p=0.093), Black (24% vs 9% p=0.068), and living alone (29% vs 14% ucation level (#12 yrs 35% vs 31% p=0.802) and Stage (.2 82% vs 80% p=0.99). Patients with SPD below the median were more likely to have $ 2 abnormalities on GA (68% vs. 40%, p=0.03), self-reported PS .2 (24% vs 0% p=0.013), and impaired IADL (33% vs 9% p=0.064). Patients with lower SPD had higher rates $Gr 3 toxicity (47% vs 20% p=0.022) and hospitalization (32% vs 6% p=0.006). The rate of abnormal TUG was 300 Poster Session Results: 112 patients had 127 SEMS inserted at The Christie. Patients' International Dysphagia Diet Standardisation Initiative (IDDSI) score significantly improved after SEMS insertion (N=120); prior to SEMS 62% were only managing liquids and purees (IDDSI 3 and 4) and 24% were not able to eat enterally. Post SEMS, 76% tolerated textured foods (IDDSI 5 and above) and only 21.5% were limited to liquids/purees. We observed a significant reduction in the rate of weight loss (% body weight/10 days) following SEMS insertion (-0.010 6 0.009 vs. -0.001 6 0.010, P , 0.001). 12% of (43%), GEJ (26%). Domains N=82 p=0.153). Patients SPD below and above the median had similar distributions of ed-patients experienced grade 3||||||

|||Results: Mean age was 62.8 years (SD 10.4). Patients were 84.4% male with 87.4% White,|Results: Mean age was 62.8 years (SD 10.4). Patients were 84.4% male with 87.4% White,|Results: Mean age was 62.8 years (SD 10.4). Patients were 84.4% male with 87.4% White,|Results: Mean age was 62.8 years (SD 10.4). Patients were 84.4% male with 87.4% White,|

|||10.6% Black, 1.8% Hispanic, and 0.3% Asian. Histologically, 86.4% of patients had adeno-|10.6% Black, 1.8% Hispanic, and 0.3% Asian. Histologically, 86.4% of patients had adeno-|10.6% Black, 1.8% Hispanic, and 0.3% Asian. Histologically, 86.4% of patients had adeno-|10.6% Black, 1.8% Hispanic, and 0.3% Asian. Histologically, 86.4% of patients had adeno-|

|||carcinoma while 11.4% had squamous cell carcinoma. Anastomotic leak occurred in 8.1%,|carcinoma while 11.4% had squamous cell carcinoma. Anastomotic leak occurred in 8.1%,|carcinoma while 11.4% had squamous cell carcinoma. Anastomotic leak occurred in 8.1%,|carcinoma while 11.4% had squamous cell carcinoma. Anastomotic leak occurred in 8.1%,|

|||pneumonia in 16.7%, ventilation greater than 48 hours in 20.7%, and discharge to home in|pneumonia in 16.7%, ventilation greater than 48 hours in 20.7%, and discharge to home in|pneumonia in 16.7%, ventilation greater than 48 hours in 20.7%, and discharge to home in|pneumonia in 16.7%, ventilation greater than 48 hours in 20.7%, and discharge to home in|

|||82.1% of patients. 30-day readmission occurred in 16.4% and 90-day mortality in 6.1% of|82.1% of patients. 30-day readmission occurred in 16.4% and 90-day mortality in 6.1% of|82.1% of patients. 30-day readmission occurred in 16.4% and 90-day mortality in 6.1% of|82.1% of patients. 30-day readmission occurred in 16.4% and 90-day mortality in 6.1% of|

|||patients. 8 patients did not have CT scans available. Analysis of 90-day mortality as a function|patients. 8 patients did not have CT scans available. Analysis of 90-day mortality as a function|patients. 8 patients did not have CT scans available. Analysis of 90-day mortality as a function|patients. 8 patients did not have CT scans available. Analysis of 90-day mortality as a function|

|significantly longer overall survival compared to CRT (p,0.0001), with median survival|9.6% for patients ,75 in Q1 for SMG, 5.6% for patients .75 in Q234 for SMG, and 2.2% in 264|9.6% for patients ,75 in Q1 for SMG, 5.6% for patients .75 in Q234 for SMG, and 2.2% in 264|9.6% for patients ,75 in Q1 for SMG, 5.6% for patients .75 in Q234 for SMG, and 2.2% in 264|9.6% for patients ,75 in Q1 for SMG, 5.6% for patients .75 in Q234 for SMG, and 2.2% in 264|9.6% for patients ,75 in Q1 for SMG, 5.6% for patients .75 in Q234 for SMG, and 2.2% in 264|

|of 40.6mo (95% CI 32.3, 55.5) in the CRT+S group and 17.3mo (95% CI 13.3, 36.4) in the|patients ,75 in Q234 for SMG for subjects who had available scan data (n = 388).|patients ,75 in Q234 for SMG for subjects who had available scan data (n = 388).|patients ,75 in Q234 for SMG for subjects who had available scan data (n = 388).|patients ,75 in Q234 for SMG for subjects who had available scan data (n = 388).|patients ,75 in Q234 for SMG for subjects who had available scan data (n = 388).|

|CRT group. Among 74 high risk patients, 41 (55.4%) were treated with surgery. We did|Conclusions: As expected, patients with older age and lower SMG have higher mortality after|Conclusions: As expected, patients with older age and lower SMG have higher mortality after|Conclusions: As expected, patients with older age and lower SMG have higher mortality after|Conclusions: As expected, patients with older age and lower SMG have higher mortality after|Conclusions: As expected, patients with older age and lower SMG have higher mortality after|

|not find a difference in overall survival between the surgical group (CRT+S) and the|esophagectomy compared to younger patients with higher SMG. Patients who are .75 years|esophagectomy compared to younger patients with higher SMG. Patients who are .75 years|esophagectomy compared to younger patients with higher SMG. Patients who are .75 years|esophagectomy compared to younger patients with higher SMG. Patients who are .75 years|esophagectomy compared to younger patients with higher SMG. Patients who are .75 years|

|group treated with CRT alone (p=0.34). The median survival was 27.4mo (95% CI 15.8, 32.9) in the CRT group compared to 23.0mo (95% CI 14.7, 54.4) in the CRT+S group.|old and in the bottom SMG quartile represent a small group (27/388 = 7% of the total) which are identified as a high-risk group with a mortality of 33.3%. This study identifies a small|old and in the bottom SMG quartile represent a small group (27/388 = 7% of the total) which are identified as a high-risk group with a mortality of 33.3%. This study identifies a small|old and in the bottom SMG quartile represent a small group (27/388 = 7% of the total) which are identified as a high-risk group with a mortality of 33.3%. This study identifies a small|old and in the bottom SMG quartile represent a small group (27/388 = 7% of the total) which are identified as a high-risk group with a mortality of 33.3%. This study identifies a small|old and in the bottom SMG quartile represent a small group (27/388 = 7% of the total) which are identified as a high-risk group with a mortality of 33.3%. This study identifies a small|

||||Age < 75|Age > 75|Total|

|||High Risk: SMG Q1|7/73 (9.6%)|9/27 (33.3%)|100|

|||Low Risk: SMG Q234|6/270 (2.2%)|1/18 (5.6%)|288|

|||CheckMate 649. First Author: Kohei Shitara, National Cancer Center Hospital East,|CheckMate 649. First Author: Kohei Shitara, National Cancer Center Hospital East,|CheckMate 649. First Author: Kohei Shitara, National Cancer Center Hospital East,|CheckMate 649. First Author: Kohei Shitara, National Cancer Center Hospital East,|CheckMate 649. First Author: Kohei Shitara, National Cancer Center Hospital East,|

|||received systemic chemotherapy as an initial treatment. The distant metastatic sites in|received systemic chemotherapy as an initial treatment. The distant metastatic sites in|received systemic chemotherapy as an initial treatment. The distant metastatic sites in|received systemic chemotherapy as an initial treatment. The distant metastatic sites in|received systemic chemotherapy as an initial treatment. The distant metastatic sites in|

|||para-aortic lymph nodes/extra regional mediastinal lymph nodes/lung/liver/bone/others|para-aortic lymph nodes/extra regional mediastinal lymph nodes/lung/liver/bone/others|para-aortic lymph nodes/extra regional mediastinal lymph nodes/lung/liver/bone/others|para-aortic lymph nodes/extra regional mediastinal lymph nodes/lung/liver/bone/others|para-aortic lymph nodes/extra regional mediastinal lymph nodes/lung/liver/bone/others|

|||were 81(54%)/19 (13%)/14 (9%)/11 (7%)/4 (3%)/20 (14%), respectively. After the initial|were 81(54%)/19 (13%)/14 (9%)/11 (7%)/4 (3%)/20 (14%), respectively. After the initial|were 81(54%)/19 (13%)/14 (9%)/11 (7%)/4 (3%)/20 (14%), respectively. After the initial|were 81(54%)/19 (13%)/14 (9%)/11 (7%)/4 (3%)/20 (14%), respectively. After the initial|were 81(54%)/19 (13%)/14 (9%)/11 (7%)/4 (3%)/20 (14%), respectively. After the initial|

|||treatment, 116 patients underwent surgery and 33 patients received CRT as conversion|treatment, 116 patients underwent surgery and 33 patients received CRT as conversion|treatment, 116 patients underwent surgery and 33 patients received CRT as conversion|treatment, 116 patients underwent surgery and 33 patients received CRT as conversion|treatment, 116 patients underwent surgery and 33 patients received CRT as conversion|

|Of the included studies, 38 (51%) were single arm trials, 35 (47%) were randomized trials,|therapy. Of 116 patients who underwent conversion surgery, the incidence rate of|therapy. Of 116 patients who underwent conversion surgery, the incidence rate of|therapy. Of 116 patients who underwent conversion surgery, the incidence rate of|therapy. Of 116 patients who underwent conversion surgery, the incidence rate of|therapy. Of 116 patients who underwent conversion surgery, the incidence rate of|therapy. Of 116 patients who underwent conversion surgery, the incidence rate of|

|and 2 (3%) were non-randomized trials of multiple treatments. Geographically, 28 (37%),|postoperative pneumonia/leakage/recurrent laryngeal nerve palsy was 16%/7%/6%,|postoperative pneumonia/leakage/recurrent laryngeal nerve palsy was 16%/7%/6%,|postoperative pneumonia/leakage/recurrent laryngeal nerve palsy was 16%/7%/6%,|postoperative pneumonia/leakage/recurrent laryngeal nerve palsy was 16%/7%/6%,|postoperative pneumonia/leakage/recurrent laryngeal nerve palsy was 16%/7%/6%,|postoperative pneumonia/leakage/recurrent laryngeal nerve palsy was 16%/7%/6%,|

|24 (32%), 21 (28%), and 2 (3%) of the included trials were performed in Asia, Europe,|respectively. R0 resection was obtained in 87%. Regarding the non-hematological|respectively. R0 resection was obtained in 87%. Regarding the non-hematological|respectively. R0 resection was obtained in 87%. Regarding the non-hematological|respectively. R0 resection was obtained in 87%. Regarding the non-hematological|respectively. R0 resection was obtained in 87%. Regarding the non-hematological|respectively. R0 resection was obtained in 87%. Regarding the non-hematological|

|North America, and Australia, respectively. Across 91 trial arms that delivered either|toxicities during conversion CRT (CTCAE grade 3 or higher), decreased appetite/|toxicities during conversion CRT (CTCAE grade 3 or higher), decreased appetite/|toxicities during conversion CRT (CTCAE grade 3 or higher), decreased appetite/|toxicities during conversion CRT (CTCAE grade 3 or higher), decreased appetite/|toxicities during conversion CRT (CTCAE grade 3 or higher), decreased appetite/|toxicities during conversion CRT (CTCAE grade 3 or higher), decreased appetite/|

|neoadjuvant chemotherapy or chemoradiation, platinum and fluorouracil-based regi-|dysphagia/esophagitis was 21%/15%/9%, respectively. No grade 4 or higher hemato-|dysphagia/esophagitis was 21%/15%/9%, respectively. No grade 4 or higher hemato-|dysphagia/esophagitis was 21%/15%/9%, respectively. No grade 4 or higher hemato-|dysphagia/esophagitis was 21%/15%/9%, respectively. No grade 4 or higher hemato-|dysphagia/esophagitis was 21%/15%/9%, respectively. No grade 4 or higher hemato-|dysphagia/esophagitis was 21%/15%/9%, respectively. No grade 4 or higher hemato-|

|mens were the most common (48.4%), followed by platinum and taxane-based regimens|logic toxicities were observed. The 3-year OS (3y-OS) rate for all patients was 41.9%; no|logic toxicities were observed. The 3-year OS (3y-OS) rate for all patients was 41.9%; no|logic toxicities were observed. The 3-year OS (3y-OS) rate for all patients was 41.9%; no|logic toxicities were observed. The 3-year OS (3y-OS) rate for all patients was 41.9%; no|logic toxicities were observed. The 3-year OS (3y-OS) rate for all patients was 41.9%; no|logic toxicities were observed. The 3-year OS (3y-OS) rate for all patients was 41.9%; no|

|(26.4%), regimens that contained platinum-based agents, fluorouracil, and a taxane|significant differences were found between surgery and CRT groups (43.3% vs 37.0%, p =|significant differences were found between surgery and CRT groups (43.3% vs 37.0%, p =|significant differences were found between surgery and CRT groups (43.3% vs 37.0%, p =|significant differences were found between surgery and CRT groups (43.3% vs 37.0%, p =|significant differences were found between surgery and CRT groups (43.3% vs 37.0%, p =|significant differences were found between surgery and CRT groups (43.3% vs 37.0%, p =|

|(13.2%), and other regimens (12.1%). The pooled prevalence of pCR after neoadjuvant chemotherapy in squamous cell carcinomas was 9% (95% CI: 6% -14%) across 16 studies, ranging from 8% to 66%. For adenocarcinomas, the pooled prevalence of pCR moradiation in squamous cell carcinomas was 32% (95% CI: 26% -39%) across 21 studies, ranging from 0%-32%. The pooled prevalence of pCR after neoadjuvant che-|HR (95% CI) mOS (95% CI) mo Efficacy 0.112). Pathological responders showed a significantly longer OS than non-responders 0.70 (0.61-0.81) 0.79 (0.71-0.88) 14.4 (13.1-16.2) 11.1 (10.1-12.1) 13.7 (12.4-14.5) 11.6 (10.9-12.5) (n = 473) (n = 482) (n = 789) (n = 792) PD-L1 CPS ‡ 5 All randomized NIVO + chemo Chemo NIVO + chemo Chemo (3y-OS, 56.4% vs 36.||||||

|was 2% (95% CI: 0% -7%) after neoadjuvant chemotherapy, across 3 studies, and 22%|48-mo OS rate (95% CI) % mPFS a (95% CI) mo|17 (14-21) 8.3 (7.0-9.3)|8 (6-11) 6.1 (5.6-6.9)|13 (11-16) 7.7 (7.1-8.6)|8 (6-10) 6.9 (6.7-7.2)|8 (6-10) 6.9 (6.7-7.2)|

|||HR (95% CI) ORR a,b (95% CI) % mDuration of response a,c (95% CI) mo|0.71 (0.61-0.82) 60 (55-65) 45 (40-50) 9.6 (8.3-12.4) 7.0 (5.7-8.0)|0.80 (0.71-0.89) 58 (54-62) 46 (42-50) 8.5 (7.7-9.9) 6.9 (5.9-7.6)|||

|307|Poster Session|304 308|||Poster Session Poster Session|Poster Session Poster Session|

|||||||8 cm)|

|||type 3 or type 4 gastric cancer; and age between 20 and 80 years old. Treatment included|type 3 or type 4 gastric cancer; and age between 20 and 80 years old. Treatment included|type 3 or type 4 gastric cancer; and age between 20 and 80 years old. Treatment included|type 3 or type 4 gastric cancer; and age between 20 and 80 years old. Treatment included|type 3 or type 4 gastric cancer; and age between 20 and 80 years old. Treatment included|

|||three cycles of preoperative CapeOx (capecitabine; 2,000 mg/m 2 for 14 days, oxaliplatin;|three cycles of preoperative CapeOx (capecitabine; 2,000 mg/m 2 for 14 days, oxaliplatin;|three cycles of preoperative CapeOx (capecitabine; 2,000 mg/m 2 for 14 days, oxaliplatin;|three cycles of preoperative CapeOx (capecitabine; 2,000 mg/m 2 for 14 days, oxaliplatin;|three cycles of preoperative CapeOx (capecitabine; 2,000 mg/m 2 for 14 days, oxaliplatin;|

|Comparing primary and secondary surgery, the respective LNM rates were 23.5% and|130 mg/m 2 day 1) every 3 weeks, followed by five cycles of postoperative CapeOx after|130 mg/m 2 day 1) every 3 weeks, followed by five cycles of postoperative CapeOx after|130 mg/m 2 day 1) every 3 weeks, followed by five cycles of postoperative CapeOx after|130 mg/m 2 day 1) every 3 weeks, followed by five cycles of postoperative CapeOx after|130 mg/m 2 day 1) every 3 weeks, followed by five cycles of postoperative CapeOx after|130 mg/m 2 day 1) every 3 weeks, followed by five cycles of postoperative CapeOx after|

|26.5%, 6-year OS 78.0% and 89.7%, P= 0.15; DSS were 80.4% and 96.8%, P= .057; and|radical gastrectomy. The primary endpoint was response rate according to the RECIST|radical gastrectomy. The primary endpoint was response rate according to the RECIST|radical gastrectomy. The primary endpoint was response rate according to the RECIST|radical gastrectomy. The primary endpoint was response rate according to the RECIST|radical gastrectomy. The primary endpoint was response rate according to the RECIST|radical gastrectomy. The primary endpoint was response rate according to the RECIST|

|RFS 80.8% and 89.7%, P= .069. Multivariate analyses revealed no statistically significant|v1.0. The planned sample size was 30 patients calculated on the hypothesis that the|v1.0. The planned sample size was 30 patients calculated on the hypothesis that the|v1.0. The planned sample size was 30 patients calculated on the hypothesis that the|v1.0. The planned sample size was 30 patients calculated on the hypothesis that the|v1.0. The planned sample size was 30 patients calculated on the hypothesis that the|v1.0. The planned sample size was 30 patients calculated on the hypothesis that the|

|). 1-year PFS rate was differences between among LNM, OS, and RFS rates. Comparing the adverse events|expected response rate was 65% and the threshold was 50%, with one-sided alpha of|expected response rate was 65% and the threshold was 50%, with one-sided alpha of|expected response rate was 65% and the threshold was 50%, with one-sided alpha of|expected response rate was 65% and the threshold was 50%, with one-sided alpha of|expected response rate was 65% and the threshold was 50%, with one-sided alpha of|expected response rate was 65% and the threshold was 50%, with one-sided alpha of|

o nausea or vomiting|16 (44)|61 (43)|38 (45)|27 (54)|14 (56)|||

|379 Methods: A total of 787 oesophageal carcinoma [adenocarcinoma (EAC), N=604; Poster Session squamous cell carcinoma (ESCC), N=183] were analyzed using next-generation se-quencing (NGS) and immunohistochemistry (Caris Life Sciences, Phoenix, AZ). Tumor mutational burden (TMB) was calculated based on somatic nonsynonymous mutations, and mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) status was evaluated by a combination of IHC, 380 Poster Session 381 Poster Session Dysbiosis in gastric mucosal microbiota associated with gastric carcinogenesis. First Author: Byung-Wook Kim, The Catholic University of Korea, Incheon, South Korea micronuclei DNA (mnDNA) in erythrocytes from peripheral blood. Here, we evaluated the potential of mnDNA for early-stage GI cancer detection, including colorectal (CC) and gastric (GC) cancers. Methods: Peripheral blood (1 ml) was collected from healthy donors (HD) and cancer patients mnDNA isolation and purification from erythrocytes. Participants were randomly divided into training, validation and independent test co-horts in a 7:2:1 ratio, maintaining similar cancer types, CC/GC/HD ratio, gender and age distribution. Distinct mnDNA features between cancer patients and HDs were identified using sequencing data. Logistic regression algorithms were applied using these features for cancer detection. Results: The study enrolled 1046 participants, including 419 HDs, 366 CC and 261 GC cases. Of these, over half were diagnosed with early-stage diseases; TNM stage I accounted for 38.7%, stage II for 22.8%, stage III for 30.5% and stage IV for 8.0%. The cancer detection model with mnDNA features yielded an overall accuracy of 84.8%, with a sensitivity of 84.1% and specificity of 85.7%. For individual caner types, sensitivity was 89.2% for CC and 76.9% for GC. For early-stage (stage I-II) CC and GC, the model demonstrated sensitivities of 88.9% and 76.5%, respectively, at 85.7% specificity. Poster Session Effect of sitravatinib combined with PD-1 blockade on cytotoxic T-cell infiltration by M2 to M1 tumor macrophage repolarization in esophageal adenocarcinoma. First Author: Ashten Omstead, Allegheny Health Network Cancer Institute, Allegheny Health Network, Pittsburgh, PA Conclusions: 383 Background: Methods: End-to-side esophagojejunostomy was performed on a cohort of 96 rats to induce gastro-esophageal reflux, leading to EAC carcinogenesis. At 32 weeks post-operative, all surviving animals underwent endoscopic examination with biopsy and a pre-treatment MRI. All tumor bearing animals were randomized to a dose of 10mg/kg of sitravatinib (S) or vehicle control (VC) for three cycles, and PD-1 inhibitor, AUNP-12 (IO), was administered on day 12 of each 14 day cycle, at a dose of 3mg/kg. At 38 weeks post-operative, animals received a post-treatment MRI and were euthanized. Safety and efficacy were evaluated by on-treatment mortality, pre-and post-treatment MRI, immunohistochemistry, immunofluorescence and real-time PCR. Results: The S+/-IO groups demonstrated a higher on-treatment mortality when compared to the VC+/-IO groups (p=,0.001). Pre-to post-treatment, mean MRI tumor volume decreased by 32% and 73% in the S-IO and S+IO animals and increased by 90% and 160% in the VC+IO and VC-IO animals, respectively (p=,0.001). Increased apoptosis and decreased proliferation were confirmed through Cas-3 and Ki-67 immunohistochemistry, respectively, in both S treatment groups (p=,0.001). CD8+ T-cell infiltration was upre-gulated, and M2 to M1 macrophage phenotype repolarization was demonstrated in all treatment groups by immunofluorescence (p,0.01). Downstream gene expression dem-onstrated upregulation of pro-inflammatory cytokines including TNF-a, IFN-g, IL-1b, IL-6, IL-12 and downregulation of anti-inflammatory cytokines including TGF-b, IL-4, IL-10, and IL-13 in S treatment groups compared to VC treatment groups (p,0.05). There was no significant difference in pre-treatment PD-L1 levels between any of the treatment groups (p=0.09). Pre-to post-treatment qRT-PCR demonstrated significant inhibition of pathway genes AXL, AKT, MERTK and PI3K in the treatment animals (p=,0.001). Additionally, pre-Background: We have developed a method (WO2021/228246 A1) for purifying and characterizing treatment AXL and PD-L1 levels were significantly higher in major responders (.80% tumor| |---|

|(0.62→0.049), SNU-484(2.25-.0.38)). In the dose-finding part of the clinical study, 26|

|patients were enrolled, 13 had received two prior treatments and 13 had received three prior|

|treatments. At data cut-off, median duration of follow-up (range) was 4.4 (1.3 -23.7)|

|months. Of the 26 patients enrolled, 5 (1 BRCA2m and 4 ATMm) had HRD (19.2%) and were|

|treated with varying doses of irinotecan and venadaparib. In the five patients with HRD, an|

||||||387|Poster Session| |---|---|---|---|---|---|---|

||||||Proportion and distribution of PD-L1 expression and associated clinico-|Proportion and distribution of PD-L1 expression and associated clinico-|

||||||pathologic features in patients with microsatellite instability-high gastric|pathologic features in patients with microsatellite instability-high gastric|

|NO LIMIT (WJOG13320G/CA209-7W7) is a phase II trial of nivolumab plus low-dose ipilimumab (NIVO+IPI) for MSI-H advanced gastric or esoph-agogastric junction cancer (GC) in the first-line setting. 1 Here, we investigated the rela-tionship between the number of positive MSI markers and the efficacy of NIVO+IPI in NO LIMIT study. Methods: Eligible patients were unresectable advanced, recurrent, or meta-static GC with confirmed as MSI-H with the MSI-IVD Kit (FALCO), where two or more of the five MSI markers are defined as positive. Nivolumab (240 mg) biweekly and ipilimumab (1 mg/kg) every six weeks were given until disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR) assessed by a blinded independent central review. Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and the association between number of positive MSI markers and clinical efficacy (ORR, PFS, OS). The analysis was performed 18 weeks after the first dose in the last patient, with a median follow-up of 9 months (range, 4.0-18.0). Results: The breakdown of MSI markers in the 29 patients enrolled in NO LIMIT was as follows: BAT-26 (26/26, 100%), NR-21 (25/29, 86.2%), BAT-25 (25/29, 86.2%), MONO-27 (29/29, 100%), NR-24 (27/29, 89.4%). Since most of the cases were positive for all five of them (the number of cases with 2, 3, 4, and 5 positive markers was 2, 2, 1, and 24, respectively), we dichotomized cases into group A (all five positive) and group B (the others). Response rates in groups A vs. B were 62.5% (15/24) vs. 60.0% (3/5), respectively. Group A Group B All|cancer. Methods:The study consists of 847 cases of unselected GC. MSI analysis was performed on all GC cases by im-munohistochemistry for mismatch repair proteins followed by multiplex polymerase chain reaction. Among them, 72 GCs were found to be an MSI-H phenotype. After matching the T category of GCs, 200 cases of GC with MSS phenotype were selected for a control group. Immunohistochemistry for PD-L1 (SP263) was performed on 72 MSI-H GCs and 200 MSS GCs. Results: Patients with MSI-GC were significantly associated with advanced age (p ,0.001), advanced tumor (p=0.0173), antral location of the tumor(p=0.0018), and T2 and T3 category (p=0.0031) but not T1 or T4 category. Histologically, MSI-H GCs occurred frequently in ulcerofungating mass (45.8%, p , 0.0001)), intestinal type (73.6%, p=0.0102), well to moderately differentiated tumor (56.9%, p=0.0102), tubular histologic type (66.7%, p=0.0013), tumor necrosis (18.1%, p ,0.0001), and peritumoral neutrophilic infiltrate (40.3%, p ,0.001) compared to those of 200 MSS GCs. In the evaluation of PD-L1, 55 (76.4%) MSI-H tumors revealed PD-L1 expression with $ 1 CPS. The predominant PD-L1 staining was found in intratumoral and peritumoral immune cells (66.7%) than within tumor cells (9.7%). The distribution of positive immune cells was predominantly located in the periphery of the tumor (37.5%) than within the tumor (9.7%). According to the criteria for PD-L1 positivity as at least 10 CPS, approximately 50% of MSI-H GCs were considered PD-L1 positive tumors with at least 10 CPS. Conclusions: In this study, the prevalence of MSI-H phenotype is ap-proximately 8.5% of unselected GCs. Approximately 76% of patients with MSI-H tumors showed PD-L1 expression with at least 1 CPS, and 50% revealed PD-L1 expression with at least 10 CPS, who can respond better to immune checkpoint inhibitors with promising||||||

|||(N=24)|(N=5)|(N=29)|||

|Number of Responders|n (%)|15 (62.5%)|3 (60.0%)|18 (62.1%)|||

|Complete Response (CR)|n (%)|2 (8.3%)|1 (20.0%)|3 (10.3%)|||

|Partial Response (PR)|n (%)|13 (54.2%)|2 (40.0%)|15 (51.7%)|||

|Stable Disease (SD)|n (%)|4 (16.7%)|1 (20.0%)|5 (17.2%)|||

|Progressive Disease (PD)|n (%)|3 (12.5%)|1 (20.0%)|4 (13.8%)|||

|Not evaluated (NE)|n (%)|2 (8.3%)|0 (0.0%)|2 (6.9%)|||

||||||Increased||

||||||expression of EMT was seen in Group A and B, indicating they are likely to have|expression of EMT was seen in Group A and B, indicating they are likely to have|

||||||metastasis. Group B showed worse PFS than others (13.8 M in A, 7.0 M in B and not|metastasis. Group B showed worse PFS than others (13.8 M in A, 7.0 M in B and not|

||||||reached in C, p=0.012), suggesting Group B could be a candidate for expand indication of|reached in C, p=0.012), suggesting Group B could be a candidate for expand indication of|

||||||Trastuzumab. Genomic analysis showed some mutated genes involved in the PI3K|Trastuzumab. Genomic analysis showed some mutated genes involved in the PI3K|

||||||signaling pathway which associated with drug resistance. Conclusions: Monitoring of|signaling pathway which associated with drug resistance. Conclusions: Monitoring of|

||||||circulating tumor cells leads to the expand indication of the HER2 targeted therapies in|circulating tumor cells leads to the expand indication of the HER2 targeted therapies in|

||||||patients with metastatic gastric cancer. Research Sponsor: None.||

|96s|ESOPHAGEAL AND GASTRIC CANCER||||||| |---|---|---|---|---|---|---|---|

|||395||||Poster Session||

|Methods: We analyzed tissue and blood samples from 496 patients who underwent|||||Successful induction of|||

|gastrectomy for gastric cancer and participated in the Project HOPE (High-tech Omics-|hypoxia was confirmed by 2',7' -dichlorofluorescein diacetate (DCFDA) assay by de-|||||||

|based Patient Evaluation) in our hospital, from 2014 to 2019. We excluded patients with|tection of cellular reactive oxygen species (ROS). 7-Dimethylaminoethylamino-17-|||||||

|other special types of gastric cancer, remnant gastric cancer and preoperative che-|demethoxygeldanamycin (17-DMAG), a selective Hsp90 inhibitor, was used to treat 2|||||||

|motherapy. We analyzed gene mutation, copy number, and gene expression between 10|ESCC cell lines, KYSE-170 and -510 cells pretreated with or without CoCl2, an agent to|||||||

|HAD/ACED and 486 common types of gastric cancers. Results: The mutated genes with|induce a hypoxic tumor microenvironment. Cytotoxicity (MTT) and migration assays|||||||

|high frequency (. 20%) in HAD/ACED were TP53 (100%) CSMD3 (30%), LRP1B, FAT3,|were conducted in KYSE-17 and -510 ESCC cells in response to different concentrations|||||||

|TG, APOB, CREBBP, PASK, DROSHA and STK40 (20%). The tumor mutation burden (TMB)|of CoCl2, followed by protein expression of Hsp 90, vascular endothelial growth factor|||||||

|of all the cases were less than 10. TMB of HAD/ACED was equivalent to that of common|(VEGF), hypoxia-inducible factor-1a (HIF-1a), mTOR as well as markers related|||||||

|type of gastric cancer with microsatellite stable type. The copy number of 20q13.2|epithelial-mesenchymal transition (EMT) such as snail or E-cadherin, by immunoblot or|||||||

|encoding SALL4 was significantly gained in HAD/ACED (p = 0.03). Furthermore, 17|ELISA. In parallel, cell proliferation and migration assays of ESCC cells were analyzed.|||||||

|genes were highly expressed in these tumors, and many of these genes were associated|Results: CoCl2 induced hypoxia was supported by an induction of reactive oxygen|||||||

|with hepatocytes and fetal organs, including LIN28B, IGF2BP1, and HMGA2, which are|species (ROS). CoCl2 (200 mM) significantly suppressed cell viability and proliferation|||||||

|related to TP53 mutation. Conclusions: Our molecular profiling revealed similarities|with a concomitant up-regulation of VEGF and HIF-1a in a dose-dependent fashion. In|||||||

|between HAD/ACED and hepatocytes/fetal organs and high expression of LIN28B,|contrast, cell migration was significantly increased in response to CoCl2, while down-|||||||

|IGF2BP1 and HMGA2, which are associated with TP53 inactivation. These results|regulating E-cadherin with concomitant increase in Snail expression. 17-DMAG de-|||||||

|suggest that these genes may define morphological features of HAD/ACED. Research|creased expression of VEGF and HIF-1a. In addition, it inhibited cell migration and|||||||

|Sponsor: None.||invasion of ESCC cells were analyzed. Conclusions:|invasion of ESCC cells were analyzed. Conclusions:|invasion of ESCC cells were analyzed. Conclusions:|invasion of ESCC cells were analyzed. Conclusions:|invasion of ESCC cells were analyzed. Conclusions:|invasion of ESCC cells were analyzed. Conclusions:|

||||||First Author: Henian Sun, Pirogov Russian|||

|||National Research Medical University, Moscow, Russian Federation|National Research Medical University, Moscow, Russian Federation|National Research Medical University, Moscow, Russian Federation|National Research Medical University, Moscow, Russian Federation|National Research Medical University, Moscow, Russian Federation|National Research Medical University, Moscow, Russian Federation|

|||Background: GC is a heterogeneous disease with a range of molecular subtypes. The||||||

|||TCGA (Cancer Genome Atlas) and ARCG (Asian Cancer Research Group) classified||||||

|||tumors with MSI status as a specific group. Programmed cell death receptor 1 (PD-1)||||||

|||and its ligand (PD-L1) are playing a progressively important role in tumor immunology||||||

|||and cancer treatment. The present study investigated the relationship between MSI and||||||

|||PD-L1 expression. Methods: We analyzed GC patients who received treatment from||||||

|||September 2019 to March 2023 at N.N. Blokhin National Medical Research Center of||||||

|||Oncology. All patients were analyzed for microsatellite instability using PCR. PD-L1||||||

|||expression was assessed based on a combined positive score (CPS) using PD-L1 IHC||||||

|||(immunohistochemistry) 22C3 pharmDx. Results: We studied 453 localized GC and 273||||||

|||metastatic GC. Of the 726 tumors, 60 (8.26%) had MSI-H tumors. The frequency of MSI-H||||||

|||in localized and metastatic GC is 51 (11.26%) out of 453 and 9 (3.30%) out of 273||||||

|||(p,0.001). 106 patients were evaluated for expression PD-L1, 46 (43.40%) localized GC||||||

|||j 60 (56.60%) metastatic GC. PD-L1 is expressed in 45.28 % (48/106) of GC patients. PD-||||||

|||L1 CPS $ 1 was significantly associated with MSI-H status (P , 0.05). Details about the||||||

|||correlation between MSI and the expression PD-L1 can be found in the table.||||||

|||Conclusions: The prevalence of MSI-H in localized GC is significantly higher than||||||

|||metastatic GC (11.26% vs. 3.30%, p,0.001). A higher proportion showed PD-L1 ex-||||||

|||pression (73.91%) in MSI-H than in MSS tumors, suggesting that MSI-H status is as-||||||

|||sociated with PD-L1 (p, 0.05). These results provide a basis for identifying GC patients||||||

|||who may benefit from anti-PD-1/PD-L1 therapy. Research Sponsor: None.||||||

|||Correlation MSI with expression PD-L1 (CPS).||||||

||||Total|PD-L1(CPS)|1£PD-L1|5 < PD-L1|PD-L|

||||Patients|Negative|(CPS) £5|(CPS) £10|(CPS) > 10|

|||MSS|83|42 (50.6%)|17 (20.48%)|4 (4.82%)|20 (24.10%)|

|||MSI-H|23|6 (26.09%)|5 (21.74%)|5 (21.74%)|7 (30.43%)|

|400|Poster Session| |---|---|

|Methods: The Screening Projectfor Individualized Medicine in Japan (J-SCRUM) GI-|Methods: The Screening Projectfor Individualized Medicine in Japan (J-SCRUM) GI-|

|SCREEN enrolled advanced GI cancer patients from 26 sites before planned or during|SCREEN enrolled advanced GI cancer patients from 26 sites before planned or during|

|systemic therapy from 2015 to 2019. Archived formalin-fixed paraffin-embedded tumor|systemic therapy from 2015 to 2019. Archived formalin-fixed paraffin-embedded tumor|

|tissue was analyzed by next-generation sequencing (NGS) using Oncomine Cancer|tissue was analyzed by next-generation sequencing (NGS) using Oncomine Cancer|

|Research Panel and Oncomine Comprehensive Assay. Patients with gastric (GC),|Research Panel and Oncomine Comprehensive Assay. Patients with gastric (GC),|

|complications compared to LG. Long-term survival outcomes should be investigated.|patients in D2 group and three (27%) patients in D2+PAND group, and lymph node|patients in D2 group and three (27%) patients in D2+PAND group, and lymph node||||||

|Research Sponsor: None.|||||recurrence was observed in four (40%), and one (10%) patients, respectively. The|recurrence was observed in four (40%), and one (10%) patients, respectively. The||

|||||||D2+PAND group had significantly better overall survival, recurrence-free survival, and|D2+PAND group had significantly better overall survival, recurrence-free survival, and|

|Cancer Staging Manual, 7 (58.3%) were classified as stage II, and 5 (41.7%) were| |---|

|classified as stage III. As of the data cut-off date (August 25, 2023), the median follow-up|

|time was 5.1 months (95% CI: 3.4-6.8). 2 pts experienced disease recurrence, and the|

|median duration of DFS has not yet been reached. Currently, 9 pts are still undergoing|

|therapy, with treatment durations ranging from 0.3 months to 9.6 months. 2 pts dis-|

|continued therapy due to adverse events (AE), which subsequently improved after|

|treatment. One patient experienced immune-related myocarditis, while the other patient|

|||). Safety set included all 52|| |---|---|---|---|

|patients. Any grade adverse events (AEs) were reported in 90.4% (n=47) of the patients; with 40.4%||||

|experiencing grade 3/4 AEs. All-grade AEs reported in $10% of the patients included anemia,||||

|neutropenia, abdominal pain, diarrhea, nausea, vomiting, fatigue, mucositis, decreased appetite,||||

|peripheral neuropathy; with majority of AEs being grade 1/2. Most common grade 3/4 AE was||||

|neutropenia; observed in 17.3% (n=9) patients (mDCF: 14%; DCF: 33.3%). Conclusions: NDLS-based||||

|regimens demonstrated efficacy & improved safety profile in the treatment of metastatic GAC.||||

|Clinical trial information: CTRI/2018/01/011450. Research Sponsor: Intas Pharmaceuticals Limited,||||

|Ahmedabad, Gujarat, India.||||

|Efficacy outcomes.||||

||mITT population|||

|CR, n (%)|1 (2.6)|1 (3.0)|0 (0)|

|PR, n (%)|21 (55.3)|18 (54.5)|3 (60)|

|SD, n (%)|9 (23.7)|8 (24.2)|1 (20)|

|ORR, n (%) [95% CI]|22 (57.9) [40.8, 73.7] 19 (57.6) [39.2, 74.5] 3 (60) [14.7, 94.7]|||

|DCR, n (%) [95% CI]|31 (81.6) [65.7, 92.2] 27 (81.8) [64.5, 93] 4 (80) [28.3, 99.5]|||

|Median PFS (months), [95% CI]|8.4 [5.6, 9.1]|9 [5.1, 9.1]|8.1 [1.9, NE]|

|Median OS (months)|NR|NR|NR|

|352|Poster Session| |---|---|

|Neoadjuvant anlotinib combined with penpulimab for resectable locally|Neoadjuvant anlotinib combined with penpulimab for resectable locally|

|advanced esophageal squamous cell carcinoma (ESCC): A prospective,|advanced esophageal squamous cell carcinoma (ESCC): A prospective,|

|single-arm, phase II trial. First Author: yueyun chen, Department of Biotherapy,|single-arm, phase II trial. First Author: yueyun chen, Department of Biotherapy,|

|Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan|Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan|

|University, Chengdu, China||

|Median age was 63 years (range: 28, 78), with 30 pts (83.3%) were male. 13 pts (36.1%)||

|presented with GEJ. 34 pts (94.5%) were diagnosed with stage IV. 20 pts (55.6%) had distant||

|lymph node involvement, 18 (50.0%) had liver metastasis, 8 (22.2%) had peritoneal metastasis,||

|and 2 (5.6%) had lung metastasis. Median serum AFP level was 739.8 ng/ml (range: 77.7,||

|321847.0). At data cut-off (Sep 1, 2023), the median follow-up duration was 6.4 months (range:||

|0.7, 27.0). Efficacy was assessed in the FAS population (n = 36). 2 pts showed complete||

|response (CR, all confirmed), 22 had partial response (PR, 18 confirmed) and 7 had stable||

|disease (SD). In consequent, the unconfirmed ORR was 66.7% (24/36) and DCR was 86.1% (31/||

|36), with a confirmed ORR of 55.6% (20/36). The median PFS and OS were still immature.||

|However, the estimated 12-month PFS rate was 42.1%. Any grade treatment-related adverse||

||||||||354|Poster Session||| |---|---|---|---|---|---|---|---|---|---|---|

||||||||Efficacy results.||||

|||||||||Group A|Group B|Group C|

|||||||||(n=18)|(n=17)|(n=18)|

||||||||Median PFS, months (95% CI)|15.1 (6.8, NE)|NR (9.9, NE)|8.2 (5.7, 12.7)|

||||||||HR* (95% CI)|0.5 (0.2, 1.3)|0.1 (0.0, 0.5)|-|

|BOR per RECIST v1.1, n (%)|All patients, n=15|Prior IO, n=10|No prior IO, n=5|Confirmed ORR, % (95% CI) ORR at week 36, % (95% CI)|77.8 (52.4, 93.6) 44.4 (21.5, 69.2)|82.4 (56.6, 96.2) 64.7 (38.3, 85.8)|88.9 (65.3, 98.6) 27.8 (9.7, 53.5)||||

|CR PR SD PD ORR, % (95% CI)|0 (0) 5 (33.3) 9 (60.0) 1 (6.7) 33.3 (11.8~61.6)|0 (0) 3 (30.0) 6 (60.0) 1 (10.0) 30.0 (6.7~65.2)|0 (0) 2 (40.0) 3 (60.0) 0 (0) 40.0 (5.3~85.3)|ORR at week 48, % (95% CI) Median OS, months (95% CI) HR* (95% CI) Median DOR, months (95% CI) HR* (95% CI)|38.9 (17.3, 64.3) NR (12.4, NE) 0.4 (0.1, 1.5) 12.4 (5.5, NE) 0.6 (0.2, 1.6)|58.8 (32.9, 81.6) NR (NE, NE) 0.3 (0.1, 1.3) NR (8.6, NE) 0.1 (0.0, 0.5)|16.7 (3.6, 41.4) NR (6.4, NE) -6.8 (4.4, NE) -||||

|DCR, % (95% CI)|93.3 (68.1~99.8)|90.0 (55.5~99.7)|100.0 (47.8~100)||||||||

|mPFS, mo (95% CI)|5.23 (3.67~NA)||5.23 (3.53~NA)|4.77 (3.67~NA)|||||||

|355||||Poster Session|356|Poster Session|||||

|Phase 1b/II study of durvalumab (D) and tremelimumab (T) plus PET-|||||||||||

|adjudicated chemoradiation (CRT) in patients (Pts) with esophageal|||||||||||

|adenocarcinoma. First Author: Geoffrey Yuyat Ku, Memorial Sloan Kettering Can-|||||||||||

|cer Center, New York, NY|||||||||||

|Adverse Event (n=16)|Gd 1|Gd 2|Gd 3||Gd 4||||||

|Anorexia|1 (6%)|6 (38%)|1 (6%)|-|||||||

|Constipation|8 (50%)|-||-||-|||||

|Diarrhea|8 (50%)|3 (19%)|-||-||||||

|Dysphagia|3 (19%)|11 (69%)|-||-||||||

|Esophageal pain|3 (19%)|1 (6%)|-||-||||||

|Fatigue|7 (44%)|2 (13%)|-||-||||||

|Neutropenia|-|1 (6%)|2 (13%)|-|||||||

|Thrombocytopenia|6 (38%)|-||-||-|||||

|Poster Session|359|Poster Session| |---|---|---|

|361|Poster Session| |---|---|

|Results: 156 patients (out of total 334 included in the study) received doublet NCT|Results: 156 patients (out of total 334 included in the study) received doublet NCT|

|(FOLFOX/XELOX, 8/6 cycles respectively), 61.5% were males, median age was 67.4|(FOLFOX/XELOX, 8/6 cycles respectively), 61.5% were males, median age was 67.4|

|(range 21.3-85.4) years, 88.2% had cT3-4. and 22.4% had locally advanced gastro-|(range 21.3-85.4) years, 88.2% had cT3-4. and 22.4% had locally advanced gastro-|

|esophageal junction (GEJ) adenocarcinoma. 177 patients were treated with triple NCT|esophageal junction (GEJ) adenocarcinoma. 177 patients were treated with triple NCT|

|(FLOT, 8 cycles), 62.1% were males, median age was 59.9 years, 89.2% had cT3-4, and|(FLOT, 8 cycles), 62.1% were males, median age was 59.9 years, 89.2% had cT3-4, and|

|locally advanced GEJ adenocarcinoma was diagnosed in 21.0%. At a median follow up of|locally advanced GEJ adenocarcinoma was diagnosed in 21.0%. At a median follow up of|

|34.7 months (mth) using FLOT regimen as NCT was associated with better clinical|34.7 months (mth) using FLOT regimen as NCT was associated with better clinical|

|outcomes. The ratio of patients who have progressed on NCT was 21.5% and 31% in|outcomes. The ratio of patients who have progressed on NCT was 21.5% and 31% in|

|triplet and doublet arms, respectively (p=0.098). Rates of ypN0 were 50.5% in FLOT arm|triplet and doublet arms, respectively (p=0.098). Rates of ypN0 were 50.5% in FLOT arm|

|and 43.7% in XELOX/FOLFOX arm (p=0.36). pCR was achieved in 8.2% and 6.3% in FLOT|and 43.7% in XELOX/FOLFOX arm (p=0.36). pCR was achieved in 8.2% and 6.3% in FLOT|

|and XELOX/FOLFOX arms, respectively (p=0.59). Median PFS was 20.3 mth in FLOT arm|and XELOX/FOLFOX arms, respectively (p=0.59). Median PFS was 20.3 mth in FLOT arm|

|in comparison to 15.7 mth in FOLFOX/XELOX arm (p=0.012). Median OS was not reached|in comparison to 15.7 mth in FOLFOX/XELOX arm (p=0.012). Median OS was not reached|

|(NR) for triplet arm and was 25.1 mth for doublet arm (p= 0.003). Patients who|(NR) for triplet arm and was 25.1 mth for doublet arm (p= 0.003). Patients who|

|conversed resectable disease had median PFS of 34.5 and 23.1 months for FLOT and|conversed resectable disease had median PFS of 34.5 and 23.1 months for FLOT and|

|363|Poster Session| |---|---|

|8%| |---|

|(I),16.4% (II), 69.2% (III), and 5.5% (IVA), respectively. After Neo DCF treatment, 90|

|patients (98.9%) underwent curative surgery. Median DFS and 3-year DFS rate were not|

|reached and 76.9%. The incidence of pathological complete response (pCR) and major|

|pathological response (MPR) were 11.1% (10/90) and 35.6% (32/90), respectively. There|

|were no cases of recurrence in patients with pCR and MPR. The most common grade 3 or|

|4 AEs were neutropenia (58/91, 63.7 %), diarrhea (15/91, 16.5%), and thrombosis (9/91,|

|9.9%), respectively. Febrile neutropenia occurred in 33 patient (36.2%). Clinical T stage|

|was significantly associated with pCR (P = 0.033). Conclusions: Neo DCF was effective|

|and tolerable in the real-world ESCC patients in Japan. Research Sponsor: None.|

|371|Poster Session| |---|---|

|||||||373|Poster Session| |---|---|---|---|---|---|---|---|

|||||||Results: 31 patients were enrolled, with 29 patients evaluable for efficacy. The median|Results: 31 patients were enrolled, with 29 patients evaluable for efficacy. The median|

|||||||age was 61 years (range 32-79). 86% had an ECOG performance status of one. 48%|age was 61 years (range 32-79). 86% had an ECOG performance status of one. 48%|

|||||||had $ 2 prior lines of systemic therapies (range 1-4). Of the 29 pts evaluable for efficacy,|had $ 2 prior lines of systemic therapies (range 1-4). Of the 29 pts evaluable for efficacy,|

|||||||6 pts had confirmed objective responses (5 PR + 1 CR = ORR 20.69%). The most common|6 pts had confirmed objective responses (5 PR + 1 CR = ORR 20.69%). The most common|

|||||||TRAEs were fatigue (65%), anorexia (58%), elevated liver enzymes (39%), and diarrhea|TRAEs were fatigue (65%), anorexia (58%), elevated liver enzymes (39%), and diarrhea|

|||||||(35%). Grade .3 TRAEs occurred in 19% of pts. Grade .3 immune-related adverse|(35%). Grade .3 TRAEs occurred in 19% of pts. Grade .3 immune-related adverse|

|||||||events (irAE) rate was 6%. DCR was 86.2% (25/29). Median PFS and OS were 4.4 (95%|events (irAE) rate was 6%. DCR was 86.2% (25/29). Median PFS and OS were 4.4 (95%|

|||||||confidence interval (CI) 2.2-5.4) and 5.6 months (95% CI 3.6-8.3) respectively. In patients|confidence interval (CI) 2.2-5.4) and 5.6 months (95% CI 3.6-8.3) respectively. In patients|

|||||||with PD-L1 CPS .5 (12/29), ORR was 25%, and median PFS and OS were 5.5 months|with PD-L1 CPS .5 (12/29), ORR was 25%, and median PFS and OS were 5.5 months|

|||181 (65)|121 (43)|69 (25)|32 (11)|(95% CI 1.8-12.4) and 19.3 months (95% CI 2.3-28.2) respectively.||

|||95 (52)|58 (48)|34 (49)|15 (47)|||

|Vomiting|15 (50)|63 (35)|44 (36)|23 (33)|10 (31)|||

|N/V|11 (37)|48 (27)|32 (26)|19 (28)|8 (25)|||

|No nausea or vomiting|10 (33)|71 (39)|51 (42)|31 (45)|15 (47)|||

|GLOW (N = 253), n (%)|36 (14)|143 (57)|85 (34)|50 (20)|25 (10)|||

|Nausea|13 (36)|60 (42)|34 (40)|17 (34)|7 (28)|||

|Vomiting|17 (47)|54 (38)|33 (39)|14 (28)|7 (28)|||

|N/V|10 (28)|32 (22)|20 (24)|8 (16)|3 (12)|||

|No nausea or vomiting|16 (44)|61 (43)|38 (45)|27 (54)|14 (56)|||

|38 and venadaparib exerted synergistic effect with combination indices (CI) ranging from|

|0.013 to 0.991 in SNU-638 (BRCA2m), SNU-668 (BRCA1m), AGS (low ATM) and SNU-484|

|(HR proficient) cells. We observe the synergistic effect between SN-38 and venadaparib|

|remained consistent even at low concentrations of venadaparib (SN-38 IC50; without|

|venadaparib → with 10 nM of venadaparib; SNU-638(1.72→0.28), SNU-668(10.7→1.5), AGS|

ical University, Guangzhou, Guangdong, China Background:| |---|

|25 mg/m 2 on days 1, 8, 15; oxaliplatin 85 mg/m 2 on days 1, 15; fluorouracil 1200 mg/m 2 24-hour||||| |---|---|---|---|---|

|Exclusion Criteria: Treated by a combination regimen containing all the study drugs; allergy to|||||

|any of the study drugs; HER-2 gene overexpression; high microsatellite instability or mismatch|||||

|repair deficiency; strangulated obstruction; active gastrointestinal bleeding; uncontrolled active|||||

|infection; unstable heart diseases; severe lung diseases; central nervous system diseases;|||||

|Cohort A (first-line)|30%|55%|9|26|

|Cohort C (third-or later-line)|10%|35%|8|14|

|||TPS428|Trials in Progress Poster Session| |---|---|---|---|

|A phase I study of EO-3021 in adult patients with solid tumors likely to|SWOG S2303: Randomized phase II/III trial of 2nd line nivolumab + pacli-|SWOG S2303: Randomized phase II/III trial of 2nd line nivolumab + pacli-||

|express CLDN18.2. First Author: Meredith Pelster, Sarah Cannon Research Institute,|taxel + ramucirumab versus paclitaxel + ramucirumab in patients with PD-L1|taxel + ramucirumab versus paclitaxel + ramucirumab in patients with PD-L1||

|Tennessee Oncology, Nashville, TN||CPS ‡ 1 advanced gastric and esophageal adenocarcinoma (PARAMUNE).|CPS ‡ 1 advanced gastric and esophageal adenocarcinoma (PARAMUNE).|

|esophageal (EC) and pancreatic (PC) cancers were identified in the database. The|esophageal (EC) and pancreatic (PC) cancers were identified in the database. The|

|frequency of key actionable genomic alterations in each cancer cohort was explored and|frequency of key actionable genomic alterations in each cancer cohort was explored and|

|compared to similar upper GI cohorts in The Cancer Genome Atlas (TCGA), a publicly|compared to similar upper GI cohorts in The Cancer Genome Atlas (TCGA), a publicly|

|available genomics database initiated in 2005 and concluded sample collection in 2013|available genomics database initiated in 2005 and concluded sample collection in 2013|

] ; percent males: 65%), 265 EC (64y [9]; 78%) and 495 PC (64y|

|404|Poster Session|| |---|---|---|

|(12%) patients, and no correlation was observed between HER2 and CLDN18.2 ex-|||

||61 (18-83)||

|Male -no. (%)|54|53,5|

|Primary site:|96|92,1|

|Gastric, -no. (%)|5|5|

|GEJ, -no. (%)|||

|Stage IV novo -no. (%)|88|87,1|

|Histological|41|40,6|

|Diffuse, -no. (%)|38|37,6|

|Intestinal, -no. (%)|6|5,9|

|Mixed, -no. (%)|||

|Location|76|75,2|

|Distal, -no. (%)|25|24,8|

|No distal, -no. (%)|||

|dMMR -no. (%)|5|5|

|HER2, -no. (%)|5|5|

|Positive, -no. (%)|74|73,2|

|Negative, -no. (%)|22|21,8|

|Unknown, -no. (%)|||

||31|30,6|

||23|22,7|

||30|29,7|

|100s||ESOPHAGEAL AND GASTRIC CANCER|||||||| |---|---|---|---|---|---|---|---|---|---|

|De-risking 1st line chemotherapy-free immune checkpoint inhibitor (ICI) use for patients with advanced gastroesophageal cancer (aGEJ) with tumor mutational burden (TMB). First Author: Samuel J. Klempner, Massachusetts General Hospital, Boston, MA Background: mB would have more favorable outcomes receiving ICI-chemo vs. mono-ICI and (2) patients with TMB $10 mut/mB would have diminished additional benefit from chemo-ICI vs. mono-ICI. Methods: This study included patients with aGEJ who received 1 st line chemo-ICI or mono-ICI and tumor tissue genomic profiling by Foundation Medicine. Patient data was obtained by the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine gastric real-world clinico-genomic database (FH-FMI CGDB), originating from approximately 280 US cancer clinics (January/2011-March/2023). Real-world progression-free survival (rwPFS) and overall survival (rwOS) were compared between patients receiving chemo-ICI vs. mono-ICI by Cox models, adjusted by propensity scores accounting for disease stage at diagnosis, ECOG PS, PD-L1 score and microsatellite instability (MSI) status. Comparisons of the explanatory power of TMB (,10 vs. $10 mut/mB) vs. MSI status (MSI-H vs MSS) were performed by likelihood ratio test (LRT). Results: A total of 263 patients (176 receiving chemo-ICI and 87 mono-ICI) were included in the study. Patients with TMB ,10 mut/mB had more favorable outcomes receiving chemo-ICI vs. mono-ICI for rwPFS (median 5.8 vs. 1.9 months, hazard ratio [HR] : 0.44, 95% confidence interval [CI] 0.26-0.76), p=0.0029) and rwOS (median 11.1 vs. 7.9 months, HR: 0.68, 95% CI 0.40-1.15, p=0.1489). Patients with TMB $10 mut/mB did not have reduced benefit from mono-ICI; curiously less favorable outcomes were observed with chemo-ICI vs. mono-ICI for rwPFS (HR: 3.27, 95% CI 1.19-8.97, p=0.0212) and rwOS (HR: 3.56, 95% CI 1.14-11.08, p=0.0286). Evaluating only the mono-ICI group, the LRT indicated that when TMB was added to a model evaluating only MSI status, there was an improvement in ICI outcome prediction (p=0.006 for rwPFS and p=0.003 for rwOS), but not when MSI was added to TMB (p=0.91 for rwPFS and p=0.40 for rwOS). 408 Methods: Retrospective study included patients from the National Cancer Institute of Poster Session México, with locally advanced gastric adenocarcinoma diagnosis between 2008 and 2017. The Kaplan Meier, Log Rank, and Cox Regression methods were used to analyze the relation between MMR status and overall survival in LAGC. MMR status was assessed using im-munohistochemistry. Results: A total of 103 patients with LACG were enrolled for analysis. The prevalence of dMMR in GC was 13.59% (n=14). The median OS was 101.9 months in the dMMR group vs. 86.2 months in the proficient MMR (pMMR) group (HR 0.54, 95% CI 0.19 -1.52, p=0.23), with a 3-year OS of 71.4% vs 65.1% respectively. Survival was also analyzed according to MMR status and choosing treatment. OS was 106.8 months in the dMMR surgery alone group, 78.4 months in the dMMR group treated with both surgery and chemotherapy, 33.1 months for pMMR group with surgery alone, and 89.2 months in the pMMR group treated with surgery plus chemotherapy (p=0.014). Conclusions: In this analysis, OS tended to improve in dMMR group. pMMR surgery alone patients had a superior OS than other groups, while adding chemotherapy to surgery treatment seems to have a role only in pMMR patients. Research Sponsor: None. Variable Median OS (months) p=value HR (95% IC) Survival according to MMR status dMMR 101.9 p=0.21 0.54 (0.19-1.52) pMMR 86.2 Survival according to MMR status and treatment dMMR + S 106.8 p=0.014* 0.21 (0.05-0.91) dMMR + S/CH 78.4 pMMR + S 33.1||||||||||

||||pMMR + S/CH||89.2|||||

||||406||||||Poster Session|

||||Cell free DNA (cfDNA) assessment of esophagogastric (EG) cancer using|Cell free DNA (cfDNA) assessment of esophagogastric (EG) cancer using|Cell free DNA (cfDNA) assessment of esophagogastric (EG) cancer using|Cell free DNA (cfDNA) assessment of esophagogastric (EG) cancer using|Cell free DNA (cfDNA) assessment of esophagogastric (EG) cancer using|Cell free DNA (cfDNA) assessment of esophagogastric (EG) cancer using|Cell free DNA (cfDNA) assessment of esophagogastric (EG) cancer using|

||||MSK-ACCESS. First Author: Samuel Louis Cytryn, Memorial Sloan Kettering Cancer|MSK-ACCESS. First Author: Samuel Louis Cytryn, Memorial Sloan Kettering Cancer|MSK-ACCESS. First Author: Samuel Louis Cytryn, Memorial Sloan Kettering Cancer|MSK-ACCESS. First Author: Samuel Louis Cytryn, Memorial Sloan Kettering Cancer|MSK-ACCESS. First Author: Samuel Louis Cytryn, Memorial Sloan Kettering Cancer|MSK-ACCESS. First Author: Samuel Louis Cytryn, Memorial Sloan Kettering Cancer|MSK-ACCESS. First Author: Samuel Louis Cytryn, Memorial Sloan Kettering Cancer|

||||Center, New York, NY|||||||

||||||||||patients with EG|

||||adenocarcinoma underwent cfDNA analysis; 18% had esophageal tumors, 44% had GEJ, and|adenocarcinoma underwent cfDNA analysis; 18% had esophageal tumors, 44% had GEJ, and|adenocarcinoma underwent cfDNA analysis; 18% had esophageal tumors, 44% had GEJ, and|adenocarcinoma underwent cfDNA analysis; 18% had esophageal tumors, 44% had GEJ, and|adenocarcinoma underwent cfDNA analysis; 18% had esophageal tumors, 44% had GEJ, and|adenocarcinoma underwent cfDNA analysis; 18% had esophageal tumors, 44% had GEJ, and|adenocarcinoma underwent cfDNA analysis; 18% had esophageal tumors, 44% had GEJ, and|

||||38% had gastric. 78 (80%) patients had cfDNA obtained prior to treatment (48 [50%] metastatic;|38% had gastric. 78 (80%) patients had cfDNA obtained prior to treatment (48 [50%] metastatic;|38% had gastric. 78 (80%) patients had cfDNA obtained prior to treatment (48 [50%] metastatic;|38% had gastric. 78 (80%) patients had cfDNA obtained prior to treatment (48 [50%] metastatic;|38% had gastric. 78 (80%) patients had cfDNA obtained prior to treatment (48 [50%] metastatic;|38% had gastric. 78 (80%) patients had cfDNA obtained prior to treatment (48 [50%] metastatic;|38% had gastric. 78 (80%) patients had cfDNA obtained prior to treatment (48 [50%] metastatic;|

||||29 [30%] locally advanced) and 21 (21%) at time of progression. 85% had matched tumor NGS|29 [30%] locally advanced) and 21 (21%) at time of progression. 85% had matched tumor NGS|29 [30%] locally advanced) and 21 (21%) at time of progression. 85% had matched tumor NGS|29 [30%] locally advanced) and 21 (21%) at time of progression. 85% had matched tumor NGS|29 [30%] locally advanced) and 21 (21%) at time of progression. 85% had matched tumor NGS|29 [30%] locally advanced) and 21 (21%) at time of progression. 85% had matched tumor NGS|29 [30%] locally advanced) and 21 (21%) at time of progression. 85% had matched tumor NGS|

||||performed with MSK IMPACT: median TMB was 5.3 mut/Mb (IQR 3.3-7.4) and median alterations|performed with MSK IMPACT: median TMB was 5.3 mut/Mb (IQR 3.3-7.4) and median alterations|performed with MSK IMPACT: median TMB was 5.3 mut/Mb (IQR 3.3-7.4) and median alterations|performed with MSK IMPACT: median TMB was 5.3 mut/Mb (IQR 3.3-7.4) and median alterations|performed with MSK IMPACT: median TMB was 5.3 mut/Mb (IQR 3.3-7.4) and median alterations|performed with MSK IMPACT: median TMB was 5.3 mut/Mb (IQR 3.3-7.4) and median alterations|performed with MSK IMPACT: median TMB was 5.3 mut/Mb (IQR 3.3-7.4) and median alterations|

||||per tumor sample was 11 (IQR 7-17). cfDNA identified a similar molecular profile compared to|per tumor sample was 11 (IQR 7-17). cfDNA identified a similar molecular profile compared to|per tumor sample was 11 (IQR 7-17). cfDNA identified a similar molecular profile compared to|per tumor sample was 11 (IQR 7-17). cfDNA identified a similar molecular profile compared to|per tumor sample was 11 (IQR 7-17). cfDNA identified a similar molecular profile compared to|per tumor sample was 11 (IQR 7-17). cfDNA identified a similar molecular profile compared to|per tumor sample was 11 (IQR 7-17). cfDNA identified a similar molecular profile compared to|

||||tumor NGS (TP53 [62 v 72%], ARID1A [12 v 20%] , CDKN2A [10 v 16%], APC [10 v 13%] , ATM [10 v|tumor NGS (TP53 [62 v 72%], ARID1A [12 v 20%] , CDKN2A [10 v 16%], APC [10 v 13%] , ATM [10 v|tumor NGS (TP53 [62 v 72%], ARID1A [12 v 20%] , CDKN2A [10 v 16%], APC [10 v 13%] , ATM [10 v|tumor NGS (TP53 [62 v 72%], ARID1A [12 v 20%] , CDKN2A [10 v 16%], APC [10 v 13%] , ATM [10 v|tumor NGS (TP53 [62 v 72%], ARID1A [12 v 20%] , CDKN2A [10 v 16%], APC [10 v 13%] , ATM [10 v|tumor NGS (TP53 [62 v 72%], ARID1A [12 v 20%] , CDKN2A [10 v 16%], APC [10 v 13%] , ATM [10 v|tumor NGS (TP53 [62 v 72%], ARID1A [12 v 20%] , CDKN2A [10 v 16%], APC [10 v 13%] , ATM [10 v|

||||12%], PIK3CA [7 v 12%] ), although cfDNA was detected more frequently in patients with|12%], PIK3CA [7 v 12%] ), although cfDNA was detected more frequently in patients with|12%], PIK3CA [7 v 12%] ), although cfDNA was detected more frequently in patients with|12%], PIK3CA [7 v 12%] ), although cfDNA was detected more frequently in patients with|12%], PIK3CA [7 v 12%] ), although cfDNA was detected more frequently in patients with|12%], PIK3CA [7 v 12%] ), although cfDNA was detected more frequently in patients with|12%], PIK3CA [7 v 12%] ), although cfDNA was detected more frequently in patients with|

||||metastatic disease compared to localized disease (p=0.02). cfDNA did not detect copy number|metastatic disease compared to localized disease (p=0.02). cfDNA did not detect copy number|metastatic disease compared to localized disease (p=0.02). cfDNA did not detect copy number|metastatic disease compared to localized disease (p=0.02). cfDNA did not detect copy number|metastatic disease compared to localized disease (p=0.02). cfDNA did not detect copy number|metastatic disease compared to localized disease (p=0.02). cfDNA did not detect copy number|metastatic disease compared to localized disease (p=0.02). cfDNA did not detect copy number|

||||alterations as frequently as patient-matched tumor NGS (41 v 16%, p,0.01), including ERB-|alterations as frequently as patient-matched tumor NGS (41 v 16%, p,0.01), including ERB-|alterations as frequently as patient-matched tumor NGS (41 v 16%, p,0.01), including ERB-|alterations as frequently as patient-matched tumor NGS (41 v 16%, p,0.01), including ERB-|alterations as frequently as patient-matched tumor NGS (41 v 16%, p,0.01), including ERB-|alterations as frequently as patient-matched tumor NGS (41 v 16%, p,0.01), including ERB-|alterations as frequently as patient-matched tumor NGS (41 v 16%, p,0.01), including ERB-|

||||detectable ERBB2amp on cfDNA compared to HER2 IHC 2+ tumors (50 v 9% p=0.03). Addi-|detectable ERBB2amp on cfDNA compared to HER2 IHC 2+ tumors (50 v 9% p=0.03). Addi-|detectable ERBB2amp on cfDNA compared to HER2 IHC 2+ tumors (50 v 9% p=0.03). Addi-|detectable ERBB2amp on cfDNA compared to HER2 IHC 2+ tumors (50 v 9% p=0.03). Addi-|detectable ERBB2amp on cfDNA compared to HER2 IHC 2+ tumors (50 v 9% p=0.03). Addi-|detectable ERBB2amp on cfDNA compared to HER2 IHC 2+ tumors (50 v 9% p=0.03). Addi-|detectable ERBB2amp on cfDNA compared to HER2 IHC 2+ tumors (50 v 9% p=0.03). Addi-|

||||tionally, those with detectable ERBB2amp on cfDNA had a higher copy number on tumor NGS|tionally, those with detectable ERBB2amp on cfDNA had a higher copy number on tumor NGS|tionally, those with detectable ERBB2amp on cfDNA had a higher copy number on tumor NGS|tionally, those with detectable ERBB2amp on cfDNA had a higher copy number on tumor NGS|tionally, those with detectable ERBB2amp on cfDNA had a higher copy number on tumor NGS|tionally, those with detectable ERBB2amp on cfDNA had a higher copy number on tumor NGS|tionally, those with detectable ERBB2amp on cfDNA had a higher copy number on tumor NGS|

||||compared to those with undetectable cfDNA (median 39 [IQR 23-46] v 10 [IQR 6-15] p,0.01).|compared to those with undetectable cfDNA (median 39 [IQR 23-46] v 10 [IQR 6-15] p,0.01).|compared to those with undetectable cfDNA (median 39 [IQR 23-46] v 10 [IQR 6-15] p,0.01).|compared to those with undetectable cfDNA (median 39 [IQR 23-46] v 10 [IQR 6-15] p,0.01).|compared to those with undetectable cfDNA (median 39 [IQR 23-46] v 10 [IQR 6-15] p,0.01).|compared to those with undetectable cfDNA (median 39 [IQR 23-46] v 10 [IQR 6-15] p,0.01).|compared to those with undetectable cfDNA (median 39 [IQR 23-46] v 10 [IQR 6-15] p,0.01).|

||||Baseline detection of ctDNA may indicate a poor prognosis; among patients with locally ad-|Baseline detection of ctDNA may indicate a poor prognosis; among patients with locally ad-|Baseline detection of ctDNA may indicate a poor prognosis; among patients with locally ad-|Baseline detection of ctDNA may indicate a poor prognosis; among patients with locally ad-|Baseline detection of ctDNA may indicate a poor prognosis; among patients with locally ad-|Baseline detection of ctDNA may indicate a poor prognosis; among patients with locally ad-|Baseline detection of ctDNA may indicate a poor prognosis; among patients with locally ad-|

||||vanced disease (median follow up 20.1 months), 0 of 10 with undetectable ctDNA died compared|vanced disease (median follow up 20.1 months), 0 of 10 with undetectable ctDNA died compared|vanced disease (median follow up 20.1 months), 0 of 10 with undetectable ctDNA died compared|vanced disease (median follow up 20.1 months), 0 of 10 with undetectable ctDNA died compared|vanced disease (median follow up 20.1 months), 0 of 10 with undetectable ctDNA died compared|vanced disease (median follow up 20.1 months), 0 of 10 with undetectable ctDNA died compared|vanced disease (median follow up 20.1 months), 0 of 10 with undetectable ctDNA died compared|

||||to 5 (26%) of 19 with detectable ctDNA (p=0.08). Among patients with untreated, metastatic|to 5 (26%) of 19 with detectable ctDNA (p=0.08). Among patients with untreated, metastatic|to 5 (26%) of 19 with detectable ctDNA (p=0.08). Among patients with untreated, metastatic|to 5 (26%) of 19 with detectable ctDNA (p=0.08). Among patients with untreated, metastatic|to 5 (26%) of 19 with detectable ctDNA (p=0.08). Among patients with untreated, metastatic|to 5 (26%) of 19 with detectable ctDNA (p=0.08). Among patients with untreated, metastatic|to 5 (26%) of 19 with detectable ctDNA (p=0.08). Among patients with untreated, metastatic|

||||disease (median follow up 24.3 months), patients with undetectable ctDNA had a non-|disease (median follow up 24.3 months), patients with undetectable ctDNA had a non-|disease (median follow up 24.3 months), patients with undetectable ctDNA had a non-|disease (median follow up 24.3 months), patients with undetectable ctDNA had a non-|disease (median follow up 24.3 months), patients with undetectable ctDNA had a non-|disease (median follow up 24.3 months), patients with undetectable ctDNA had a non-|disease (median follow up 24.3 months), patients with undetectable ctDNA had a non-|

||||significant, improvement in PFS (HR 0.28 95% CI 0.08-1.17; p=0.08) and OS (HR 0.45 95%|significant, improvement in PFS (HR 0.28 95% CI 0.08-1.17; p=0.08) and OS (HR 0.45 95%|significant, improvement in PFS (HR 0.28 95% CI 0.08-1.17; p=0.08) and OS (HR 0.45 95%|significant, improvement in PFS (HR 0.28 95% CI 0.08-1.17; p=0.08) and OS (HR 0.45 95%|significant, improvement in PFS (HR 0.28 95% CI 0.08-1.17; p=0.08) and OS (HR 0.45 95%|significant, improvement in PFS (HR 0.28 95% CI 0.08-1.17; p=0.08) and OS (HR 0.45 95%|significant, improvement in PFS (HR 0.28 95% CI 0.08-1.17; p=0.08) and OS (HR 0.45 95%|

||||CI 0.10-1.96; p=0.20) compared to patients with detectable ctDNA, independent of disease|CI 0.10-1.96; p=0.20) compared to patients with detectable ctDNA, independent of disease|CI 0.10-1.96; p=0.20) compared to patients with detectable ctDNA, independent of disease|CI 0.10-1.96; p=0.20) compared to patients with detectable ctDNA, independent of disease|CI 0.10-1.96; p=0.20) compared to patients with detectable ctDNA, independent of disease|CI 0.10-1.96; p=0.20) compared to patients with detectable ctDNA, independent of disease|CI 0.10-1.96; p=0.20) compared to patients with detectable ctDNA, independent of disease|

||||complimentary tool for molecular characterization and potential prognostication in patients with|complimentary tool for molecular characterization and potential prognostication in patients with|complimentary tool for molecular characterization and potential prognostication in patients with|complimentary tool for molecular characterization and potential prognostication in patients with|complimentary tool for molecular characterization and potential prognostication in patients with|complimentary tool for molecular characterization and potential prognostication in patients with|complimentary tool for molecular characterization and potential prognostication in patients with|

||||EG cancer. Research Sponsor: None.|||||||

||||||Alterations|ERBB2 amplification|Recurrence/Progression|||

||||||Detected|||Free Survival|Overall Survival|

||||Cohort|# Patients|on cfDNA|All Patients|HER2+|(Undetectable v Detectable)|(Undetectable v Detectable)|

||Population|Prevalence (%) (Range)|Total Locally|98 (100%) 29 (29%)|79 (81%) 19 (66%)|10% 0%|34% 0%|-HR 0.93|-HR not calculable; no deaths|

|HER2-low HER2+|GC GEC GC GEC|26.9 (4.9-71.6) 26.9 (5.7-57.8) 13.1 (6.4-32.3) 16.5 (4.8-60.8)|advanced Metastatic Progressive|48 (48%) 21 (21%)|40 (83%) 20 (95%)|10% 24%|63% 36%|(95% CI 0.23-3.75 p=0.92) HR 0.28 (95% CI 0.08-1.17 p=0.08) -|among patients with undetectable ctDNA (p=0.08) HR 0.45 (95% CI 0.10-1.96 p=0.20) -|

||||disease|||||||

|1.18-2.42, p=0.004) and RFS (HR 1.42, 95%CI 1.02-1.98, p=0.038), while WBCmax and infectious complications were not. Regarding the pattern of recurrence, hematogenous recurrence was significantly more frequent in the high-CRPmax group (16.7%) than in the low-CRPmax group (3.8%, p,0.001). 412 reviewed data on 535 cases with ESCC enrolled in C-CAT between June 2019 and Poster Session Methods: We retrospectively December 2022. The clinical features, genomic variants classified as oncogenic/ pathogenic, MSI/TMB status and response to treatment (response rate; RR and time to treatment failure; TTF) were evaluated. Results: Oncogenic/pathogenic variants were detected in 527 cases (98%), and the Top 5 gene mutations were TP53 (94.6%), CDKN2A (56.6%), CDKN2B (43.7%), CCND1 (42.6%), and FGF19 (38.9%), in order of prevalence. No patient had MSI-H, and number of patients with TMB-H ($10 Muts/Mb) and HRD were 82 (15%) and 15 (13%), respectively. Regarding the efficacy of first-line chemotherapy (IO-containing regimen in 5 cases, 0.9 %), the TTF was significantly shorter in TMB-H cases than in TMB-L cases (11.8 vs 17.5 weeks, p=0.006). No difference in response to anti-PD-1 antibody was observed depending on TMB status (RR, TMB-L 19 % vs. TMB-H 12 %). Patients with BRCA1/2 mutations tended to respond better to first-line chemotherapy including platinum drugs, although there was no difference in response to treatment with or without other HRR mutations. The percentages of cases delivered new treatments based on CGP testing was 6.8%. The percentage of cases with HRD or TMB-H suggested|| |---|---|

||new treatment based on GCP testing was significantly higher than those without them.|

||Conclusions: Patients with BRCA1/2 mutations are more sensitive to platinum com-|

||bination chemotherapy and may be good candidates for PARP inhibitors in ESCC. Since|

||TMB-H patients are resistant to standard chemotherapies, we should promote the|

||development of immunotherapy and molecular-based targeted therapies for this|

||population. Research Sponsor: None.|

|413|Poster Session|

|[95%CI] and any difference assessed by the log-rank test. Results: From January 2019 until December 2022, 122 LAGC patients were treated with perioperative FLOT. Median age was 56 years, 53.2% were female and 84.4% were ECOG 0. Primary prophylaxis (PP) was used by 58 patients (47.5%); there was no difference between clinical and tumor features between both groups regarding age, sex, ECOG, T and N staging and Lauren's subtype. PP costs raised treatment costs up to 15%. Grade 3 or 4 neutropenia occurred more frequently among patients without PP (65.6 vs. 1.7%; p , 0.001). There was no difference in the frequency of FN between groups (7.8 vs. 0%; p = 0.06). Overall patients, pCR occurred in 11.8% os patients. Regarding the influence of PP in pathological response after FLOT chemo-therapy, there was no difference between PP vs non-PP patients with pCR (14.3% vs 9.5%, p = 0.57). Median follow-up was 27.4 (range 2.8 -70.6 months). Twenty-six patients (21.Prospective assessment of adenocarcinoma of esophagogastric junction (AEG) following radical resection: Real-world insights from the CLAEG study. First Author: Jiabin Zheng, Guangdong Provincial People's Hospital (Guang-dong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China Background:| |---|

|infusion on days 1, 8, 15. A Simon's two-stage optimal design is applied (table below). The|||||

|primary endpoint is 60-day OC rate. Secondary endpoints are 30-day OC rate, time to OC, OC|||||

|duration, safety, overall survival and quality of life. Till July 2023, a total of 34 pts has been|||||

|enrolled (16 in cohort A, 9 in cohort B, 9 in cohort C). Inclusion Criteria: 18-75 years old; Eastern|||||

|Cooperative Oncology Group performance status # 3; adenocarcinoma of stomach or gas-|||||

|troesophageal junction; peritoneal carcinomatosis established by imaging data or pathological|||||

|evidence; MBO below the Treitz ligament based on clinical grounds or radiological findings;|||||

|inappropriate for operation judged independently by two surgeons; written informed consent.|||||

|Cohort B (second-line)|20%|45%|10|12|

||||Disitamab vedotin is|

|||an antibody-drug conjugate comprising a novel HER2-directed monoclonal antibody, In|an antibody-drug conjugate comprising a novel HER2-directed monoclonal antibody, In|

|||previous study C008, RC48 showed a good safety profile and promising activity towards|previous study C008, RC48 showed a good safety profile and promising activity towards|

|||GC, and showed equivalent efficacy for HER2 IHC 2+ or HER2 IHC 3+ tumors.|GC, and showed equivalent efficacy for HER2 IHC 2+ or HER2 IHC 3+ tumors.|

|||Methods: This study is a single-arm, phase II trial carry out at 16 academic hospitals in|Methods: This study is a single-arm, phase II trial carry out at 16 academic hospitals in|

|||China, and will evaluate DV combined with Sintilimab and S-1 in patients with HER2-|China, and will evaluate DV combined with Sintilimab and S-1 in patients with HER2-|

|||expressing unresectable gastric cancer. Eligible patients are at $ 18 to # 75 years old;|expressing unresectable gastric cancer. Eligible patients are at $ 18 to # 75 years old;|

|||histologically confirmed, unresectable stage IV GC or GEJA; Single initial unresectable|histologically confirmed, unresectable stage IV GC or GEJA; Single initial unresectable|

|||factor. For example, peritoneal metastasis (P1), Intraperitoneal free cancer cells positive|factor. For example, peritoneal metastasis (P1), Intraperitoneal free cancer cells positive|

|||(CY1), Paraaortic lymph node metastasis, liver metastasis (# 3 lesions, and # 5 cm for a|(CY1), Paraaortic lymph node metastasis, liver metastasis (# 3 lesions, and # 5 cm for a|

|||single lesion), ovarian metastasis; and documented histologically confirmed HER2 IHC|single lesion), ovarian metastasis; and documented histologically confirmed HER2 IHC|

|||3+ or 2+; ECOG 0-1; at least one unresectable, measurable tumor lesion according to the|3+ or 2+; ECOG 0-1; at least one unresectable, measurable tumor lesion according to the|

|||RECIST version 1.1; adaptable function of the heart, liver, and kidney. 30 patients will be|RECIST version 1.1; adaptable function of the heart, liver, and kidney. 30 patients will be|

|||enrolled in this trial and receive Disitamab Vedotin(2.5mg/kg, IV, Q3W), Sintilimab|enrolled in this trial and receive Disitamab Vedotin(2.5mg/kg, IV, Q3W), Sintilimab|

|||(200 mg, IV, Q3W) and S-1 (twice daily on D1-14 are given at a dose calculate according|(200 mg, IV, Q3W) and S-1 (twice daily on D1-14 are given at a dose calculate according|

|||to the body surface area and repeated every 3 weeks), until patients assessed by MDT to|to the body surface area and repeated every 3 weeks), until patients assessed by MDT to|

|||meet the criteria for surgical resection undergo gastrectomy. And the patients with|meet the criteria for surgical resection undergo gastrectomy. And the patients with|

|||peritoneal dissemination will combine with intraperitoneal administration of paclitaxel|peritoneal dissemination will combine with intraperitoneal administration of paclitaxel|

|||(60mg / m2, Q3W). The primary endpoint is R0 resection rate, Secondary endpoints|(60mg / m2, Q3W). The primary endpoint is R0 resection rate, Secondary endpoints|

|||include cORR, OS, RFS and safety. Seven patients have been enrolled in this study.|include cORR, OS, RFS and safety. Seven patients have been enrolled in this study.|

|||Clinical trial information: NCT05627414. Research Sponsor: None.|Clinical trial information: NCT05627414. Research Sponsor: None.|

|TPS429|Trials in Progress Poster Session|TPS430|Trials in Progress Poster Session|

|with most samples from White cancer patients. Results: A total of 872 GC (mean age at|with most samples from White cancer patients. Results: A total of 872 GC (mean age at|

|registration [SD]: 64y [12] ; percent males: 65%), 265 EC (64y [9]; 78%) and 495 PC (64y|registration [SD]: 64y [12] ; percent males: 65%), 265 EC (64y [9]; 78%) and 495 PC (64y|

|2 in|||

|primary tumor and metastatic nodules in peritoneum of GC using immunohistochemical|||

|(IHC) staining. Methods: In 42 patients diagnosed with stage IV GC with PM at our|||

|Department from 2014 to 2022, biopsy samples of primary tumor and peritoneal nodules|||

|were obtained and the expression of CLDN18.2 in tumor cells by IHC staining using|||

|specific antibody for CLDN18.2 (clone: 43-14A, prediluted; Ventana) followed by the|||

|incubation with secondary antibody and the primary antibody binding visualized using|||

|the DAB IHC Detection Kit. The intensity of the membrane and cytosolic staining was|||

|classified as 0 (no reactivity), 1+ (weak), 2+ (moderate), and 3+ (strong). Samples were|||

|defined as CLDN18.2-positive when tumor cells showed specific staining with at least 1+|||

|intensity in tumor cells. Percentage of overall CLDN18.2 positive cells was determined|||

|by the estimated number of CLDN18.2+ cells divided by the estimated overall number of|||

|tumor cells in any fractions. Her2 expression was also examined in parallel.|||

|Results: The histology type of primary tumor was differentiated in 7, undifferentiated in|||

|33, and unknown in 2 patients. CLDN18.2-positivity was detected in 31 (74%) of primary|||

|tumors, including 5 (71%) differentiated and 26(79%) undifferentiated tumors. CLDN18.2|||

|was positively detected in 15 (35%) disseminated nodules, in 4 (57%) differentiated and|||

|11 (33%) in undifferentiated cases, respectively. All these cases also showed CLDN18.2-|||

|positve in primary sites. However, expression of CLDN18.2 in PM was not detected in 16|||

|(52%) cases which showed CLDN18.2-positive for primary tumor. Moderate-to-strong|||

|CLDN18.2 expression ($2+ membrane staining intensity in $40% of tumor cells) was|||

|observed in 13 (31%) of primary tumor, but only in 2 (5%) of PM. HER2 was positive in 5|||

||||B2amp (22 v 10%, p=0.05), though patients with HER2 IHC 3+ tumors were more likely to have|B2amp (22 v 10%, p=0.05), though patients with HER2 IHC 3+ tumors were more likely to have|B2amp (22 v 10%, p=0.05), though patients with HER2 IHC 3+ tumors were more likely to have|B2amp (22 v 10%, p=0.05), though patients with HER2 IHC 3+ tumors were more likely to have|B2amp (22 v 10%, p=0.05), though patients with HER2 IHC 3+ tumors were more likely to have|B2amp (22 v 10%, p=0.05), though patients with HER2 IHC 3+ tumors were more likely to have|B2amp (22 v 10%, p=0.05), though patients with HER2 IHC 3+ tumors were more likely to have|

||||burden. Conclusions: Our findings highlight the utility of cfDNA with MSK ACCESS as a|burden. Conclusions: Our findings highlight the utility of cfDNA with MSK ACCESS as a|burden. Conclusions: Our findings highlight the utility of cfDNA with MSK ACCESS as a|burden. Conclusions: Our findings highlight the utility of cfDNA with MSK ACCESS as a|burden. Conclusions: Our findings highlight the utility of cfDNA with MSK ACCESS as a|burden. Conclusions: Our findings highlight the utility of cfDNA with MSK ACCESS as a|burden. Conclusions: Our findings highlight the utility of cfDNA with MSK ACCESS as a|

|Socioeconomic status|0.17|0.17|

||445|Poster Session| |---|---|---|

|Background: Methods: This retrospective, multisite cohort study included pts with a diagnosis of unresectable locally advanced or met-|San Antonio, San Antonio, TX Background: cirrhosis. We aim to supplement the trial data with real world outcomes of individuals||

|astatic CCA who were initially prescribed pemigatinib on or after 04/17/2020. Eligible pts|with unresectable HCC treated with (A+B) in the first line setting including patients with|with unresectable HCC treated with (A+B) in the first line setting including patients with|

|were $18 years at pemigatinib prescription and had $4 months (mo) of follow-up|advanced cirrhosis. Methods: This was a single-center, retrospective analysis of pa-|advanced cirrhosis. Methods: This was a single-center, retrospective analysis of pa-|

|(unless ,4 mo due to death). Pts who received pemigatinib as part of a clinical trial or|tients with advanced HCC treated with A+B as first line systemic therapy between May|tients with advanced HCC treated with A+B as first line systemic therapy between May|

|those who received systemic therapy for another primary malignancy (other than cancer|2020-January 2023. Patient characteristics, HCC stage, treatment information, adverse|2020-January 2023. Patient characteristics, HCC stage, treatment information, adverse|

|of unknown primary or hepatic cancer) were ineligible. Participating physicians from|events and survival data were collected. Outcomes evaluated included progression free|events and survival data were collected. Outcomes evaluated included progression free|

|Cardinal Health's Oncology Provider Extended Network-approximately 72% from|survival (PFS), overall survival (OS), overall response rate (ORR) using RECIST 1.1 and|survival (PFS), overall survival (OS), overall response rate (ORR) using RECIST 1.1 and|

|community oncology practices-abstracted data from the medical records of eligible|adverse events (AE) rate according to CTCAE v5. R v4.2.1 was used for analysis.|adverse events (AE) rate according to CTCAE v5. R v4.2.1 was used for analysis.|

|patients into electronic case report forms. Results were summarized using descriptive|Results: We identified a total of 41 patients with advanced stage HCC who received A+B|Results: We identified a total of 41 patients with advanced stage HCC who received A+B|

|statistics. Results: Data from 120 pts (49% male; 55% White; 19% Hispanic; median age|as first line systemic therapy. The median age at diagnosis was 69 years (range 42 -85).|as first line systemic therapy. The median age at diagnosis was 69 years (range 42 -85).|

|at pemigatinib prescription, 65 years) were collected from 18 physicians/practices.|34(83%) of the patients were males. 8(20%) of the patients were African American.|34(83%) of the patients were males. 8(20%) of the patients were African American.|

|Testing for FGFR2 alterations was completed in 93% (n=111) of pts; of those, all but one|7(17%) patients had CP B cirrhosis. Median PFS on A+B among all patients was|7(17%) patients had CP B cirrhosis. Median PFS on A+B among all patients was|

|patient (result unknown) tested positive, and 95% were tested using next-generation|10.82 months (95% CI: 5.38 -16.26). Median OS from time of A+B initiation was|10.82 months (95% CI: 5.38 -16.26). Median OS from time of A+B initiation was|

|sequencing. At time of pemi prescription, 90% of pts had metastatic disease. Across all|14.01 months (95% CI: 10.67 -17.34). Median OS and PFS were significantly shorter|14.01 months (95% CI: 10.67 -17.34). Median OS and PFS were significantly shorter|

|pts, 94% and 6% were prescribed pemigatinib as 2nd and 3rd line of therapy, re-|among CP B patients, 6.84(95% CI: NE -19.36, p = 0.003) and 6.8(95% CI: NE -19.33, p =|among CP B patients, 6.84(95% CI: NE -19.36, p = 0.003) and 6.8(95% CI: NE -19.33, p =|

|spectively. The most common starting dosage was 13.5 mg daily for 14 days of 21-day|0.016) respectively. Hazard ratio (HR) for death from any cause among CP B patients|0.016) respectively. Hazard ratio (HR) for death from any cause among CP B patients|

|cycle (87.5% of pts). Among the 60 pts who discontinued pemi during the 6.5-month|was 4.87(95% CI: 1.35 -17.48, p ,0.01) compared to others. ORR was 31.42%. 10/|was 4.87(95% CI: 1.35 -17.48, p ,0.01) compared to others. ORR was 31.42%. 10/|

|median study follow-up period, 68% discontinued due to disease progression. Median|23(39.13%) patients with CP A had overall response, while 1/7(14.28%) patients with CP|23(39.13%) patients with CP A had overall response, while 1/7(14.28%) patients with CP|

|RW progression-free survival (rwPFS) from date of pemigatinib initiation was 7.4 (95%|B had overall response. AE of any grade was observed in 30(73.2%) patients.10(24.4%)|B had overall response. AE of any grade was observed in 30(73.2%) patients.10(24.4%)|

|CI: 6.4-8.6) mo. Among the 116 patients with tumor response data available, RW overall|patients had grade 3 or more events, 2(28.5%) among CP B patients. 1(14.2%) had GI|patients had grade 3 or more events, 2(28.5%) among CP B patients. 1(14.2%) had GI|

|response rate (rwORR) was 61% (95% CI: 52% -71%). Conclusions: This study com-|bleed among CP B patients, while 4(9.7) patients had GI bleed overall. Common adverse|bleed among CP B patients, while 4(9.7) patients had GI bleed overall. Common adverse|

|plements the FIGHT-202 clinical trial by assessing the use of pemigatinib among a|events included fatigue (26.8%), anorexia (26.8%), aspartate aminotransferase (AST)|events included fatigue (26.8%), anorexia (26.8%), aspartate aminotransferase (AST)|

|443 elevation (14.6%), proteinuria (17%), rash (21.9%). Conclusions: 446 diverse population of patients with CCA under RW conditions. Secondarily, the rwORR and rwPFS from this study support the clinical benefit of pemigatinib demonstrated in FIGHT-202. Research Sponsor: Incyte Corporation. Poster Session|Poster Session||

|Comparing first-line (1L) atezolizumab plus bevacizumab (A+B) to lenva-|||

|tinib (L) or sorafenib (S) in patients with unresectable hepatocellular car-|||

|cinoma (uHCC): Findings from the National Veteran Health Administration|||

|(VHA) database. First Author: David Edward Kaplan, Division of Gastroenterology and|||

|Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA|||

|||MEDLINE)|

||were conducted for epidemiology (Jan 01 2017-Feb 06 2023) and treatment guidelines/|were conducted for epidemiology (Jan 01 2017-Feb 06 2023) and treatment guidelines/|

||patterns (Jan 01 2012-Feb 06 2023). Conference abstracts were also searched|patterns (Jan 01 2012-Feb 06 2023). Conference abstracts were also searched|

|aetiology, Child-Pugh 453 received L, and|(2019-2022). Eligibility criteria included global studies (English language) in adults with|(2019-2022). Eligibility criteria included global studies (English language) in adults with|

|class (CP-C), ECOG-PS, BCLC stage, alpha-fetoprotein (AFP) levels, treatment line, portal vein tumor thrombosis (PVTT), and extrahepatic spread (EHS). Restricted mean survival time (RMST) difference analyses stratified by HIV status were performed for OS and PFS at 3, 6 and 9 months. Results: We accrued 46 PWH and 400 HIV-, treated mostly in the first-line setting 1,016 received S. Compared with patients receiving L or S, those treated with A+B had a higher proportion of CP A5 (47% and 35% vs. 54%, respectively; both p,0.05), a similar proportion of A6 (30% and 32% vs. 31%, p=0.683 and 0.681, respectively), a lower proportion of B7 (15% and 20% vs. 9%, respectively; both p,0.05), and a greater comorbidity burden as measured by the mean Charlson Comorbidity Index (CCI) (5.8 [L or S] vs 6.6 [A+B] , both p,0.05). Median OS (mOS) was 12.8 months (95% CI: 10.6, 17.1) in the A+B cohort, compared (58.7% vs. 43.7%) with either atezolizumab plus bevacizumab (28.3% vs 17.5%) or anti-PD-1 to 9.5 months [95% CI: 7.8, 11.4] in the L cohort, and 8.0 months [95% CI: 7.1, 8.6] in the S cohort. In subgroup monotherapy. Median age at ICI start was 62 (38-76) and 64 (18-87); viral hepatitis (HCV: analyses, longer mOS was observed with A+B than with L or S in CP A patients and those with ALBI grades 1-58.7%; HBV: 34.8%) were the prevalent aetiologies in PWH, non-viral (46%) was the most common in HIV-; most patients had BCLC-C HCC (84.8% and 82.3%). In PWH, median CD4 count was 345 cells/mm 3 (IQR: 200-465); viral load was undetectable in 45 patients, all were established on combined anti-retroviral therapy. Following PSM, 44 PWH and 117 HIV-were included. Median OS was 7.5 months (95%CI: 5.2-NR) in PWH and 10.8 months (95%CI: 7.3-2A; similar mOS was observed among those with more severe liver dysfunction (Table). In multivariable analysis, A + B was associated with a 26% lower risk of death relative to L (HR=0.74, 95% CI: 0.62-0.88) and 30% lower risk of death compared to S (HR = 0.70, 95%CI 0.60-0.82), both p,0.001. Conclusions: In a real-world VHA experience with A+B among diverse patient groups, a clinically notable survival benefit was observed with A+B compared to L or S. Future evaluations of the safety of using A+B in patients with greater liver dysfunction, including CP B and cirrhosis, are needed to evaluate the expanded use of A+B. Research 19.5) in HIV-(HR: 0.89; 95%CI: 0.56-1.42; p=0.58). Presence of PVTT, AFP.400 ng/mL, and Sponsor: F. Hoffman La Roche. ECOG-PS=1 but not HIV status were associated with worse OS in uni-and multivariable models. Median PFS was 2.8 months (95%CI: 2.6-4.8) for PWH vs 3.0 months (95%CI: 2.4-5.3) for HIV-(HR: 0.83-95%CI:0.56-1.24 ;p=0.38); HIV status was not associated with worse PFS. RMST confirmed no OS or PFS differences based on HIV status. In matched cohorts, neither ORR (21% vs. 19.1%, p=0.97) nor DCR (44.7% vs. 55.4%, p=0.19) were associated with HIV A+B L S Median Follow-up, Months 8.5 8.2 7.6 mOS(months) [95% CI] CP A (n=1,374) n = 345|metastatic and/or unresectable BTC. Results: Overall, 264 studies were included (epide-miology=170, treatment guidelines=14, treatment patterns=50, HRQoL=12, economic burden=18). In the US, Europe and Asia, age-standardized incidence rates were 5.04, 8.39-8.78 and 9.1-10.1 (per 100,000 person-years) and prevalence rates were 0.01%, 0.02-0.34% and 0.02-2.61%, respectively. Treatment pattern studies were mainly from Asia, Europe (n=19 each) and North America (n=10). Gemcitabine [gem] -based chemo-therapy was most common in 1L BTC (24-100%) and fluorouracil-based regimens were common in 2L+ BTC (12.3-74.3%). Median overall survival (mOS) for gem-based and fluorouracil-based 1L regimens were 7.7-14.8 months and 7-16.7 months, respectively. Disease progression/toxicity frequently led to treatment discontinuation/dose modifica-tions. In the US, use of non-guideline-based regimens increased by line of therapy (LOT). Among the clinical studies (n=5) reporting HRQoL in 1L, n=4 assessed gem-based com-binations. BTC impaired HRQoL domains for anxiety, tiredness (EORTC QLQ-BIL21), work productivity, activity impairment (WPAI scale) and depression (PHQ-9). BTC was associated with substantial economic burden. Mean total all-cause healthcare costs per patient per month (PPPM) increased by LOT (US; 1L: $19,589-25,517, 2L: $22,617-29,721, 3L:|metastatic and/or unresectable BTC. Results: Overall, 264 studies were included (epide-miology=170, treatment guidelines=14, treatment patterns=50, HRQoL=12, economic burden=18). In the US, Europe and Asia, age-standardized incidence rates were 5.04, 8.39-8.78 and 9.1-10.1 (per 100,000 person-years) and prevalence rates were 0.01%, 0.02-0.34% and 0.02-2.61%, respectively. Treatment pattern studies were mainly from Asia, Europe (n=19 each) and North America (n=10). Gemcitabine [gem] -based chemo-therapy was most common in 1L BTC (24-100%) and fluorouracil-based regimens were common in 2L+ BTC (12.3-74.3%). Median overall survival (mOS) for gem-based and fluorouracil-based 1L regimens were 7.7-14.8 months and 7-16.7 months, respectively. Disease progression/toxicity frequently led to treatment discontinuation/dose modifica-tions. In the US, use of non-guideline-based regimens increased by line of therapy (LOT). Among the clinical studies (n=5) reporting HRQoL in 1L, n=4 assessed gem-based com-binations. BTC impaired HRQoL domains for anxiety, tiredness (EORTC QLQ-BIL21), work productivity, activity impairment (WPAI scale) and depression (PHQ-9). BTC was associated with substantial economic burden. Mean total all-cause healthcare costs per patient per month (PPPM) increased by LOT (US; 1L: $19,589-25,517, 2L: $22,617-29,721, 3L:|

|||||||||||449|Poster Session|||| |---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|

|||||||||||Results: A total of 1115 pts (median [range] age: 63 [18.0-97.0] yrs) were assessed; 83.2% (928/1115) were|||||

|||||||||||males, 49.1% (422/859) were current or ex-smokers, 21.4% (122/571) consumed alcohol. Most common|||||

|||||||||||etiologies were hepatitis B (48.9% [529/1082]), hepatitis C (23.1% [250/1082] ) and alcoholic liver disease (6.6%|||||

|||||||||||[72/1082]). At index date, 22.3% (249/1115) and 77.7% (866/1115) presented with BCLC stage B and C,|||||

|||||||||||respectively with main portal vein invasion in 23.5% (262/1114), .50% liver involvement in 23.1% (250/1081)|||||

|||||||||||and extrahepatic metastases in 48.5% (541/1115). After index date, treatment modalities included systemic|||||

|||||||||||therapy (88.2% [992/1112] (including sorafenib [77.5%] , nivolumab [21.3%], lenvatinib [19.8%] , regorafenib|||||

|||||||||||[15.6%]), transarterial chemoembolization (TACE) (20.8% [232/1115] ), and surgery (2.6% [29/1115]). The mPFS|||||

|||||||||||was 6.6 (95% CI 6.0, 7.2) months and mOS was 13.1 (95% CI 11.6, 14.2) months. Conclusions: Survival outcomes.|||||

|||||||||||mPFS (months)|mOS (months)|OS rates (%) (95% CI)|||

|||||||||||Variables|(95% CI)|(95% CI)|12-month 24-month||

|||||||||||Overall (N=1115)|6.2|13.1|52.2|30.7|

|||||White|||AA|Hispanic|BCLC B (N=249)|(5.5, 6.7) 8.9|(11.6, 14.2) 18.6|(49.1, 55.2) 66.2|(27.9, 33.5) 39.1||

|mOS [95% CI], in months A+B S L HR [95% CI]|n=376 13.3 [10.9, 17.4] n=943 7.9 [7.0, 8.5] n=419 9.0 [7.6, 11.3]|n=232 11.1 [9.1,13.6] n=634 7.6 [6.7,8.7] n=274 8.7 [7.2,11.2]|n=109 19.5 [12.1, NR] n=217 8.2 [6.7,10.8] n=111 11.5 [7.0, 14.4]|n=35 17.5 [9.2,NR] n=92 7.9 [5.7,9.1] n=34 8.1 [4.0,14.4]|BCLC C (N=866) TKIs (N=889) Immune Checkpoint Inhibitors (N=325) VEGF-mAb/VEGFR2 mAb (N=22)|(6.9, 11.0) 5.5 (4.8, 6.1) 5.4 (4.8, 6.0) 6.1 (4.0, 8.1) -|(16.3, 22.2) 11.1 (9.8, 12.7) 13.2 (12.0, 14.5) 19.4 (15.8, 22.2) 27.0|(59.8, 72.0) 48.1 (44.7, 51.5) 53.3 (49.9, 56.6) 64.5 (59.0, 69.7) 81.5|(32.7, 45.5) 28.2 (25.1, 31.4) 30.9 (27.8, 34.1) 41.1 (35.7, 46.7) 59.2||||||

|A+B vs S A+B vs L||0.69 [0.59, 0.81]* 0.73 [0.60, 0.89]* 0.65 [0.47, 0.90] * 0.55 [0.31, 0.95]* 0.74 [0.62, 0.89] * 0.77 [0.61, 0.96]* 0.70 [0.49, 1.00] 0.67 [0.36, 1.27]|Combination therapy (N=21)|8.5|(21.2, 33.8) 20.6|(61.9, 93.7) 66.7|(38.8, 77.6) 38.1||||||||

|* p , 0.05.||||||||||(3.4, NA)|(10.5, 26.1)|(43.0, 85.4)|(18.1, 61.6)||

|450|||||||Poster Session||||||||

|Zanidatamab (zani) in previously treated HER2+ biliary tract cancer (BTC):|||||||||||||||

|Impact on patient-reported pain outcomes in the phase 2b HERIZON-BTC-|||||||||||||||

|01 study. First Author: Shubham Pant, The University of Texas MD Anderson Cancer|||||||||||||||

|Center, Houston, TX|||||||||||||||

||||||||01 (NCT04466891), an||||||||

|ongoing, open-label, Phase 2b study, is assessing zani (20 mg/kg IV Q2W) in patients with HER2+|||||||||||||||

|(gene amplification and immunohistochemistry 2+ or 3+ [Cohort 1] and 0 or 1+ [Cohort 2] ), locally|||||||||||||||

|advanced, unresectable or metastatic BTC (gallbladder cancer, intra-/extra-hepatic chol-|||||||||||||||

|angiocarcinoma) who received prior gemcitabine-containing treatment (tx). Exploratory endpoints|||||||||||||||

|assessed at baseline (BL) and every 8 weeks included the Brief Pain Inventory short form, the visual|||||||||||||||

|analog scale (VAS), and analgesic opioid use. Results: Of the 80 patients with HER2+ BTC in Cohort 1|||||||||||||||

|who were assessed for primary efficacy (median age 64 yrs; 56% female), 1 (1%) had complete|||||||||||||||

|response (CR), 32 (40%) partial response (PR), 22 (28%) stable disease (SD), and 24 (30%) progressive|||||||||||||||

|disease (PD); 1 patient was not evaluable. Responders (CR or PR) generally reported improved pain|||||||||||||||

|scores and less pain interference with activities of daily living. Patients with PD generally had|||||||||||||||

|worsening pain scores and pain interference by time of best on tx score (BONT) (Table). Overall,|||||||||||||||

|patients who responded to zani reported improved quality of life (VAS scores) vs BL. Fewer patients|||||||||||||||

|with CR (0.0%; n=1) and PR (3.1%; n=32) increased opioid use overall post-BL vs patients with SD|||||||||||||||

|(9.1%; n=22) or PD (34.8%; n=23). Conclusions: Patients with HER2+ BTC who responded to zani|||||||||||||||

|reported less pain and pain interference compared with BL, further supporting the development of zani|||||||||||||||

|as a tx option for these patients, with the goal of improving patient outcomes. Clinical trial information:|||||||||||||||

|NCT04466891. Research Sponsor: Jazz Pharmaceuticals.|||||||||||||||

|Mean (SD) BL and change at time of BONT for pain severity and pain interference domains by|||||||||||||||

|tumor response.|||||||||||||||

||CR BL|CR BONT|PR BL|PR BONT|SD BL|SD BONT|PD BL|PD BONT|||||||

||(n=1)|(n=1)|(n=30)|(n=30)|(n=21)|(n=21)|(n=24)|(n=18)|||||||

|Worst pain in|4.0|24.0 2.1 (2.5) 21.9 (2.5) 2.4 (2.7) 20.4 (2.1) 2.3 (2.3) 1.8 (3.1)|||||||||||||

|last 24 hrs|||||||||||||||

|General|3.0|23.0 1.5 (2.5) 21.4 (2.5) 1.5 (2.0) 20.3 (1.7) 1.6 (2.6) 1.5 (2.7)|||||||||||||

|activities|||||||||||||||

|Mood|2.0|22.0 1.5 (2.6) 21.3 (2.4) 1.7 (2.2) 20.2 (2.2) 1.9 (2.7) 1.8 (3.3)|||||||||||||

|Walking|4.0|24.0 0.9 (2.0) 20.9 (2.0) 1.9 (2.5) 20.8 (2.2) 1.1 (2.4) 1.8 (2.7)|||||||||||||

|Normal work|3.0|23.0 1.4 (2.5) 21.3 (2.6) 1.8 (2.6) 0 (2.2) 2.0 (2.8) 1.1 (2.7)|||||||||||||

|Relations|3.0|23.0 0.7 (1.6) 20.5 (2.0) 1.4 (1.9) 20.7 (2.1) 1.5 (2.5) 1.2 (2.8)|||||||||||||

|Sleep|1.0|21.0 1.3 (2.2) 21.1 (1.8) 1.3 (2.3) 0.5 (1.9) 1.5 (2.3) 1.8 (3.4)|||||||||||||

|Life enjoyment|3.0|23.0 1.2 (2.3) 21.0 (2.4) 2.4 (3.1) 20.7 (3.0) 2.0 (2.5) 1.4 (2.9)|||||||||||||

|112s|HEPATOBILIARY CANCER|||||| |---|---|---|---|---|---|---|

||||||Median [IQR] OS and RFS|Median [IQR] OS and RFS|

||post-curative intent therapy were 4.6 [1.8, NR] and 1.8 [0.8, 6.3] years, respectively. OS and RFS were poorer for|post-curative intent therapy were 4.6 [1.8, NR] and 1.8 [0.8, 6.3] years, respectively. OS and RFS were poorer for|post-curative intent therapy were 4.6 [1.8, NR] and 1.8 [0.8, 6.3] years, respectively. OS and RFS were poorer for|post-curative intent therapy were 4.6 [1.8, NR] and 1.8 [0.8, 6.3] years, respectively. OS and RFS were poorer for|post-curative intent therapy were 4.6 [1.8, NR] and 1.8 [0.8, 6.3] years, respectively. OS and RFS were poorer for|post-curative intent therapy were 4.6 [1.8, NR] and 1.8 [0.8, 6.3] years, respectively. OS and RFS were poorer for|

||those in the ablation (median OS 3.2 years; RFS 1.2 years) and high to very high risk of recurrence group|those in the ablation (median OS 3.2 years; RFS 1.2 years) and high to very high risk of recurrence group|those in the ablation (median OS 3.2 years; RFS 1.2 years) and high to very high risk of recurrence group|those in the ablation (median OS 3.2 years; RFS 1.2 years) and high to very high risk of recurrence group|those in the ablation (median OS 3.2 years; RFS 1.2 years) and high to very high risk of recurrence group|those in the ablation (median OS 3.2 years; RFS 1.2 years) and high to very high risk of recurrence group|

||(median OS 4.3 years; RFS 1.4 years). Kendall's t rank correlation model in the overall group demonstrated a|(median OS 4.3 years; RFS 1.4 years). Kendall's t rank correlation model in the overall group demonstrated a|(median OS 4.3 years; RFS 1.4 years). Kendall's t rank correlation model in the overall group demonstrated a|(median OS 4.3 years; RFS 1.4 years). Kendall's t rank correlation model in the overall group demonstrated a|(median OS 4.3 years; RFS 1.4 years). Kendall's t rank correlation model in the overall group demonstrated a|(median OS 4.3 years; RFS 1.4 years). Kendall's t rank correlation model in the overall group demonstrated a|

||statistically significant positive correlation between RFS and OS (t = 0.66; 95% CI: 0.60-0.70; P , 0.001).|statistically significant positive correlation between RFS and OS (t = 0.66; 95% CI: 0.60-0.70; P , 0.001).|statistically significant positive correlation between RFS and OS (t = 0.66; 95% CI: 0.60-0.70; P , 0.001).|statistically significant positive correlation between RFS and OS (t = 0.66; 95% CI: 0.60-0.70; P , 0.001).|statistically significant positive correlation between RFS and OS (t = 0.66; 95% CI: 0.60-0.70; P , 0.001).|statistically significant positive correlation between RFS and OS (t = 0.66; 95% CI: 0.60-0.70; P , 0.001).|

||Conclusions: Based on real-world data, a significant positive correlation between RFS and OS supports RFS as|Conclusions: Based on real-world data, a significant positive correlation between RFS and OS supports RFS as|Conclusions: Based on real-world data, a significant positive correlation between RFS and OS supports RFS as|Conclusions: Based on real-world data, a significant positive correlation between RFS and OS supports RFS as|Conclusions: Based on real-world data, a significant positive correlation between RFS and OS supports RFS as|Conclusions: Based on real-world data, a significant positive correlation between RFS and OS supports RFS as|

||an efficacy marker and appropriate endpoint for pts in adjuvant HCC setting when OS data are immature.|an efficacy marker and appropriate endpoint for pts in adjuvant HCC setting when OS data are immature.|an efficacy marker and appropriate endpoint for pts in adjuvant HCC setting when OS data are immature.|an efficacy marker and appropriate endpoint for pts in adjuvant HCC setting when OS data are immature.|an efficacy marker and appropriate endpoint for pts in adjuvant HCC setting when OS data are immature.|an efficacy marker and appropriate endpoint for pts in adjuvant HCC setting when OS data are immature.|

||Research Sponsor: Merck & Co., Inc.|Research Sponsor: Merck & Co., Inc.|Research Sponsor: Merck & Co., Inc.|Research Sponsor: Merck & Co., Inc.|||

||RFS and OS.||||||

||||Prior Local Therapy|Prior Local Therapy|Risk of Recurrence|Risk of Recurrence|

||||Surgical|Local Ablation|Low to|High to Very|

|||Overall|Resection|Only|Intermediate|High|

|||N=611|N=508|N=103|N=343|N=137|

||RFS||||||

||n (%)|404 (66.1)|331 (65.2)|73 (70.9)|215 (62.7)|95 (69.3)|

||Median|1.8 [0.8,|1.9 [0.8, 6.9]|1.2 [0.6, 2.8]|2.1 [0.8, 8.2]|1.4 [0.6, 6.3]|

||[IQR]|6.3]|||||

||OS||||||

||n (%)|274 (44.8)|232 (45.7)|42 (40.8)|136 (39.7)|65 (47.4)|

||Median|4.6 [1.8,|5.0 [2.0, NR]|3.2 [1.7, NR]|6.2 [2.2, NR]|4.3 [1.2, NR]|

||[IQR]|NR]|||||

|||453 457|Poster Session Poster Session| |---|---|---|---|

|sided p,0.0001); PFS, 5.6 mo [95% CI 5.5-6.3] vs 3.7 mo [2.8-3.7] ; HR 0.52 [95% CI 0.41-0.65]; one-||||

|sided p,0.0001). The most common ($20%) grade $3 treatment-related adverse events for cam +||||

|rivo were hypertension (37.5%) and increased AST (16.5%) vs palmar-plantar erythrodysesthesia||||

|3 (95% confidence interval [CI] 4.9, 7.8) months and in CP-B7 pts was 6.7 (95% CI 5.1, 8.7) months. Conclusions: Characteristics at Study Entry CP-B (n=123) CP-B7 (n=84) All pts (N=1005) Asian/non-Asian, % 46/54 55/45 55/45 ECOG performance status ‡2, % 13 12 6 BCLC stage B/C, % 11/73 12/75 13/62 Alcohol use, % 42 40 25 Hepatitis B, % 27 30 38 Hepatitis C, % 23 23 24 Vascular invasion, % 43 57 34 Metastases, % 50 45 59 Initial regorafenib dose as 160/120/80 mg per day, % 9/18/15 6/13/10 47/11/40 Median time from initial uHCC diagnosis to regorafenib start, months 17.4 17.1 24.7 syndrome (15.2%) for sor. This analysis evaluated PROs stratified by age: ,65 yo (baseline, overall cam + rivo n=191, sor n=210) or $65 yo (baseline, overall cam + rivo n=81, sor n=61). Methods: < 65 Years Old ‡65 Years Old cam + rivo n=191 sor n=210 cam + rivo n=81 sor n=61 Parameter mTTD, mo HR (95 % CI); p-value c mTTD, mo HR (95 % CI); p-value c HRQoL/GHS a NR NR 0.97 (0.69, 1.38); p=0.44 7.4 6.5 1.09 (0.61, 1.92); p=0.39 Fatigue a 14.8 6.4 0.76 (0.55, 1.05); p=0.05 3.7 4.6 1.01 (0.60, 1.71); p=0.48 Pain a NR 12.9 0.91 (0.64, 1.30); p=0.30 11.2 4.6 0.56 (0.32, 0.98); p=0.02 Appetite loss a NR NR 0.86 (0.59, 1.25); p=0.21 8.3 6.8 0.80 (0.45, 1.41); p=0.22 Fatigue b NR 5.6 0.73 (0.53, 1.03); p=0.03 3.7 4.4 0.92 (0.54, 1.55); p=0.37 Jaundice b 15.9 NR 1.78 (1.14, 2.75); p=0.01 6.7 11.1 2.0 (1.06, 3.81); p=0.02 Pain b NR NR 1.10 (0.73, 1.63); p=0.33 12.9 6.8 0.47 (0.24, 0.91); p=0.01|Ethnicity: Latino White (83%), Non-Latino White (14%), Black (3%). Etiology: HCV (78 %) EtOH (50%), NASH (19%), and HBV (3%). ALBI Grade: I (6%), II (50%), III (44%). First line treatment in CPB: Sorafenib (86%), Nivolumab (8%), Lenvatinib (6%). Sorafenib was used across all ALBI grades, while Total N (%) ALBI I N (%) ALBI II N (%) ALBI III N (%) Patient Cohort (n) (%) 36 2 18 16 Age (median, range) (Years) 59, 50-71 58.5, 55-62 58.5, 51-71 59.5, 50-69 Sex Male 31 (86%) 2 (100%) 14 (78%) 15 (94%) Female 5 (14%) 0 (0%) 4 (22%) 1 (6%) Ethnicity Latino White 30 (83%) 1 (0%) 15 (83%) 14 (86%) Non-Latino White 5 (14%) 0 (0%) 3 (17%) 2 (14%) Black 1 (3%) 1 (50%) 0 (0%) 0 (0%) Etiology of Cirrhosis HBV 1 (3%) 0 (0%) 1 (6%) 0 (0%) HCV 28 (78%) 2 (100%) 14 (78%) 12 (75%) ETOH 18 (50%) 2 (100%) 8 (44%) 8 (50%) NASH 7 (19%) 0 (0%) 4 (22%) 3 (19%) First-Line Treatment Sorafenib 31 (86%) 2 (100%) 13 (72%) 16 (100%) Lenvatinib 2 (6%) 0 (0%) 2 (11%) 0 (0%) Nivolumab 3 (8%) 0 (0%) 3 (17%) Results: A total of 131 patients were analyzed. 119 patients (90.8%) were male, with a median age of 70 years [35; 88]; 40 patients (31%) had performance status (PS) $ 1. 103 patients (79%) had cirrhosis; 61 patients (46.6%) had portal hypertension. 49 patients (37.4%) had metastatic HCC and 52 patients (40.6%) had portal vein thrombosis at diagnosis. The mean initial level of alpha-fetoprotein was 5,212.8 ng/mL (SD: 18,681.8). 36 patients (27.5%) received only atezolizumab. 41 patients were Multivariate analysis of OS in patients with advanced HCC. HR p Initial level of alpha-fetoprotein 1.00 (1.00-1.00) 0.007 First two cycles of ICI infusion after 1 pm 2.29 (1.27-4.14) 0.005 PS ‡ 1 2.29 (1.22-4.28) 0.009 0 (0%) Monotherapy by atezolizumab 2.46 (1.29-4.68) 0.006|Ethnicity: Latino White (83%), Non-Latino White (14%), Black (3%). Etiology: HCV (78 %) EtOH (50%), NASH (19%), and HBV (3%). ALBI Grade: I (6%), II (50%), III (44%). First line treatment in CPB: Sorafenib (86%), Nivolumab (8%), Lenvatinib (6%). Sorafenib was used across all ALBI grades, while Total N (%) ALBI I N (%) ALBI II N (%) ALBI III N (%) Patient Cohort (n) (%) 36 2 18 16 Age (median, range) (Years) 59, 50-71 58.5, 55-62 58.5, 51-71 59.5, 50-69 Sex Male 31 (86%) 2 (100%) 14 (78%) 15 (94%) Female 5 (14%) 0 (0%) 4 (22%) 1 (6%) Ethnicity Latino White 30 (83%) 1 (0%) 15 (83%) 14 (86%) Non-Latino White 5 (14%) 0 (0%) 3 (17%) 2 (14%) Black 1 (3%) 1 (50%) 0 (0%) 0 (0%) Etiology of Cirrhosis HBV 1 (3%) 0 (0%) 1 (6%) 0 (0%) HCV 28 (78%) 2 (100%) 14 (78%) 12 (75%) ETOH 18 (50%) 2 (100%) 8 (44%) 8 (50%) NASH 7 (19%) 0 (0%) 4 (22%) 3 (19%) First-Line Treatment Sorafenib 31 (86%) 2 (100%) 13 (72%) 16 (100%) Lenvatinib 2 (6%) 0 (0%) 2 (11%) 0 (0%) Nivolumab 3 (8%) 0 (0%) 3 (17%) Results: A total of 131 patients were analyzed. 119 patients (90.8%) were male, with a median age of 70 years [35; 88]; 40 patients (31%) had performance status (PS) $ 1. 103 patients (79%) had cirrhosis; 61 patients (46.6%) had portal hypertension. 49 patients (37.4%) had metastatic HCC and 52 patients (40.6%) had portal vein thrombosis at diagnosis. The mean initial level of alpha-fetoprotein was 5,212.8 ng/mL (SD: 18,681.8). 36 patients (27.5%) received only atezolizumab. 41 patients were Multivariate analysis of OS in patients with advanced HCC. HR p Initial level of alpha-fetoprotein 1.00 (1.00-1.00) 0.007 First two cycles of ICI infusion after 1 pm 2.29 (1.27-4.14) 0.005 PS ‡ 1 2.29 (1.22-4.28) 0.009 0 (0%) Monotherapy by atezolizumab 2.46 (1.29-4.68) 0.006||

|454 458|Poster Session Poster Session|455|Poster Session|

|Characterization of outcomes and genomic alterations (GA) in combined|Real-world testing, treatment patterns, and outcomes following liquid bi-|Real-world testing, treatment patterns, and outcomes following liquid bi-||

|hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA). First Author:|opsy in advanced cholangiocarcinoma. First Author: Amit Mahipal, University|opsy in advanced cholangiocarcinoma. First Author: Amit Mahipal, University||

|Jaime Haro-Silerio, Baylor College of Medicine, Houston, TX|Hospitals Cleveland Medical Center, Cleveland, OH|||

|||Background: Cholangiocarcinoma (CCA) is an aggressive cancer with a poor prognosis.|Background: Cholangiocarcinoma (CCA) is an aggressive cancer with a poor prognosis.|

|||Given failure rates of up to 27% of CCA tissue biopsies, liquid biopsy has become an|Given failure rates of up to 27% of CCA tissue biopsies, liquid biopsy has become an|

|||important tool to identify actionable molecular alterations. It is estimated tissue-based|important tool to identify actionable molecular alterations. It is estimated tissue-based|

|||testing identifies IDH1 mutations and FGFR2 fusions in 12% and 9% of patients with|testing identifies IDH1 mutations and FGFR2 fusions in 12% and 9% of patients with|

|||advanced CCA (aCCA), respectively. Here we examined the rate of molecular alteration|advanced CCA (aCCA), respectively. Here we examined the rate of molecular alteration|

|||detection using circulating tumor DNA (ctDNA) testing, treatment patterns in aCCA, and|detection using circulating tumor DNA (ctDNA) testing, treatment patterns in aCCA, and|

|||outcomes for patients receiving ivosidenib following ctDNA-detected IDH1 mutations.|outcomes for patients receiving ivosidenib following ctDNA-detected IDH1 mutations.|

|novo aBTC (n=481, 82.9%) or recurrent aBTC (n=99, 17.1%) with median follow-up time of 10.4 (interquartile range: 6.4, 17.5) and 12.0 (interquartile range: 6.3, 21.9) months, 25.0% had portal vein tumor thrombus and 72.0% had advanced disease (M1/N1) at diagnosis. Radiographic washout was seen in 55.9%. Elevation of CA19-9, AFP, and both was in 42.5, 57.5, and 30.0%. Cirrhosis at diagnosis was 35.0%. Pts who underwent surgery (n=10) had significant OS benefit (55.6 vs. 14.1 m, p,0.001). Y90 (n=4)/ radiation therapy (n=10) provided significant OS benefit in pts who did not undergo surgery (23.3 vs 10.9 m; p=0.012). 34 pts received 1st line systemic therapy: 10 pts received gemcitabine/cisplatin (GC) combined with immunotherapy (GCI): GC + nivolumab (n=5), durvalumab (n=3), or atezolizumab/bevacizumab (AB, n=2). GCI was compared to other regimens (OR, n=24) including chemotherapy alone (GC, FOLFIRI, FOLFOX), HCC-directed therapy alone (AB, lenvatinib, nivolumab), or chemotherapy plus lenvatinib or bevacizumab|Methods: Real-world data was sourced from GuardantINFORM, which comprises ag-gregated commercial payer health claims and de-identified records from .330,000 patients with clinical ctDNA testing via Guardant360 (G360), from 2014 to 2023. Patients with aCCA and .1 treatment claim after G360 results were included (N=1726). Patient outcomes were assessed via real-world time to treatment discontinuation (rwTTD), real-world time to next treatment (rwTTNT), and real-world overall survival (rwOS), all assessed in months. Log rank test was used to compare Kaplan-Meier survival curves. Results: Of 1495 patients with .1 ctDNA alteration detected, a guideline-recommended biomarker was identified in 18% of patients. In patients with intrahepatic CCA (n=403), 11% had an IDH1 mutation, 9% an FGFR2 fusion, 1% MSI-H detected, 1% BRAF V600E mutation, ,1%|Methods: Real-world data was sourced from GuardantINFORM, which comprises ag-gregated commercial payer health claims and de-identified records from .330,000 patients with clinical ctDNA testing via Guardant360 (G360), from 2014 to 2023. Patients with aCCA and .1 treatment claim after G360 results were included (N=1726). Patient outcomes were assessed via real-world time to treatment discontinuation (rwTTD), real-world time to next treatment (rwTTNT), and real-world overall survival (rwOS), all assessed in months. Log rank test was used to compare Kaplan-Meier survival curves. Results: Of 1495 patients with .1 ctDNA alteration detected, a guideline-recommended biomarker was identified in 18% of patients. In patients with intrahepatic CCA (n=403), 11% had an IDH1 mutation, 9% an FGFR2 fusion, 1% MSI-H detected, 1% BRAF V600E mutation, ,1%||

|respectively. Mean (SD) age was 64.6 (11.2) and 66.8 (10.4) years, with 45.7% and 54.5% with mPFS of 7.0 vs. 2.9 m (p=0.014) showing significant PFS benefit. Pts who received GCI|ERBB2 amplification and ,1% RET fusion. Testing was performed prior to first-line|ERBB2 amplification and ,1% RET fusion. Testing was performed prior to first-line||

|male in the de novo and recurrent aBTC groups, respectively. Most patients were white trended to better OS compared to OR (18.9 vs. 12.0 m, p=0.380). 2 pts treated with GC+AB had|therapy, after first-line therapy and after second-line therapy in 34%, 46% and 21% of|therapy, after first-line therapy and after second-line therapy in 34%, 46% and 21% of||

|(77.6%). The most frequent site of primary tumor diagnosis was single-site intrahepatic complete responses to date at 36.0 and 14.0 m. Of 31 pts who underwent GA testing, the 2|patients respectively. Gemcitabine and cisplatin represented the most common first-line|patients respectively. Gemcitabine and cisplatin represented the most common first-line||

|(overall 62.8%, de novo 66.7%, recurrent 43.4%). In the 12 months prior to index date, most frequent GAs were TP53 (38.7%) and TERT (35.5%) mutations. Neither impacted OS:|therapy (48%). FOLFOX (21%), gemcitabine and cisplatin (13%), and capecitabine (11%)|therapy (48%). FOLFOX (21%), gemcitabine and cisplatin (13%), and capecitabine (11%)||

|38.5% of patients had biliary obstruction, 30.2% had biliary stents, 29.3% had jaundice, TP53 15.8 vs. 17.6 m (p=0.746); TERT 9.8 vs. 23.3 m (p=0.355). Conclusions: GCI had survival|were the most common second-line therapies. Among ivosidenib-naïve patients with an|were the most common second-line therapies. Among ivosidenib-naïve patients with an||

|and 17.1% had nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Common comorbidities included cardiovascular disease (50.9%), obesity (46.8%), and diabetes (35.2%). The most common 1L CT was GemCis followed by Gem for both the de novo benefit compared to OR in cHCC-CCA. Pts who present with early stage of disease should be evaluated early for surgical resection or maximize local therapy in the case of nonresectable disease to improve survival. Research Sponsor: None.|IDH1 mutation, 58 (20%) started therapy within 90 days of ctDNA test: 36% received ivosidenib, 57% received chemotherapy, 7% received other therapy. Patients with IDH1 mutations treated with ivosidenib (n=21) had numerically improved rwTTD and rwTTNT|IDH1 mutation, 58 (20%) started therapy within 90 days of ctDNA test: 36% received ivosidenib, 57% received chemotherapy, 7% received other therapy. Patients with IDH1 mutations treated with ivosidenib (n=21) had numerically improved rwTTD and rwTTNT||

|(n=355, 73.8% and n=36, 7.5%) and recurrent groups (n=58, 58.6% and n=26, 26.3%),|compared to those receiving chemotherapy (n=33) [rwTTD: 4.6 (95% CI:2.6-8.6) vs 2.8|compared to those receiving chemotherapy (n=33) [rwTTD: 4.6 (95% CI:2.6-8.6) vs 2.8||

|Initial Staging|Early 12 (28.0%); Advanced 28 (72.0%): lymphadenopathy 20 (50.0%),|||

||lung 8 (20.0%), bone 5 (12.5%), peritoneum 5 (12.5%), others 14 (35.0%)|||

|Etiology (n=26)|Hepatitis C 10 (38.4%), hepatitis B 7 (26.9%), metabolic syndrome 5 (19.2%),|||

||EtOH 1 (3.9%); hemochromatosis 1 (3.9%), Other 2|||

||(7.7%, immunosuppression, Hepatitis C+EtOH)|||

|PFS on 1st line therapy|6.5 vs 2.8 m (p=0.022)|||

|CA 19-9+AFP elevated (n=11) vs||||

|One elevation+both negative (n=18)||||

|OS Washout (n=19) vs No Washout (n=15)|16.6 v.15.8 m (p=0.702)|||

|Mutations (n=31)|TP53 12 (38.7%), TERT 11 (35.5%),|||

||CTNNB1 5 (16.1%), IDH1 4 (12.9%)|||

|Key results.|||||| |---|---|---|---|---|---|

|||Race||Ethnicity||

|||Black/||||

|||African||Non-||

||White|American|Other|Hispanic|Hispanic|

||(n=66)|(n=25)|(n=21)|(n=94)|(n=23)|

|Sex, male, n (%)|37 (56)|11 (44)|9 (43)|46 (49)|11 (48)|

|Median age at BL, (P25-P75), y|64 (57-69) 67 (60-69) 66 (61-73) 65 (58-70) 65 (57-72)|||||

|Received testing for FGFR2 alterations, n (%)|64 (|||||

|Methods: We queried the National Cancer Database (NCDB) for patients with IHC be-||||||| |---|---|---|---|---|---|---|

|tween 2004-2020. Patients with inadequate data quality, carcinoma in situ, other primary|||||||

|cancers prior to IHC diagnosis, distant metastasis (M1), unknown M status (MX), and no|||||||

|treatment were excluded. Lymph node involvement was categorized using clinical N stage|||||||

|to reflect clinical decision-making. Due to AJCC staging updates and coding limitations,|||||||

|subgroup analysis of patients with multifocal disease (T2bNXM0 in the 7 th AJCC edition)|||||||

|was confined to 2010-2017. A two-sided Cochran-Armitage test was used to evaluate|||||||

|time trends and Kaplan Meier methods were used to summarize overall survival (OS).|||||||

|Results: Of 11,368 patients treated for IHC without distant metastasis between 2004-|||||||

|2020, 2,467 / 10,183 (24%) with clinical lymph node staging had positive nodes; the|||||||

|subgroup with multifocal disease comprised 1,384 patients staged T2bNXM0 between|||||||

|2010-2017. Overall, 36% of patients received formal resection as first treating modality|||||||

|and 59% received systemic or radiation therapy first. The use of perioperative chemo-|||||||

|therapy in combination with formal resection increased from 39% pre 2010 to 70% in|||||||

|2018-2020 (p,0.001), most often delivered post-operatively: 49% received adjuvant, 13%|||||||

|neoadjuvant, and 8% both in 2018-2020. Among those with clinically positive lymph|||||||

|nodes, there was a decreasing trend in upfront resection (p,0.001) and an increase in|||||||

|systemic or radiation therapy first (p,0.001). Similarly, in the multifocal disease sub-|||||||

|group analysis, the proportion of upfront formal resection trended down from 33% in 2010|||||||

|to 12% in 2017 (p,0.001). Across the entire cohort, median OS improved from 16 months|||||||

|(IQR 15, 18) to 27 months (IQR 26, 29) for patients diagnosed 2018-2019 compared|||||||

|to ,2010. Conclusions:|||||||

|||||463||Poster Session|

|||||||Results: Our|

|||||cohort had 144 patients with median age of diagnosis (dx) of 65 years, 81 % Caucasians, 81%|||

|||||males, 5% and 51% with hepatitis B and C, respectively; 24% and 21% ascites (As) and|||

|||||hepatic encephalopathy (HE) at dx, respectively; 72% (n=125) had just one procedure (24|||

|||||had two planned procedures which were considered as 1), 12% (17) and 1% (2) had second|||

|||||and third procedures for recurrence, respectively. Immune checkpoint inhibitor (ICI) and|||

|||||other systemic therapy (tyrosine kinase inhibitor (TKI) or ramucirumab (Ram)) were given to|||

|||||27% (5 before and 34 after TARE) and 24% (5 before and 30 after TARE), respectively. Other|||

|||||HCC-related BLC includes the number of lesions 1 vs 2-3 vs multiple = 45% vs 33% vs 22%;|||

|||||single lobe vs two lobes = 66 vs 33%; portal vein tumor thrombosis (PVTT) = in main portal|||

|||||vein vs. non-main veins (left or right or lower level) vs no PVTT = 14% vs 10% vs 76%. Median|||

|||||overall survival (OS) and time to recurrence after the first TARE (TTR) were 11 and 4 months|||

|Cox regression model showing association between baseline frailty status and OS among older adults with hepatocellular cancer. Variable Hazards Ratio 95% CI P-value|(m), respectively. The only BLC that significantly influenced TTR was As (3 vs 4 m, p=0.008). Factors impacting OS were discussed in the table. Follow-up imaging (median = 3m) was available for response evaluation in 107/144 (indeterminate response (IR) reported in 25),||||||

|Frailty Category -Robust -Pre-frail -Frail|Ref 2.03 2.60|-0.76-5.41 1.03-6.54|-0.15 0.04|and the response noted was reflective of OS (objective response vs. disease progression vs indeterminate, 22 vs 6 vs 8.5 m, p,0.001). Conclusions: Careful patient selection based on BLC and the use of ICI (before or after) could improve the outcomes in HCC patients treated|||

|Age* Etiology -Non-viral|1.00 Ref|0.96-1.05 -|0.90 -|with TRAE. Larger prospective studies are needed to validate the study. Research Sponsor: None.|||

|-Unknown vs Non-viral -Viral vs Non-viral|0.68 0.50|0.31-1.48 0.26-0.99|0.33 0.04|Characteristic|Populations Tested|Overall Survival (OS) in Months (p-value)|

|Child Pugh -A -B -C Cancer Stage -I/II -III/IV vs I/II -NA vs I/II|Ref 1.80 11.3 Ref 1.50 0.35|-0.93-3.49 2.34-55.45 -0.74-3.08 0.04-2.88|-0.08 0.002 -0.26 0.33|As before TARE HE Number of lesions at baseline PVTT ICI use, anytime & in relation to TARE TKI or Ram use, anytime & in|Yes vs no Yes vs no 1 vs . 1 Main portal vein vs non-main veins vs none Yes vs no & before vs after vs. never|14 vs 7 (0.001) 14 vs 7 (0.001) 14 vs 9 (0.02) 8 vs 22 vs 10 (0.04) 23 vs 8 (0.002) & 23 vs 22 vs 8 (0.01) 14 vs 10 (0.4) & 5 vs 14 vs 10 (0.04)|

|||||relation to TARE|||

||||Control||| |---|---|---|---|---|---|

||||Cohort|4R Cohort||

||||%|%||

||||N=42|N=17|P value|

||Care Delivery|Emotional distress or worry assistance referral|36|76|0.005|

|||Primary care provider referral|76|88|0.3|

|||Practical, financial, or insurance help referral|43|59|0.2|

|||Receipt of side-effect information before starting treatment 74|Receipt of side-effect information before starting treatment 74|Receipt of side-effect information before starting treatment 74|Receipt of side-effect information before starting treatment 74|

|||Receipt of printed liver cancer information|67|100|0.004|

|||Receipt of information about cancer.net|38|94|0.0001|

||Patient Self-|Understand the goal of care|79|100|0.04|

||Management|||||

|||Able to understand, participate in care|60|88|0.03|

|||Felt in control of my care|76|100|0.02|

|||Able to manage and organize one's care|36|82|0.001|

|466|Poster Session|||||

|Single-institutional analysis of radiotherapy and orthotopic liver transplant||||||

|for patients with unresectable cholangiocarcinoma. First Author: Meng-Lun||||||

|Hsieh, Department of Radiation Oncology, University of Texas Southwestern Medical||||||

|Center, Dallas, TX||||||

|22 months; p=0.36), PFS (median 14.2 vs. 11 months; p=0.09), and 1-year LC (73.2% vs. 66.7%;||||||

|p=0.10). However, SBRT appeared to have lower proportions of acute grade 3+ (9.1% vs.||||||

|33.3%) and chronic grade 3+ toxicities (22.7% vs. 33.3%). Four patients with early stage||||||

|perihilar or ICC underwent SBRT as successful bridge to transplant, with no evidence of disease||||||

|progression at 5.4 months. An additional 2 out of 8 patients were removed from protocol due to||||||

|disease progression and 2 others remain on protocol, awaiting OLT. Conclusions: In our series||||||

|of unresectable cholangiocarcinoma, we found no difference in OS, PFS, and LC for patients||||||

|treated with SBRT vs. CRT, although the former appeared to have lower toxicity and a trend||||||

|towards improved PFS. Further research is needed to compare SBRT and CRT as definitive||||||

|treatment or bridge to OLT for patients with unresectable cholangiocarcinoma. Research||||||

|Sponsor: None.||||||

|). In multivariate analyses, preoperative ENBD and/or ERBD and elevated serum CA19-9 level (.200 ng/mL) were prognostic factors for intrahepatic recurrence, with hazard ratios (HR) of 2.154 (95% confidence interval (CI) 0.893-7.626, P = 0.080) and 3.647, (95% confidence interval (CI) 1.660-8.011, P = 0.001). Conclusions: 469 Markov model was built based on five global, multicenter, open-label, phase III ran-Poster Session Methods: A domized trials (Himalaya, IMbrave150, ORIENT-32, CARES-310, LEAP-002) to investigate the cost-effectiveness of tremelimumab plus durvalumab (STRIDE), atezolizumab plus bevacizumab (A+B), sintilimab plus bevacizumab biosimilar (IBI305) (S+B), camreli-zumab plus rivoceranib (C+R) and pembrolizumab plus lenvatinib (P+L). Three disease states were included: progression free survival (PFS), progressive disease (PD), and Poster Session 471 Poster Session Primary objectives in phase Ib were safety, tolerability, and determination of the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Results: As of 17-Aug-2023, six pts (5 cholangiocarcinoma, 1 gallbladder carcinoma) were enrolled and treated with tinengotinib 8 mg QD plus atezo (n=3) or tinengotinib 10 mg QD plus atezo (n=3). Median age was 62.0 years (range 47-75), 83.3% had ECOG performance status of 1, 83.3% had stage IV disease, 50% had $ 3 lines of prior antineoplastic therapies, and 50% had prior immunotherapy. No DLT was observed in these two dose levels. Treatment-related adverse events (TRAEs) were reported in 6 (100%) pts, including Grade (Gr)1-2 for 6 pts, Gr 3 in 2 pts. No Gr 4-5 TRAE. The most common TRAEs ($ 50%) included hypertension, palmar-plantar erythrodysesthesia syndrome, blood bilirubin increased, proteinuria, hypertriglyceridemia and platelet count decreased. Two pts achieved partial response (PR). One prior immunotherapy naïve pt had a tumor reduction of 48.0% lasting for more than 5 months (tinengotinib 8 mg QD plus atezo). Another pt with prior immunotherapy (sintilimab), target therapy (donafenib) and chemotherapy death. 470 had a tumor reduction of 39.|| |---|---|

|Results from a phase 2 study of triplet blockade of the IL-27, PD-(L)1, and|Pivotal single-arm, phase 2 trial of tasurgratinib for patients with fibroblast|

|VEGF pathways with casdozokitug (casdozo, SRF388) in combination with|growth factor receptor (FGFR)-2 gene fusion-positive cholangiocarcinoma|

|atezolizumab (atezo) and bevacizumab (bev) in patients with unresectable,|(CCA). First Author: Junji Furuse, Kanagawa Cancer Center, Yokohama, Japan|

|locally advanced, or metastatic hepatocellular carcinoma (uHCC). First Au-thor: Daneng Li, City of Hope National Comprehensive Cancer Center, Duarte, CA|Background: CCA represents ~3% of all gastrointestinal malignancies globally; it is particularly prevalent in Asian countries. Additionally, FGFR2 gene fusions occur in ~13%|

|Background: Casdozo is the first in class and only clinical-stage IL-27 targeting antibody,|of intrahepatic CCA cases. Tasurgratinib (E7090) is an orally available selective inhibitor of|

|which neutralizes IL-27 in the tumor microenvironment and stimulates antitumor re-|FGFR 1-3; the recommended dose is 140 mg per day per the dose-escalation part of a first-|

|sponse. A phase (Ph) 1 study demonstrated a favorable safety profile and antitumor|in-human phase 1 study. In this pivotal phase 2 study, this regimen was evaluated in|

|activity alone and in combination with PD-1 blockade in indications known to have high|patients (pts) with FGFR2 fusion-positive CCA. Methods: Japanese and Chinese pts with|

|levels of IL-27 pathway activation, such as HCC (NCT04374877). Casdozo induced in-|surgically unresectable advanced or metastatic CCA were treated with tasurgratinib|

|creases in serum IFN-g and NK cell gene activation, indicating an immune response and|140 mg PO daily. FGFR2 gene fusion was confirmed by fluorescence in situ hybridization|

|reversal of IL-27-mediated immune suppression. IHC evaluation of HCC commercial tissue|performed in central laboratories; $ 1 prior chemotherapy regimen including a|

|microarrays revealed that most HCC samples express the target: IL-27+ tumor-associated|gemcitabine-based combination was required; pts treated with FGFR2 inhibitors were|

|macrophages (TAMs, internal data). We present the safety and antitumor activity of this|excluded. The primary endpoint was objective response rate (ORR; complete response [CR]|

|immunoregulatory cytokine antagonist given in combination with atezo/bev in uHCC in the|+ partial response [PR]). Secondary endpoints included duration of response (DOR), time to|

|open-label phase of a randomized Ph 2 trial. Methods: Patients (pts) with untreated uHCC|response (TTR), disease control rate (DCR; CR + PR + stable disease [SD]), clinical benefit|

|received casdozo 10 mg/kg, atezo 1200 mg, and bev 15mg/kg IV every 3 weeks. Primary|rate (CBR; CR + PR + SD lasting $ 23 weeks), progression-free survival (PFS), overall|

|Background: Claudin 18 isoform 2 (CLDN18.2) belongs to a family of tight junction|First Author: Anwaar Saeed, University of Pittsburgh Medical Center, Pittsburgh, PA|First Author: Anwaar Saeed, University of Pittsburgh Medical Center, Pittsburgh, PA||

|proteins with broad expression in gastric and gastroesophageal junction (GEJ), pan-|Background: Anti-VEGFR2 antibody (ramucirumab) has efficacy in gastric cancer (GC),|Background: Anti-VEGFR2 antibody (ramucirumab) has efficacy in gastric cancer (GC),||

|creatic, esophageal, and other solid tumors. Expression of CLDN18.2 in normal tissue is limited to the gastric mucosa, making it a promising antibody-drug conjugate (ADC)|both as monotherapy & in combination with paclitaxel based on the REGARD & RAINBOW trials that led to its FDA approvals in the 2 nd line setting. Preclinical data demonstrate|both as monotherapy & in combination with paclitaxel based on the REGARD & RAINBOW trials that led to its FDA approvals in the 2 nd line setting. Preclinical data demonstrate||

|therapeutic target. Currently, there are no approved therapies targeting CLDN18.2. EO-|significant tumor immune microenvironment modulatory effects from antiangiogenic|significant tumor immune microenvironment modulatory effects from antiangiogenic||

|3021 (also known as SYSA1801) is an ADC comprised of a fully human CLDN18.2 monoclonal antibody (mAb) specifically conjugated at glutamine 295 with a cleavable linker and MMAE with a homogenous drug-to-antibody ratio (DAR) of 2. In preclinical models, EO-3021 selectively delivers a potent cytotoxic MMAE payload directly to cancer cells expressing CLDN18.2, retains antibody-dependent cellular toxicity (ADCC) and complement-dependent cytotoxicity (CDC) activity, and exhibits a bystander effect. 1 In an ongoing Phase 1 study in China (NCT05009966), EO-3021 exhibited signs of anti-tumor activity in patients with gastric cancer and had an acceptable safety profile. 2 Outside of Greater China, EO-3021 is being evaluated by Elevation Oncology for the treatment of patients with advanced or metastatic solid tumors likely to express CLDN18.2, particularly gastric and GEJ adenocarcinomas. Methods: This is a Phase I, open-label, multi-center, dose escalation and expansion study to investigate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of EO-3021 in patients with solid tumors likely to express CLDN18.2 (NCT05980416). Patients whose tumors have progressed on or after standard therapy, or who are intolerable for available standard therapy are eligible for participation. Approximately 120 patients will be enrolled in this study. There are 4 planned dose levels in the dose finding portion of the study. Patients will receive EO-3021 intravenously (IV) once every three weeks until|agents, supporting the clinical study of dual VEGFR with immune checkpoint blockade. This has resulted in at least 7 FDA-approved combinations of anti-VEGF/VEGFR with anti-PD-1/ PD-L1 agents in lung, renal, endometrial & liver cancers. Recent data showed encouraging activity with ramucirumab plus nivolumab & other trials with pembrolizumab and durva-lumab in GC & esophageal adenocarcinoma. Notably, the addition of nivolumab to 2 nd line ramucirumab plus paclitaxel was evaluated in a multi-center phase I/II trial. Study pop-ulation consisted of 60% (26/43) harboring tumors positive for PD-L1 CPS $ 1. Results revealed encouraging efficacy (ORR 37.2%, 6-month PFS 46.5%) in the overall population. Median PFS and OS were found to be numerically higher in PD-L1 CPS $ 1 (6.4 months & 13.8 months respectively) compared to CPS-negative participants (5.1 months & 8.0 months), suggesting a predictive impact of PD-L1 CPS in this treatment setting. Methods: SWOG2303 is a national, randomized, open label, phase II/III trial to assess the efficacy and safety of nivolumab + paclitaxel + ramucirumab versus paclitaxel + ramu-cirumab in adult patients with advanced stage MSS/pMMR PD-L1 CPS $ 1 gastric and esophageal adenocarcinoma. Patients must have documented MSI and PD-L1 CPS status by standard of care tissue-based analysis, evaluable disease on imaging, and Zubrod per-formance status (PS) 0-1. They should also have clinical or radiographic progression or intolerance to frontline standard of care systemic therapy with PD-1 inhibitor containing fluoropyrimidine based chemotherapy regimen. Patients with HER2 positive disease are|agents, supporting the clinical study of dual VEGFR with immune checkpoint blockade. This has resulted in at least 7 FDA-approved combinations of anti-VEGF/VEGFR with anti-PD-1/ PD-L1 agents in lung, renal, endometrial & liver cancers. Recent data showed encouraging activity with ramucirumab plus nivolumab & other trials with pembrolizumab and durva-lumab in GC & esophageal adenocarcinoma. Notably, the addition of nivolumab to 2 nd line ramucirumab plus paclitaxel was evaluated in a multi-center phase I/II trial. Study pop-ulation consisted of 60% (26/43) harboring tumors positive for PD-L1 CPS $ 1. Results revealed encouraging efficacy (ORR 37.2%, 6-month PFS 46.5%) in the overall population. Median PFS and OS were found to be numerically higher in PD-L1 CPS $ 1 (6.4 months & 13.8 months respectively) compared to CPS-negative participants (5.1 months & 8.0 months), suggesting a predictive impact of PD-L1 CPS in this treatment setting. Methods: SWOG2303 is a national, randomized, open label, phase II/III trial to assess the efficacy and safety of nivolumab + paclitaxel + ramucirumab versus paclitaxel + ramu-cirumab in adult patients with advanced stage MSS/pMMR PD-L1 CPS $ 1 gastric and esophageal adenocarcinoma. Patients must have documented MSI and PD-L1 CPS status by standard of care tissue-based analysis, evaluable disease on imaging, and Zubrod per-formance status (PS) 0-1. They should also have clinical or radiographic progression or intolerance to frontline standard of care systemic therapy with PD-1 inhibitor containing fluoropyrimidine based chemotherapy regimen. Patients with HER2 positive disease are||

|disease progression or unacceptable toxicity. The expansion cohort will evaluate EO-|excluded as well as patients with prior significant immunotherapy related adverse events|excluded as well as patients with prior significant immunotherapy related adverse events||

|3021 in patients with gastric/GEJ adenocarcinoma. Provision of tumor samples (ar-|(iRAEs) that prompted permanent discontinuation of the PD-1 agent. Planned enrollment is|(iRAEs) that prompted permanent discontinuation of the PD-1 agent. Planned enrollment is||

|||224.||

|This is a multicenter, single arm, open-label, phase| |---|

|II trial including a total of 32 pts with T1-T2N0 EGA (including GEJ) with indication for|

|radical surgery. Enrolled pts will receive immunotherapy with durvalumab (1500 mg|

|Q4W) in parallel to 2 cycles FLOT (50 mg/m2 docetaxel, 85 mg/m2 oxaliplatin, 200 mg/|

|m2 calcium folinate and 2600 mg/m2 5FU, Q2W) induction followed by 3 cycles of|

|mFOLFOX (85 mg/m2 oxaliplatin, 200 mg/m2 calcium folinate, 400 mg/m2 5FU bolus|

|and 1600 mg/m2 5FU over 48h, Q2W) plus concomitant radiation (25 daily fractions with|

|2.0 Gy =|

|katchewan, Canada from 2000-2019 were evaluated. Cox proportional multivariate| |---|

|regression analyses was performed to determine factor correlated with inferior out-|

|comes. Results: 331 patients with median age of 74 yrs and M:F of 1:2 were identified.|

|92% had a pathological diagnosis of GBC & 80% had adenocarcinoma. 49% were|

|diagnosed .year 2010. 217 (66%) of those diagnosed with GBC were rural residents. 149|

|(45%) patients were referred to a cancer center. In patients with documented stage, 64%|

|had stage IV disease & .90% were symptomatic with a median time from the onset of|

|symptoms to the diagnosis of 7 months. Rural residents have a significantly high rate of|

|smoking history whereas urban residents have significantly high rates of pathological|

|diagnosis, low serum albumin and elevated platelet count. Median overall survival (OS)|

|of patients with stage I-III GBC was 20 months (95% CI:10.9-29.1) vs. 4.0 months (3.0-|

|5.0) with stage IV GBC (,0.001). No significant differences were noted in OS in relation|

|to residence and time-period of diagnosis. Patients who were not referred for a cancer|

|center had a median OS of 3 months (1.98-4.0) vs. 13 months (9.9-16.1), p,0.001.|

|Median disease-free survival (DFS) of patients with stage I-III GBC was 20 months (95%|

|CI: 10-30.1) with 5-year DFS of 36%. Patients with stage I-III GBC who received adjuvant|

|chemotherapy had 5-yr DFS of 43% vs. 33% without adjuvant chemotherapy (p=0.73). 5-|

|year DFS of urban patients was 25% vs. 42% of rural patients (p=0.016). On multivariate|

|analysis for patients with Stage I-III GBC, stage III disease, HR (hazard ratio), 2.63 (1.09-|

|6.34) and urban residence, HR, 2.20 (1.1-4.39) were correlated with inferior DFS whereas|

|for all patients, stage IV disease, HR, 3.02 (1.85-4.94); no referral to cancer center, HR,|

|2.64 (1.51-4.62); lack of surgery, HR, 1.63 (1.03-2.57); neutrophil:lymphocyte of .3.2,|

|HR, 1.57 (1.05-2.36); and age $70, HR, 1.51 (1.04-2.19) were correlated with inferior OS.|

|Methods: The National Cancer Database was used to identify patients diagnosed with FL-HCC from 2004-2019 using the histology code 8171 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, Chi-Square, ANOVA, and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 29 and statistical significance was set at a=0.05. Results: Of the 436 patients included, 241 (55%) had private insurance and 96 (22%) had Medicare. Patients with private insurance had a longer median survival (49 months) than patients with Medicare (18 months; p,.001) and Medicaid (26 months; p,.004);no significant survival difference existed between Medicare, Medicaid, and no insurance (39 months) (p's$.063). After controlling for age, income, tumor size, adjuvant therapy, receiving surgery, and surgical margins of primary site, private insurance was associated with an independent decrease in hazard (HR=.899; p=.004).Patients with private insurance received more surgery (68%) than those with Medicaid (50%), no insurance (48%), and Medicare (32%) (p's,.001); grade did not differ amongst insurance types (p=.069).Furthermore, patients with private insurance had more surgical margins of the primary tumor site without residual tumor (57%) compared to those with Medicaid (40%), no insurance (38%), and Medicare (23%) (p's,.001).While patients with Medicare presented with greater co-morbidities, age at diagnosis (67), tumor size (476 mm), positive regional lymph nodes (90), and days between diagnosis and treatment (45), patients with private insurance presented at a younger age (31) with fewer co-morbidities, smaller sized tumors (366 mm), and fewer days between diagnosis and treatment (26) (p's,.018). 441 Revisiting non-invasive diagnosis of hepatocellular carcinoma in clinical Poster Session reality. First Author: Andreas Teufel, Heidelberg University, Mannheim, Germany Background: Consequently, our study aims to assess the efficacy of imaging techniques in distinguishing between HCC, CCC, and cHCC-CC, highlighting its clinical significance. Methods: We conducted a database search to identify patients diagnosed with HCC, CCC, and cHCC-CC from June 2010 to September 2020. After implementing quality control measures, our study comprised 68 MRI scans from patients, including 30 with HCC, 23 with CCC, and 15 with cHCC-CC. Histological evidence confirming the diagnoses was obtained within a maximum of four weeks before or after the MRI scans. Subsequently, seven radiologists from Asia, Europe, North America, and South America, including abdominal imaging experts (AIEs) and non-abdominal imaging experts (NIEs) or trainees, independently and blindly assessed the MRI scans. They evaluated various MRI features and established a differential diagnosis encompassing HCC, CCC, and cHCC-CC. Results: The AIEs demonstrated high proficiency in utilizing MRI images exclusively for diagnosing HCC (70%-100%) and CCC (73.9%-91.3%). They significantly outperformed NIEs/trainees (all p values , 0.01), achieving accuracy rates of 26.7%-66.7% for HCC and 21.7%-60.9% for CCC. However, their ability to accurately distinguish cHCC-CC (6.7%-53.3%) was limited and comparable to NIEs/trainees (26.7%-46.7%). Additionally, there was greater con-sistency in MRI||| |---|---|---|

|Results of statewide demographics, cancer cases and linear regression analyses for examined|||

|variables.|||

|Factor|R|p-value|

|Race & Ethnicity|||

|Hispanic|0.39|0.003|

|Non-Hispanic Black|0.39|0.004|

|Non-Hispanic White|-0.55|< 0.0001|

|Asian|0.33|0.01|

|Socioeconomic Factors|||

|Uninsured|0.10|0.48|

|Foreign Born|0.45|0.0008|

|Smoker|0.17|0.18|

|Men Prev. Care|-0.37|0.006|

|Women Prev. Care|-0.30|0.03|

|Rural|-0.33|0.01|

|Obese|0.26|0.06|

|Real-world (RW) characteristics, treatment patterns, and outcomes of pa-|A single-center, real-world experience of atezolizumab plus bevacizumab as|A single-center, real-world experience of atezolizumab plus bevacizumab as|

|tients with cholangiocarcinoma (CCA) treated with pemigatinib. First Author:|first-line therapy in patients with unresectable hepatocellular carcinoma,|first-line therapy in patients with unresectable hepatocellular carcinoma,|

|Kim Saverno, Incyte Corporation, Wilmington, DE|including patients with advanced cirrhosis. First Author: Jay Parekh, UT Health|including patients with advanced cirrhosis. First Author: Jay Parekh, UT Health|

|endpoints were safety and tolerability, with key secondary endpoints being investigator-|survival (OS), and safety. The study was considered successful if the lower limit of the ORR|

|assessed ORR by RECIST1.1 and mRECIST. Results: As of August 9, 2023, 30 pts were|90% CI was . 15% in a planned population. Tumor responses were measured every|

|treated with casdozo/atezo/bev. Most pts were male (77%), Asian (67%), ECOG PS 1 (77%),|8 weeks by RECIST v1.1 per independent imaging review. Adverse event (AE) severity was|

|had viral etiology (53% HBV, 17% HCV), and had poor-risk disease as evidenced by|measured per CTCAE v4.03. Results: 63 Pts (Japanese: n = 28; Chinese: n = 35) were|

|metastatic spread (70%) and macrovascular invasion (23%). 47% had AFP $400ng/mL.|treated (median age: 55 years); 23 pts (37%) had received 1 prior regimen, all others had|

|Median time on therapy was 28 wks (3-69). Most treatment-related adverse events (TRAEs)|received $ 2. By the data cutoff date (March 15, 2023), 55 pts discontinued treatment|

|were low grade, with proteinuria (33%), fatigue (20%), decreased appetite (20%), and|(disease progression, n = 48; adverse events, n = 4; pt choice, n = 2; loss of clinical benefit, n|

|hypertension (20%) being most common. Grade 3/4 TRAEs occurred in 33%, with only|= 1). 19 Pts (30%) had a PR; 31 pts (49%) had SD and 13 (21%) had SD for $ 23 weeks. The|

|hypertension (13%) arising in $10% of pts. TRAEs resulting in any study drug discon-|ORR was 30% (2-sided 90% CI 20.7-41.0; 95% CI 19.2-43.0); the DCR was 79% (95% CI|

|tinuation was 20%. No deaths were attributed to study drugs. In the 29 response-evaluable|67.3-88.5); the CBR was 51% (95% CI 37.9-63.6). The median [m]TTR / DOR for re-|

|pts, 67% experienced any tumor shrinkage with a 38% ORR (3 CRs, 5 confirmed PRs, 3|sponders were 1.87 mos (IQR 1.77-2.10; range 1.6-14.7) / 5.6 mos (95% CI 3.7-9.3; range|

|unconfirmed PRs). In the 28 pts evaluable for mRECIST, ORR was 43% (n=12). More than|1.0+-14.8+). The mPFS / OS were 5.4 mos (95% CI 3.7-5.6) / 13.1 mos (95% CI 10.8-17.4).|

||||477|Poster Session| |---|---|---|---|---|

||||Second-line regorafenib in patients (pts) with unresectable hepatocellular|Second-line regorafenib in patients (pts) with unresectable hepatocellular|

||||carcinoma (uHCC) after progression on first-line atezolizumab plus bev-|carcinoma (uHCC) after progression on first-line atezolizumab plus bev-|

||||acizumab (Atezo-Bev): nosis of HCC; prior treatment with Atezo-Bev at least $ 2 cycles; Child-Pugh A; ECOG||

||||performance status 0-1. Eligible patients received regorafenib 160 mg once daily|performance status 0-1. Eligible patients received regorafenib 160 mg once daily|

||||3 weeks on/1 week off until progressive disease or intolerable toxicity. The primary|3 weeks on/1 week off until progressive disease or intolerable toxicity. The primary|

||||endpoint is progression-free survival (PFS). Secondary endpoints were objective re-|endpoint is progression-free survival (PFS). Secondary endpoints were objective re-|

||||sponse rate (ORR), disease control rate (DCR) according to the RECIST v1.1, overall|sponse rate (ORR), disease control rate (DCR) according to the RECIST v1.1, overall|

||||survival (OS) and treatment-related adverse event (TRAE). Results: Total 40 pts were|survival (OS) and treatment-related adverse event (TRAE). Results: Total 40 pts were|

||||recruited from Dec 2021 to May 2023. Pts characteristics were as follows: median age of|recruited from Dec 2021 to May 2023. Pts characteristics were as follows: median age of|

||||56 (range, 36-81); hepatitis B (77.5%), hepatitis C (10.0%), non-viral (12.5%); BCLC C|56 (range, 36-81); hepatitis B (77.5%), hepatitis C (10.0%), non-viral (12.5%); BCLC C|

||||stage (97.5%); and AFP $ 400 ng/ml (40.0%). As of the date of data cut-off (15 Aug|stage (97.5%); and AFP $ 400 ng/ml (40.0%). As of the date of data cut-off (15 Aug|

||||2023), the median follow-up duration was 6.6 mo (95% CI, 5.0-8.2). The median PFS was|2023), the median follow-up duration was 6.6 mo (95% CI, 5.0-8.2). The median PFS was|

||||3.5 mo (95% CI, 3.0-4.0). ORR and DCR were 10.0% and 82.5%. The median OS was 9.7|3.5 mo (95% CI, 3.0-4.0). ORR and DCR were 10.0% and 82.5%. The median OS was 9.7|

||||mo (95% CI, 8.3-11.1) and 6-month OS rate was 55.0%. The median OS since the start of|mo (95% CI, 8.3-11.1) and 6-month OS rate was 55.0%. The median OS since the start of|

||||prior Atezo-Bev was 16.6 mo (95% CI, 11.9-21.3). When stratified according to the|prior Atezo-Bev was 16.6 mo (95% CI, 11.9-21.3). When stratified according to the|

||||duration of prior Atezo-Bev (,4 cycles [n=10] vs. $4 cycles [n=30] ), pts with $4 cycles|duration of prior Atezo-Bev (,4 cycles [n=10] vs. $4 cycles [n=30] ), pts with $4 cycles|

||||of prior Atezo-Bev showed better median OS (not reached vs 3.6 mo; p=0.001) and ORR|of prior Atezo-Bev showed better median OS (not reached vs 3.6 mo; p=0.001) and ORR|

||||(13.3% vs 0%; p=0.009), while there was a trend for better median PFS (3.8 mo vs 2.5 mo;|(13.3% vs 0%; p=0.009), while there was a trend for better median PFS (3.8 mo vs 2.5 mo;|

||||p=0.107). The most common grade 3-4 TRAEs were thrombocytopenia (5.0%), palmar-|p=0.107). The most common grade 3-4 TRAEs were thrombocytopenia (5.0%), palmar-|

|plantar erythrodysesthesia (2.5%), and fatigue (2.5%). Conclusions: 478 Poster Session|||||

|The efficacy and safety of transarterial chemoembolization combined with|||||

|cadonilimab and lenvatinib for unresectable hepatocellular carcinoma: A|||||

|phase II clinical trial. First Author: Guo Liang, Department of Interventional Therapy,|||||

|Zhejiang Cancer Hospital, Hangzhou, China|||||

|77.1% (95% CI, 60.8-87.3) per RECIST v1.1 and 75.6% (95% CI, 59.5-86.0) per mRECIST. The|||||

|ORR and DCR were 35.0% (95% CI, 23.1-48.4) and 96.7% (95% CI, 88.5-99.6) according to|||||

|RECIST v1.1 and 85.0% (95% CI, 73.4-92.9) and 95.0% (95% CI, 86.1-99.0) according to|||||

|mRECIST. 9 patients (15.0%) achieved complete response per mRECIST. The incidence of|||||

|grade$3 treatment-related adverse events (TRAEs) was 68.9%. The incidence of grade$3|||||

|adverse events related to cadonilimab was 45.9%.The most common TRAEs included|||||

|thrombocytopenia, aspartate aminotransferase increased, and alanine aminotransferase in-|||||

|creased. Conclusions: Combination of TACE and cadonilimab plus len showed promising|||||

|efficacy and manageable toxicity in intermediate uHCC. Benefit of control on tumor pro-|||||

|gression after TACE and lasting survival can be expected. Clinical trial information:||8)|8)|8)|

|NCT05319431. Research Sponsor: Akeso.Inc.|||Median PFS, months (95% CI) 6-month PFS rate, % (95% CI)|7.7 (6.0-8.6) 67.6 (50.7-79.8)|

|Objective response rate, n (%) Complete response rate, n (%) Disease control rate,n (%) mDOR, mo (95% CI) mPFS,mo (95% CI)|RECIST v1.1 N=60 21 (35.0) 2 (3.3) 58 (96.7) 5.68 [2.89, NE] NR (8.64, NE)|mRECIST N=60 51 (85.0) 9 (15.0) 57 (95.0) 10.02 [5.59, NE] NR (8.64, NE)|Median OS, months (95% CI) 6-month OS rate, % (95% CI) Subgroups analysis on cORR, % (95% CI) TIGIT + PD-L1 + (n=13) PD-L1 -(n=6) TIGIT -PD-L1 + (n=8) PD-L1 -(n=13)|NR (9.7-NE) 86.2 (71.8-93.6) 69.2 (38.6-90.9) 66.7 (22.3-95.7) 25.0 (3.2-65.1) 38.5 (13.9-68.4)|

|6-month PFS rate (%) (95% CI)|77.1 (60.8, 87.3)|75.6 (59.5, 86.0)|||

|481|Poster Session| |---|---|

||We identified|

|all pts with HCC naïve to systemic therapy who received infusions of A/B and those who|all pts with HCC naïve to systemic therapy who received infusions of A/B and those who|

|received RT to the liver within 30 days of starting A/B until discontinuation from 1/1/2020|received RT to the liver within 30 days of starting A/B until discontinuation from 1/1/2020|

|until 2/2/2023. We assessed the real-world response rate (rwRR) determined from clinician|until 2/2/2023. We assessed the real-world response rate (rwRR) determined from clinician|

|impression after initiating A/B, safety outcomes, overall survival (OS), and time-to-|impression after initiating A/B, safety outcomes, overall survival (OS), and time-to-|

|progression (TTP) from initiation of A/B. Time-to-event outcomes were analyzed by the|progression (TTP) from initiation of A/B. Time-to-event outcomes were analyzed by the|

|Kaplan-Meier method with log-rank test and Cox proportional hazards modeling.|Kaplan-Meier method with log-rank test and Cox proportional hazards modeling.|

|Results: We identified 49 pts (n=34 control, n=15 RT) with advanced HCC receiving first-line|Results: We identified 49 pts (n=34 control, n=15 RT) with advanced HCC receiving first-line|

|A/B. Those who received RT were more likely to have alcoholic liver disease (p=0.013) and|A/B. Those who received RT were more likely to have alcoholic liver disease (p=0.013) and|

|were less likely to have ascites (p=0.04) but were otherwise balanced regarding demo-|were less likely to have ascites (p=0.04) but were otherwise balanced regarding demo-|

|graphics, prior locoregional therapies, presence of macrovascular invasion and extrahepatic|graphics, prior locoregional therapies, presence of macrovascular invasion and extrahepatic|

|spread, and baseline laboratories. The median RT dose was 63 Gy. The rwRR in the RT group|spread, and baseline laboratories. The median RT dose was 63 Gy. The rwRR in the RT group|

|was 73.3% (11/15) compared to 17.6% (6/34) in the control group (Risk Ratio (RR) 3.9, 95%|was 73.3% (11/15) compared to 17.6% (6/34) in the control group (Risk Ratio (RR) 3.9, 95%|

|CI 1.7-8.6, p,0.001). Two pts in the control group (5.8%) and one patient in the RT group|CI 1.7-8.6, p,0.001). Two pts in the control group (5.8%) and one patient in the RT group|

|(6.7%) experienced clinically significant bleeding (RR=1.1 95% CI 0.1-11.6). In the RT group,|(6.7%) experienced clinically significant bleeding (RR=1.1 95% CI 0.1-11.6). In the RT group,|

|three pts (20%) developed worsening liver dysfunction after completing RT, concerning for|three pts (20%) developed worsening liver dysfunction after completing RT, concerning for|

|possible radiation-induced liver disease. Six pts in the control group and one patient in the|possible radiation-induced liver disease. Six pts in the control group and one patient in the|

|RT group developed immune-related adverse events leading to discontinuation of A/B. The|RT group developed immune-related adverse events leading to discontinuation of A/B. The|

|median OS in the RT group was 14.4 mos and 10.8 mos in the control group (Hazard Ratio|median OS in the RT group was 14.4 mos and 10.8 mos in the control group (Hazard Ratio|

|(HR) death 0.49 (95% CI 0.20-1.22, p=0.12)). Median TTP was 6.4 months (mos) with RT|(HR) death 0.49 (95% CI 0.20-1.22, p=0.12)). Median TTP was 6.4 months (mos) with RT|

|compared to 5.8 mos in the control group (HR progression 0.72 (95%CI 0.35-1.46, p=0.36.|compared to 5.8 mos in the control group (HR progression 0.72 (95%CI 0.35-1.46, p=0.36.|

|+ pembro (n = 395) or len + pbo (n = 399). Median follow-up was 43.6 mo (range, 37.3-52.6), and| |---|

|treatment was ongoing in 25 (3.2%) pts. Median OS was 21.1 mo with len + pembro vs 19.0 mo|

|with len + pbo (HR, 0.836; 95% CI, 0.713-0.981). OS rates for len + pembro vs len + pbo were|

|43.4% vs 40.0% at 24 mo, 32.7% vs 24.3% at 36 mo, and 22.4% vs 15.3% at 48 mo. Median PFS|

|was 8.2 mo with len + pembro vs 8.1 mo with len + pbo (HR, 0.810; 95% CI, 0.692-0.949). PFS|

|rates for len + pembro vs len + pbo were 16.4% vs 9.7% at 24 mo and 14.1% vs 3.3% at 36 mo.|

|ORR was 26.3% for len + pembro vs 17.5% for len + pbo. Median DOR was 16.6 mo (range, 2.0+|

|to 45.3+) for len + pembro vs 10.4 mo (range, 1.9 to 37.0+) for len + pbo. Grade 3-5 treatment-|

|related adverse event (TRAE) rates were 62.8% in the len + pembro arm and 58.0% in the len +|

|pbo arm. No additional deaths due to TRAEs were reported. The most common TRAEs of any|

|grade in the len + pembro vs len + pbo arms were hypertension (43.8% vs 46.8%), diarrhea|

|(40.8% vs 34.2%), and hypothyroidism (40.0% vs 35.9%). Overall, 46.6% vs 55.4% of pts|

|Coformulated quavonlimab and pembrolizumab (pembro) in combination||||| |---|---|---|---|---|

|with lenvatinib (lenva) as first-line (1L) therapy for patients (pts) with|||||

|advanced hepatocellular carcinoma (HCC): Phase 2 KEYSTEP-004 study.|||||

|First Author: Lorenza Rimassa, Department of Medical Sciences, Humanitas University,|||||

|Pieve Emanuele & Humanitas Cancer Center, IRCCS Humanitas Research Hospital|||||

|Rozzano, Milan, Italy|||||

|or death) was 7.7 mo (range, 0.9-22.1), and 89 pts (77.4%) discontinued treatment, most|||||

|commonly due to progressive disease (39.1%). Confirmed ORR was 37.4% (95% CI, 28.5-46.9),|||||

|with 5 CRs (4.3%) and 38 PRs (33.0%). DCR was 79.1% (95% CI, 70.6-86.1). Median DOR was 10.6|||||

|mo (range, 1.2+ to 23.1+). Median PFS and OS were 8.2 mo (95% CI, 6.2-10.2) and 22.1 mo (95%|||||

|CI, 15.5-not reached), respectively; 12-mo PFS and OS rates were 32.2% and 65.2%, respectively.|||||

|Treatment-related adverse events (TRAEs) occurred in 109 pts (94.8%); most common ($25%)|||||

|were hypertension (35.7%) and diarrhea (27.8%). Grade 3-5 TRAEs occurred in 66 pts (57.4%);|||||

|most common ($5%) were hypertension (8.7%) and immune-mediated enterocolitis (7.0%). 8|||||

|pts (7.|||||

||PFS (nanvuranlat vs. placebo)|Cholangitis (nanvuranlat)|||

|FAS-R|0.50 (0.05-5.51)|0.28|2 (28.5%)|2 (28.5%)|

|(n = 11)|||||

|FAS-NR|0.58 (0.35-0.98)|0.02|8 (12.7%)|7 (11.1%)|

|(n = 94)|||||

|9 months (95%CI 2.6-4.6), R0 resection rate was 48.8% (20/41), and 2 pts underwent R1 resection. 9.1% (2/22) pts had a pCR and 22.7% (5/22) had an MPR. The most common grade 3/4 treatment-related adverse events (TRAEs) included neutropenia (31.7%), increased GGT (19.5%), leukopenia (12.2%). No grade 5 489 ongoing open-label, single-arm, phase II trial (Clinical Trial ID: NCT05757336), which Poster Session Methods: The study was an consisted of 2 parts: safety-run-in part, where pts received sintilimab (200mg/kg, iv, d1, Q3W) + bevacizumab (7.5mg/kg, iv, d1, Q3W) + gemcitabine (1000mg/m2, iv, d1, Q3W) and albumin-bound paclitaxel (125mg/m2, iv, d1, Q3W), followed by experimental part to evaluate the efficacy and safety of this strategy. The primary endpoint was safety and objective response rate (ORR) assessed by RECIST v1.1. Secondary objectives included disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Results:| |---|

|||493|Poster Session| |---|---|---|---|

|therapy (22.4 vs. 12.0 m, p=0.004), surgery (21.0 vs. 12.0 m, p=0.002), local therapy with RT/||||

|ablation/Y90 (excluding surgical pts, 20.6 vs. 11.6 m, p = 0.0001) had significantly longer OS.||||

|Median PFS (mPFS) without ERBB2-directed therapy for 1 st , 2 nd , and 3 rd line systemic therapy||||

|was 4.1, 3, and 2.2 m. mPFS with all ERBB2-directed therapy was 4.1 m, but that of gemcitabine||||

|(gem)-based plus trastuzumab (tt) and 5FU-based plus tt was 7.8 and 3.8 m (p=0.018). The||||

|most common concurrent-GA at MDA, any co-amps (72.7%; 19.2 vs. 20.3 m, p=0.69) and TP53 inactivating mutation (70.4%; 16.6 vs. 14.9 m, p=0.89), had no OS association; 3 rd most||||

|common co-GA found, CDK12 amp (46.4%), had a trend toward a better OS (19.2 vs. 14.3 m,||||

|p=0.089). FMI database showed ERBB2 amp in 3.2%, 5.4%, and 8.9% in intrahepatic chol-||||

|angiocarcinoma (iCCA), extrahepatic CCA, and gallbladder cancer. The most common co-GA||||

|included TP53, CDKN2A/B, and CCNE1. FGFR2 fusions (iCCA) were mutually exclusive with||||

|ERBB2 amp (0%, MDA/FMI); IDH1 (iCCA) with ERBB2 amp, 5.7 and 4.3% (MDA and FMI).||||

|Conclusions: Treatment outcomes and DNA co-GA occurring with ERBB2 amp.||||

|OS all patients||16.1 m||

|PFS, chemo 1 st line gem-based|4.2 vs. 4.1 m (p=0.70)|||

||vs. 5FU-based 2 nd line gem-based|3.0 vs 3.2 m (p=0.89)||

||vs. 5FU-based|||

|MDA (80)|Any co-amp(s) (72.7%), TP53 (70.4%), CDK12 amp (45.4%), CCNE1 amp (17.0%), CDKN2A/B|||

|DNA co-||(15.9%),||

|GA||KRAS (11.4%), ATM (11.2%), other ERBB2 GA (9.1%)||

|FMI DNA|iCCA (7,963)|||

|co-GA||6/2.5%)||

||eCCA (1,285) TP53 (85.3%), CDKN2A (37.3%), CDKN2B (21.3%), SMAD4 (20%), MTAP loss|||

|||(14.8%), KRAS mutation (14.7%), RBM10 (11.3%), and ERBB3 (10.7%)||

||Gallbladder (3,837) TP53 (89.6%), CDKN2A (30.4%), CCNE1 amp (21.4%), CDKN2B (19.1%),|||

|||SMAD4 (15%), CDK12 rearrangement (12.4%), MTAP loss (11.3%)||

|498|Poster Session| |---|---|

|sponse rate (ORR) by RECIST 1.1 (per investigator) and treatment-related adverse events (TRAEs)|||||||||| |---|---|---|---|---|---|---|---|---|---|

|per CTCAE v.5.0. Results: Between February and May 2023, 59 pts initiated treatment with STRIDE||||||||||

|or DUR (mean age 67.2 years, male sex 81.4%). 33 pts (55.9%) were treated in first-line (1L) and 26||||||||||

|(44.1%) in second-or further-line (.1L). STRIDE regimen was administered in 24 patients (40.7%): 6||||||||||

|pts in 1L, 18 pts in .1L. Child-Pugh class was A in 32 pts (54.2%), being more common in pts treated||||||||||

|with STRIDE than DUR (79.2% vs 37.1%, p=0.003). ECOG-PS was 0 in 35 pts (59.3%) and it was more||||||||||

|common in pts treated with STRIDE than DUR (79.2% vs 47.0%, p=0.015). Outcomes are reported in||||||||||

|Table. After a median follow-up of 3.2 months (95%CI 2.6-3.8), median OS was not reached and 6-||||||||||

|month OS rate was 59.4%. In pts treated with STRIDE, median OS was not reached and 6-month OS||||||||||

|rate was 95.8%, while median OS was 4.9 months (95%CI 3.2-4.9) for DUR. Median PFS was||||||||||

|2.5 months (95% CI 1.9-3.8) and ORR (evaluable in 43 pts, 72.9%) was 16.3% (95%CI 6.5-33.5%). Any||||||||||

|grade TRAEs and grade 3-4 TRAEs were 42.4% (95%CI 27.4-62.5) and 10.2% (95%CI 3.7-22.1%),||||||||||

|respectively. TRAEs requiring systemic corticosteroid therapy occurred in 3 pts (5.1%).||||||||||

|Conclusions: Overall|STRIDE|DUR|First-line (n=33, 55.9%) STRIDE DUR|Second-or further-lines (n=26, 44.1%) STRIDE DUR||||||

||(N=59)|(n=24, 40.7%)|(n=35, 59.3%)|(n=6)|(n=27)|(n=18)|(n=8)|||

|Median OS|NR|NR|4.9|NR|NR|NR|3.2|||

|(months, 95%CI)|||(3.2-4.9)||||(1.9-3.2)|||

|6-month OS|59.4|95.8|59.4|100|50.9|94.4|47.6|||

|(%,95%CI)||||||||||

|||||||||500|Poster Session|

|||||||||Pts received HAIC of modified FOLFOX (oxaliplatin, 85 mg/m 2 ; leucovorin, 400 mg/m 2 ; 5-|Pts received HAIC of modified FOLFOX (oxaliplatin, 85 mg/m 2 ; leucovorin, 400 mg/m 2 ; 5-|

|||||||||fluorouracil bolus, 400 mg/m 2 on day 1; 5-fluorouracil infusion, 2400 mg/m 2 for 46 h),|fluorouracil bolus, 400 mg/m 2 on day 1; 5-fluorouracil infusion, 2400 mg/m 2 for 46 h),|

|Enrolled patients would receive treatment with TACE (TACE was repeated on demand,|lenvatinib (8 or 12 mg once daily for body weight ,60 or $60 kg), and tislelizumab|lenvatinib (8 or 12 mg once daily for body weight ,60 or $60 kg), and tislelizumab||||||||

|but , 5 times) followed by sintilimab 200 mg every 3 weeks and fruquintinib (5 mg QD,|(200 mg every 3 weeks). HAIC was allowed to repeat on demands. Primary endpoint was|(200 mg every 3 weeks). HAIC was allowed to repeat on demands. Primary endpoint was||||||||

|2w on/1w off) until intolerable toxicity or disease progression. The primary endpoint was|objective response rate (ORR) per RECIST 1.1. Secondary endpoints included ORR per|objective response rate (ORR) per RECIST 1.1. Secondary endpoints included ORR per||||||||

|progression free survival (PFS). The secondary endpoints included adverse events (AEs),|mRECIST, disease control rate (DCR), surgical conversion rate, progression-free survival|mRECIST, disease control rate (DCR), surgical conversion rate, progression-free survival||||||||

|overall survival (OS), objective response rate (ORR) and disease control rate (DCR) per|(PFS), overall survival (OS), and adverse events (AEs). Results: Between June 2021 and|(PFS), overall survival (OS), and adverse events (AEs). Results: Between June 2021 and||||||||

|mRECIST. Results: As of August 20, 2023, 15 enrolled patients with uHCC were treated.|January 2023, 46 pts were enrolled. The median age of pts was 51-year-old, most were|January 2023, 46 pts were enrolled. The median age of pts was 51-year-old, most were||||||||

|Mean follow-up time is 10.7 months. The median age was 58 years. At present, 10|male 42 (91.3%), ECOG PS 0 33 (71.7%), C-P A 44 (95.7%), tumor diameter $10 cm 31|male 42 (91.3%), ECOG PS 0 33 (71.7%), C-P A 44 (95.7%), tumor diameter $10 cm 31||||||||

|patients were included for efficacy and safety analysis evaluation. Number of patients|(67.4%), multiple tumors 33 (71.7%), vascular invasion 38 (82.6%), extrahepatic me-|(67.4%), multiple tumors 33 (71.7%), vascular invasion 38 (82.6%), extrahepatic me-||||||||

|with CNLC stage Ⅱb and Ⅲa was 0 (0 %) and 15 (100 %), respectively. The median PFS|tastasis 7 (15.2%). As of August 15, 2023, . All pts entered efficacy and safety analysis,|tastasis 7 (15.2%). As of August 15, 2023, . All pts entered efficacy and safety analysis,||||||||

|and OS data are not yet mature. The ORR and DCR were 80% and 100% respectively|ORR was 52.2% (0 complete response [CR], 24 partial response [PR] ) per RECIST 1.1;|ORR was 52.2% (0 complete response [CR], 24 partial response [PR] ) per RECIST 1.1;||||||||

|based on mRECIST (1 CR, 10%; 7 PR, 70%; 2 SD, 20%). The most common ($ 10%)|ORR was 84.8% per mRECIST, with 5 CR and 34 PR. DCR was 95.6% per either RECIST 1.1|ORR was 84.8% per mRECIST, with 5 CR and 34 PR. DCR was 95.6% per either RECIST 1.1||||||||

|TRAEs ($ Grade 3) were elevated glutamic oxaloacetic transaminase, hypertension,|or mRECIST. Surgical conversion rate was 21.7% (10/46). Median PFS was 10.9 (95% CI,|or mRECIST. Surgical conversion rate was 21.7% (10/46). Median PFS was 10.9 (95% CI,||||||||

|proteinuria. No unexpected toxicity or treatment-related deaths occurred.|8.0-13.8) months; 12-month OS rate was 41.3%. COX analysis revealed that ECOG PS 1|8.0-13.8) months; 12-month OS rate was 41.3%. COX analysis revealed that ECOG PS 1||||||||

|Conclusions: Fruquintinib combined with sintilimab and TACE is a promising and|(HR, 3.17; 95% CI, 1.43-7.03; p=0.005), multiple tumors (HR, 3.68; 95% CI, 1.22-11.14;|(HR, 3.17; 95% CI, 1.43-7.03; p=0.005), multiple tumors (HR, 3.68; 95% CI, 1.22-11.14;||||||||

|tolerable therapeutic regimen for patients with CNLC Ⅱb-Ⅲa uHCC. This study is still|p=0.021), and extrahepatic metastasis (HR, 4.04; 95% CI, 1.57-10.40; p=0.004) were|p=0.021), and extrahepatic metastasis (HR, 4.04; 95% CI, 1.57-10.40; p=0.004) were||||||||

|ongoing and further follow-up is required to obtain final survival results. Clinical trial||||||||||

|information: NCT05971199. Research Sponsor: HUTCHMED Limited.||||||||||

|Median RFS was| |---|

|43.5m (95%CI, 27.5-59.6), while median overall survival was not reached (NR). mRFS|

|was significantly improved in pts with MPR (NR vs 28.3m [95%CI, 13.1-43.5], hazard ratio|

|[HR] 0.27 [95%CI, 0.11-0.69] , p = 0.003) and with pCR (NR vs 32.8m [95%CI, 15.2-50.4],|

|HR 0.20 [95%CI, 0.05-0.82], p=0.013). Conclusions:|

||Overall ITT|||||||||| |---|---|---|---|---|---|---|---|---|---|---|

||Population|ALBI Grade 1|ALBI Grade 2|CP Class A5|CP Class A6||||||

||Rivo +||Rivo +||Rivo +||Rivo +||Rivo +||

||Cam|Sora|Cam|Sora|Cam|Sora|Cam|Sora|Cam|Sora|

||n=272|n=271|n=200|n=206|n=72|n=63|n=236|n=230|n=36|n=41|

|mOS, mo|22.1 0.62 (0.49,0.80) a 0.62 (0.47, 0.83) 15.2 23.9 15.4 a|19.1 0.62 (0.4, 1.0) a 12.3|23.9 0.65 (0.5, 0.85) a 15.6|22.0 0.62 (0.35, 9.2 1.13) a|||||||

|mPFS, mo|5.6|3.7|6.1|3.7|5.6|3.1|6.1|3.7|4.4|3.1|

||0.52 (0.41, 0.65) a|0.57 (0.46, 0.73) a|0.57 (0.38, 0.86) a|0.58 (0.47, 0.72) a|0.53 (0.32, 0.91) a||||||

|DCR, % ORR b , %|78.3 25|53.9 6|78.0 35.5|56.7 9.1|79.2 26.4|54.0 12.7|80.1 33.1|56.5 10.4|66.7 33.3|53.7 7.3|

|Lifetime costs| |---|

|were highest with ATEZO-BEV ([£80,963 [95% CI: £11,022, £97,369]), followed by SOR-|

|REG (£38,373 [£31,064, £43,420]) and LEN (£37,351 [£5,020, £55,800] ). Quality-adjusted|

|life years (QALYs) were highest with ATEZO+BEV (1.021 [0.152, 1.239), followed by SOR-|

|REG (0.942 [0.802, 1.057]) and LEN (0.755, [0.094, 1.092] ). At a WTP threshold of|

|£30,000 / QALY gained, SOR-REG had an INMB of £40,211 (95% CI -£2,099, £52,731) and|

|£4,589 (-£8,044,|

|132s|HEPATOBILIARY CANCER||| |---|---|---|---|

|||eoCCA|aoCCA|

||Median Age (years)|44|68|

||Sex: Female|60.7%|54.6%|

||Sex: Male|39.3%|45.4%|

||Primary Tumor Site|||

||Intrahepatic|57%|53%|

||Extrahepatic|14%|16%|

||Gallbladder|21%|23%|

||Others|8%|8%|

||Homologous recombination deficiency was defined by pathogenic variant mutations (MT) in|||||| |---|---|---|---|---|---|---|

||ARID1A, ATM, ATR, BAP1, BRCA1, BRCA2, CDK12, CHEK2, FANC, NBN, PALB2, and RAD51.||||||

||Statistical analysis was performed using Chi-squared test for concurrent gene enrichment||||||

||and log-rank Kaplan-Meier analysis. Results: 483 CCA samples underwent tissue NGS as||||||

||standard of care. Pathogenic variants in HRD genes included ARID1A (15.5%, n=75), BAP1||||||

||(9.5%, n=46), ATM (2.7%, n=13), PALB2 (2.3%, n=11) and BRCA (2.0%, n=10), representing||||||

||31.7% (n=153) of the population. HRD mutations were found in similar proportions of lo-||||||

||calized (31.8%) and metastatic (31.5%) clinical presentations at diagnosis. OS was not||||||

||significantly different between CCA with HRD mutations (12.3 mo WT vs. 13.8 months with||||||

||HRD MT, p=64). HRD MT|HRD WT||HRD MT|HRD WT||

||KRAS WT|28.3% (137) 55.7% (269)|TP53 WT|22.8% (110) 30.8% (149)|||

||KRAS MT|3.3% (16) 12.6% (61)|TP53 MT|8.9% (43) 37.4% (181)|||

||% of HRD status|10.5%|18.5%|% of HRD status|28.1%|54.8%|

|547|Poster Session||||||

|Des-gamma-carboxy prothrombin (DCP) as a biomarker for treatment re-|||||||

|sponse in hepatocellular carcinoma. First Author: Elizabeth Conner, University of|||||||

|California, San Diego, San Diego, CA|||||||

|Results: Veterans diagnosed with CCA (07/2008-04/2023) underwent tissue-based NGS (n=483)| |---|

|including 96 unique VHA sites with male predominant population (96.9%). There was a predominance|

|of localized disease at clinical presentation (55.3%). A summary of common pathogenic variants is|

|provided (see table). Actionable alterations defined as IDH1mut, FGFR2fus, ERBB2amp, BRAFmut|

|(V600E), and MSI-H collectively represented 21.1% of all Veteran CCA. The largest population was|

|intrahepatic CCA (n=327) with actionable alterations including IDH1mut (13.5%), ERBB2amp (4.3%),|

|and FGFR2fus (4.3%). Data suggested improved overall survival (OS) in IDH1mut Intrahepatic CCA|

|including median OS 19.8 months (mo) v. 10.7 mo (p,0.03). ERBB2amp (n=32) was enriched in|

|extrahepatic (8.1%) and gallbladder cancer (17.2%), however did not improve OS including 7.1 mo in|

|ERBB2amp v. 13.2 mo in wildtype (p=0.15). PIK3CAmut CCA (n=35) was found to confer inferior OS|

|across the population with median OS of 7.5 mo v. 13.2 mo in wildtype (p,0.02). Additional pathologic|

|mutations in genes of homologous recombination deficiency (31.7%), PIK3CA (7.2%), and amplifi-|

|cations in MDM2 (5.0%). Conclusions:|

|Common alterations in CCA by primary location.||||| |---|---|---|---|---|

|||Hilar|Extrahepatic|Gallbladder|

||Intrahepatic (n=327)|(n=30)|(n=62)|(n=64)|

|IDH1mut|13.5%|6.7%|0|1.6%|

|ERBB2amp|4.3%|6.7%|8.1%|17.2%|

|FGFR2fus|4.3%|3.3%|0|0|

|BRAFmut (V600E)|1.2%|3.3%|0|0|

|TP53mut|37.9%|36.7%|69.4%|71.9%|

|KRASmut|12.5%|33.3%|40.3%|1.6%|

|PIK3CAmut|4.9%|13.3%|12.9%|10.9%|

|MDM2amp|2.8%|13.3%|6.5%|10.9%|

||DCA, 2006-2022) met inclusion criteria. Median survival was 29 months|DCA, 2006-2022) met inclusion criteria. Median survival was 29 months|DCA, 2006-2022) met inclusion criteria. Median survival was 29 months| |---|---|---|---|

|(IQR [25, 35]; 43 months [35, 48] resection, 17 months [13, 19] without). Compared to PCA, DCA was|(IQR [25, 35]; 43 months [35, 48] resection, 17 months [13, 19] without). Compared to PCA, DCA was|(IQR [25, 35]; 43 months [35, 48] resection, 17 months [13, 19] without). Compared to PCA, DCA was|(IQR [25, 35]; 43 months [35, 48] resection, 17 months [13, 19] without). Compared to PCA, DCA was|

|enriched in TP53mut (67 [69%] vs. 42 [33%] ), Q,0.01) and epigenetic pathway alterations (44 [45%] vs.|enriched in TP53mut (67 [69%] vs. 42 [33%] ), Q,0.01) and epigenetic pathway alterations (44 [45%] vs.|enriched in TP53mut (67 [69%] vs. 42 [33%] ), Q,0.01) and epigenetic pathway alterations (44 [45%] vs.|enriched in TP53mut (67 [69%] vs. 42 [33%] ), Q,0.01) and epigenetic pathway alterations (44 [45%] vs.|

|37 [29%], Q=0.041) and had more altered pathways (3 vs. 2, Q,0.01). KRASmut was similar between|37 [29%], Q=0.041) and had more altered pathways (3 vs. 2, Q,0.01). KRASmut was similar between|37 [29%], Q=0.041) and had more altered pathways (3 vs. 2, Q,0.01). KRASmut was similar between|37 [29%], Q=0.041) and had more altered pathways (3 vs. 2, Q,0.01). KRASmut was similar between|

|PCA (46 [36%]) and DCA (36 [37%] ); however, PCA was enriched in KRAS G12V (16 [13%] vs. 4 [4%] ) and|PCA (46 [36%]) and DCA (36 [37%] ); however, PCA was enriched in KRAS G12V (16 [13%] vs. 4 [4%] ) and|PCA (46 [36%]) and DCA (36 [37%] ); however, PCA was enriched in KRAS G12V (16 [13%] vs. 4 [4%] ) and|PCA (46 [36%]) and DCA (36 [37%] ); however, PCA was enriched in KRAS G12V (16 [13%] vs. 4 [4%] ) and|

|Q61H (11 [9%] vs. 3 [3%] , PHC|DHC|Q||

|TP53mut, n=109|42 (33%)|67 (69%)|< 0.01|

|KRASmut, n=82|46 (36%)|36 (37%)|0.9|

|CDKN2Amut, n=42|22 (17%)|20 (21%)|0.6|

|ARID1Amut, n=39|17 (13%)|22 (23%)|0.2|

|SMAD4mut, n=39|17 (13%)|22 (23%)|0.2|

|RTK-RAS, n=137|71 (56%)|66 (68%)|0.2|

|TP53, n=134|60 (47%)|74 (76%)|< 0.01|

|Epigenetic, n=81|37 (25%)|44 (45%)|0.04|

|Cell Cycle, n=66|32 (25%)|34 (35%)|0.2|

|TGF-B, n=52|26 (20%)|26 (27%)|0.4|

|First Author:| |---|

|Ankita Kapoor, Roswell Park Comprehensive Cancer Center, Buffalo, NY|

|||||564|Poster Session| |---|---|---|---|---|---|

|||||Epidemiological characteristics of patients with cholangiocarcinoma with|Epidemiological characteristics of patients with cholangiocarcinoma with|

|||||and without ulcerative colitis: A retrospective cohort study. First Author:|and without ulcerative colitis: A retrospective cohort study. First Author:|

|||||Alejandro Nieto Dominguez, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL|Alejandro Nieto Dominguez, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL|

|SEP and OS|Correlation Coefficient|95% CI|p|Number of Trials||

|1 st line||||||

|PFS|0.75|0.43 -0.90|, 0.001|18||

|TTP|0.67|0.15 -0.90|0.018|12||

|DORR|0.68|0.36 -0.86|, 0.001|12||

|Subsequent line||||||

|PFS|0.91|0.63 -0.98|, 0.001|9||

|TTP|0.89|0.50 -0.98|0.005|8||

|570 Intrahepatic cholangiocarcinoma: Recurrence patterns, genomics and Poster Session survival. Time to recurrence (TTR) and recurrence-free (RFS) were calculated from time of resection while OS was calculated from time of recurrence. Primary tumors underwent targeted next generation sequencing. Clinical, histopathologic and genomic factors associated with site(s) of recurrence, RFS and OS were assessed. Results: A total of 318 patients (n=296 MSK, n=22 EMC) treated between 1993 and 2021 met inclusion criteria and were analyzed; 232 patients (73%) developed recurrence. TTR was 11 (9.8, 12) months; OS and RFS was 26 (20, 33) and 14 (13, 18) months, respectively, among patients that recurred. Sites of first recurrence were LO 93 (40%), EH 80 (34%) and SIM 59 (26%). Median OS was similar in the LO (33 [26,42] months) and EH groups (33 [23,46] months) but much lower in SIM (12 [9.8,18] months) (p , 0.001). Moderate/poor tumor differentiation (p = 0.004), LVI (p = 0.004), N1 disease (p = 0.003), and PNI (p = 0.012) were associated with SIM; only positive resection margin predicted LO (p = 0.007). No individual genomic or pathway alterations predicted site of initial recurrence; however, for all patients, TP53mut (HR 2.01, 1.4-2.9; p , 0.001), CDKN2Adel (HR 1.96, 1.29-2.98; p = 0.003), CDKN2Bdel (HR 3.2, 2.03-5.05; p , 0.001) and KRASmut (HR 2.49, 1.56-3.96; p , 0.001) were as-sociated with worse survival. On multivariable analysis, SIM (HR 2.23, 1.49-3.34; p , 0.001), clinical stage III (HR 1.94, 1.26-2.99; p = 0.011), and alterations in TP53 (HR 2.07, 1.4-3.07; p , 0.001), CDKN2B (HR 4.1, 2.53-6.63; p , 0.001) and KRAS (HR 2.72, 1.68-4.43; p 571 Poster Session Lifestyle factors, viral hepatitis, and hepatocellular carcinoma in Uganda. First Author: Redeat Assefa, Johns Hopkins University, Baltimore, MD Background: The effect of lifestyle factors, namely alcohol use, cigarette smoking, and other forms of tobacco use on hepatocellular carcinoma (HCC) remains unclear. We assessed the independent associations of lifestyle factors with HCC among individuals with and without viral hepatitis. Methods: In a hospital-based case-control study recruiting from Mulago and Lacor hospitals in Uganda from March 2015 to August 2021, HCC cases were confirmed by clinical and ultrasound criteria, with biochemical and pathology confirmation on a subset. Controls were frequency matched by age and sex and from the same hospitals. Demographic, clinical and lifestyle data were collected using standardized instruments. Alcohol content of local drinks was standardized, and intensity categorized as light, moderate, or heavy based on CDC definitions. We analyzed alcohol (use status (current, former, never), duration (years), frequency (drinks/week)), cigarette smoking (status (current, former, never), cumulative (pack-years), duration (years), intensity (cigarettes/day), and time since cessation), other tobacco use (tobacco chewing and pipe-smoking), and viral hepatitis (HBV surface antigen (HBsAg) and HCV antibody (HCVAb)). We used logistic regression models (Stata 18.0) to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CIs) controlling for age, sex, family history of HCC, socioeconomic status, and Schistosomiasis (urine Circulating Cathodic Antigen (CCA)). Stratified analyses were performed separately by HBV and HCV status. Results: Among 596 HCC cases and 1,277 controls, the median age (IQR) was 43 (32-56) and 45 (31-54) years, 410 (68.8%) and 832 (65.0%) were males, 460 (24.6%) and 442 (23.7%) current or former alcohol users, 96 (5.1%) and 251 (13.4%) current or former cigarette smokers, and 177 (9.45%) and other tobacco users, respectively. Other tobacco users were more likely to be heavy (P10 pack-years) cigarette smokers (aOR=5.10; 95% CI: 2.41-10.79), heavy (.14 drinks/week for males and .7 drinks/week for females) alcohol drinkers (aOR=5.25; 95% CI: 2.84-9.68), farmers (aOR=1.61; 95% CI: 1.01-2.57) and lower socioeconomic status (aOR=3.23; 95% CI: 1.76-5.94). HCC risk was associated with HBV (aOR=18.66; 95% CI: 12.96-27.88), HCV (aOR= 4.03; 95% CI:2.31-7.02), and other tobacco use (aOR=1.86; 95%CI: 1.13-3.08). The observed HCC risk with other tobacco use, and the null associations with heavy alcohol use (aOR= 0.89; 95% CI: 0.60-1.31) and heavy cigarette smoking (aOR=0.74, 95% CI:0.34-1.60), were homogenous by HCV status (positive versus negative), and similarly by HBV status. Conclusions: TPS572 Trials in Progress Poster Session FOENIX-CCA4: A phase 2 study of futibatinib 20 mg and 16 mg in patients with advanced cholangiocarcinoma (CCA) and fibroblast growth factor re-ceptor 2 (FGFR2) fusions/rearrangements. First Author: Teresa Macarulla, Department of Medical Oncology, Vall d´Hebrón University Hospital, Vall d´Hebrón Institute of Oncology (VHIO), Barcelona, Spain Background: In 2022, the U.S. FDA approved futibatinib, a covalently binding inhibitor of FGFR1-4, for previously treated patients with advanced intrahepatic CCA and FGFR2 fusions/rearrangements. In the pivotal phase 2 FOENIX-CCA2 study, futibatinib 20 mg once daily (QD) resulted in an objective response rate (ORR) of 42% by independent review and a median duration of response (DOR) of 9.7 months. Futibatinib was tolerable and had a manageable safety profile. 1 Limited phase 1 data suggest futibatinib may also have antitumor activity at a lower dose (16 mg QD), with fewer dose modifications required for adverse events. 2 The aim of FOENIX-CCA4is to confirm the clinical benefit of futibatinib 20 mg QD and explore the safety and efficacy of futibatinib 16 mg QD in previously treated patients with advanced CCA and FGFR2 fusions/rearrangements. Methods: In this global, phase 2, randomized, open-label study (NCT05727176), pa-tients with CCA harboring FGFR2 fusions/rearrangements who have received $1 line of gemcitabine/platinum-based therapy for advanced/metastatic disease will be ran-domized 1:1 to futibatinib at a starting dose of 20 mg or 16 mg QD continuously on a 21-day cycle. Randomization will be stratified by the number of prior lines of systemic therapy for advanced disease (1 vs $2). Futibatinib will be continued until progressive disease or unacceptable toxicity. Tumor response will be assessed at baseline, every 6 weeks for the first 12 weeks, and every 9 weeks thereafter until radiographic pro-gressive disease or initiation of new anticancer therapy. The primary endpoint is ORR according to Response Evaluation Criteria in Solid Tumors version 1.1, as assessed by blinded independent central review (analyzed when all patients responding to futibatinib have $6 months' follow-up from the first onset of response). DOR is a key secondary endpoint. Glutamine antagonist DRP-104 in combination with durvalumab in patients with advanced fibrolamellar carcinoma (FLC) following progression on prior anti-PD(L)1 therapy. First Author: Mari Nakazawa, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD Trials in Progress Poster Session Sequential or up-front triple combination with durvalumab, tremelimumab, and bevacizumab for patients with unresectable hepatocellular carcinoma (HCC): MONTBLANC. First Author: Enrico N. De Toni, Klinikum der Universität Background: TPS574 München -Großhadern, CCC München, München, Germany| |---|

|TPS575 First-308: Phase III study of tinengotinib versus physician's choice in pa-Trials in Progress Poster Session tients with FGFR-altered, chemotherapy-and FGFR inhibitor-refractory/ relapsed cholangiocarcinoma. First Author: Milind M. Javle, Department of Gas-trointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX Background: Fibroblast growth factor (FGFR) alterations occur in 10-15% of adult patients with advanced intrahepatic cholangiocarcinoma (CCA) and 1-2% of adult patients with advanced extrahepatic cholangiocarcinoma. The first generation FGFR inhibitors (FGFRi) pemigatinib and futibatinib, have been approved for the treatment of advanced CCA with FGFR2 fusions or rearrangements after systemic chemotherapy. However, disease pro-gression occurs within 6-9 months. Secondary polyclonal mutations in the FGFR kinase domain represent a prominent acquired resistance mechanism. Tinengotinib, a novel multi-kinase inhibitor with high potency against a variety of FGFR2 kinase domain mutations, has shown promising clinical benefit in subjects with FGFR-altered metastatic CCA who were heavily pretreated with chemotherapy and FGFRi(s) in phase I/II clinical trials. (NCT03654547, NCT04742959, NCT04919642). Methods: FIRST-308 is a phase III, ran-domized, global multicenter study to evaluate the efficacy and safety of oral tinengotinib versus Physician's Choice in subjects with FGFR-altered, chemotherapy-and FGFRi-refractory/relapsed CCA. Approximately 200 subjects will be enrolled in US, Europe, and Asia. Key eligibility criteria include age $ 18 years, ECOG performance status 0 or 1, documentation of FGFR2 fusion/rearrangement gene status, prior treatment with at least one line of chemotherapy and exactly one prior FDA-approved FGFRi for unresectable or metastatic disease. The study includes Part A and Part B. The Part A is to select a dose for Part B. Eligible subjects will be randomized in a 2:2:1 ratio to receive tinengotinib 8 mg QD, tinengotinib 10 mg QD or Physician's Choice (FOLFOX or FOLFIRI) in Part A or 2:1 in Part B to receive the recommended Part B dose or Physician's Choice. The stratification factors at randomization include geographic region, prior lines of chemotherapy (1 or $ 2) and Physician's choice. TPS576 An open-label, multicenter study investigating RP3 oncolytic immunother-Trials in Progress Poster Session apy in combination with first-or second-line systemic atezolizumab plus bevacizumab in patients with locally advanced unresectable or metastatic hepatocellular carcinoma. First Author: Kevin Kim, University of Maryland School of Medicine, Baltimore, MD Background: Despite advances in treatment for unresectable hepatocellular carcinoma (HCC), long-term survival rates remain poor. The combination of atezolizumab (Atezo) plus bevacizumab (Bev) is approved frontline therapy for advanced HCC, but a minority of patients (pts) respond and secondary resistance usually occurs within months. HCC has an immune-suppressed tumor microenvironment (TME), mediated by activated immune checkpoint signaling and angiogenesis pathways, which may contribute to therapeutic resistance. RP3 is a genetically modified herpes simplex virus type 1 (HSV-1) that ex-presses the fusogenic gibbon ape leukemia virus glycoprotein with the R sequence deleted (GALV-GP-R-), an anti-CTLA-4 antibody-like molecule, CD40 ligand, and 4-1BB ligand. The direct oncolytic effect coupled with immune stimulation by RP3 in the TME is intended to provide systemic antitumor activity and synergize with anti-PD-1/PD-L1 agents, such as Atezo. Preclinical data have demonstrated improved distribution of oncolytic HSV within tumors in combination with Bev, supporting the clinical combination of RP3 with Bev. This study will evaluate the safety and efficacy of RP3 combined with Atezo plus Bev as first-(1L) and second-line (2L) systemic therapies for unresectable and advanced HCC (NCT05733598). Methods: The 1L and 2L cohorts will each enroll up to 30 pts. Pts in the 1L cohort may not have received prior systemic treatment; pts in the 2L cohort must have progressed on or following 1 prior line of systemic therapy, which must have included a PD-1/PD-L1-directed agent. Key inclusion criteria include advanced unresectable HCC with $1 measurable tumor of $1 cm in longest diameter, Child-Pugh class A, and an Eastern Cooperative Oncology Group performance status of 0 to 1. Key exclusion criteria include untreated esophageal and/or gastric varices with bleeding or at high risk for bleeding and macroscopic invasion of the tumor into any major blood vessel(s) and/or main bile ducts. Pts with a history of medically refractory hepatic encephalopathy and/or hepato-renal syndrome are also excluded. Pts in the 1L cohort will receive Atezo 1200 mg and Bev 15 mg/kg every 3 weeks (Q3W) together with RP3 intratumorally Q3W for a total of up to 8 doses. Pts in the 2L cohort will receive RP3 every 2 weeks for 4 doses with Bev Q3W starting on cycle (C)1 day (D)1, then RP3 and Bev Q3W for up to 4 more doses with Atezo Q3W being added on C4D1. observed in up to 95% of HCC cases. TTI-101 is a first-in-class, orally delivered, small molecule, direct inhibitor of STAT3 activation. TTI-101 monotherapy demonstrated tumor growth arrest as well as reversal of liver injury and fibrosis in a genetically modified mouse model (HepPten -) which recapitulates the pathogenesis of HCC in non-alcoholic fatty liver disease (NAFLD), as well as in combination with immune checkpoint inhibition in a humanized HCC mouse model. 1,2 TTI-101 monotherapy was found to be well tolerated in a Phase 1 trial conducted in patients (pts) with advanced solid tumors (NCT03195699). Of 15 evaluable HCC pts, 60% demonstrated clinical benefit, including 20% confirmed partial responses (median duration=10.5 months). All pts were relapsed/ refractory to standard of care (SOC; median prior systemic therapy=2), including anti-PD-(L)1 based therapy. TPS578 Trials in Progress Poster Session| |---|

||TPS582|Trials in Progress Poster Session| |---|---|---|

||geting VEGFR1/2/3, FGFR1-4 and PDGFRa/b, which effectively blocks tumor neo-|geting VEGFR1/2/3, FGFR1-4 and PDGFRa/b, which effectively blocks tumor neo-|

||vascularization and growth. Previous phase I/II clinical trials suggested that anlotinib|vascularization and growth. Previous phase I/II clinical trials suggested that anlotinib|

||combined with PD-(L)1 inhibitors as second-line therapy was well tolerated and showed|combined with PD-(L)1 inhibitors as second-line therapy was well tolerated and showed|

||clinical anti-tumor activity in advanced biliary tract cancer (NCT03825705,|clinical anti-tumor activity in advanced biliary tract cancer (NCT03825705,|

||NCT03996408, ChiCTR1900022003, ChiCTR2000037847). Penpulimab is a novel hu-|NCT03996408, ChiCTR1900022003, ChiCTR2000037847). Penpulimab is a novel hu-|

||manized anti-PD-1 IgG1 antibody with complete removal of Fc receptor mediated effect,|manized anti-PD-1 IgG1 antibody with complete removal of Fc receptor mediated effect,|

||and featuring slow antigen binding off-rate and high receptor occupancy. In this study,|and featuring slow antigen binding off-rate and high receptor occupancy. In this study,|

||we explore anlotinib plus penpulimab as a chemo-free combination for second-line and|we explore anlotinib plus penpulimab as a chemo-free combination for second-line and|

||above therapy. Methods: This is a prospective, single-arm, phase II study. BTC patients|above therapy. Methods: This is a prospective, single-arm, phase II study. BTC patients|

||(pts) failed after the first-line treatment, aged 18-75 and an ECOG PS of 0-1 were|(pts) failed after the first-line treatment, aged 18-75 and an ECOG PS of 0-1 were|

||recruited.Eligible pts received anlotinib (12mg, po, d1-14, q3w) and penpulimab (200mg,|recruited.Eligible pts received anlotinib (12mg, po, d1-14, q3w) and penpulimab (200mg,|

||iv, d1, q3w) until disease progression, unacceptable toxicity or up to 2 years. The primary|iv, d1, q3w) until disease progression, unacceptable toxicity or up to 2 years. The primary|

||endpoint was Objective Response Rate (ORR). Secondary endpoints included Overall|endpoint was Objective Response Rate (ORR). Secondary endpoints included Overall|

||survival (OS), Progression-Free Survival (PFS), Disease Control Rate (DCR) and safety.|survival (OS), Progression-Free Survival (PFS), Disease Control Rate (DCR) and safety.|

||Based on a two-sided test for one proportion with 5.0% type I error, 80% power to detect|Based on a two-sided test for one proportion with 5.0% type I error, 80% power to detect|

||an improvement in ORR from 5% to 22%, there will be 27 pts enrolled considering 20% of|an improvement in ORR from 5% to 22%, there will be 27 pts enrolled considering 20% of|

||pts dropping out. Clinical trial information: ChiCTR2300069126. Research Sponsor:|pts dropping out. Clinical trial information: ChiCTR2300069126. Research Sponsor:|

||None.||

|TPS583|Trials in Progress Poster Session||

|ADJUBIL: A phase II study of immunotherapy with durvalumab and trem-|||

|elimumab in combination with capecitabine or without capecitabine in|||

|adjuvant situation for biliary tract cancer. First Author: Thorsten Goetze,|||

|Institute of Clinical Cancer Research (IKF) at Krankenhaus Nordwest, UCT-University|||

|Cancer Center and Frankfurter Institut für Klinische Krebsforschung IKF GmbH at|||

|Krankenhaus Nordwest, Frankfurt Am Main, Germany|||

|||Clinical trial information:|

||NCT05937295. Research Sponsor: Else Kröner Fresenius Foundation (Grant 2022_EKTP03|NCT05937295. Research Sponsor: Else Kröner Fresenius Foundation (Grant 2022_EKTP03|

||(J.S.W.)); Medical Faculty of Eberhard Karls University Tübingen, Germany E.03.28048.2;|(J.S.W.)); Medical Faculty of Eberhard Karls University Tübingen, Germany E.03.28048.2;|

||Roche Pharma AG.||

|TPS586|Trials in Progress Poster Session| |---|---|

|and surveillance. Interleukin-12 (IL-12) is a pro-inflammatory cytokine with extensive|and surveillance. Interleukin-12 (IL-12) is a pro-inflammatory cytokine with extensive|

|anti-tumor properties, but therapeutic development of recombinant human IL-12 (rhIL-|anti-tumor properties, but therapeutic development of recombinant human IL-12 (rhIL-|

|12) was halted due to significant systemic toxicities. PDS0301 (formerly M9241) is a|12) was halted due to significant systemic toxicities. PDS0301 (formerly M9241) is a|

|novel human monoclonal antibody (NHS76) fused to two IL-12 heterodimers. The NHS76|novel human monoclonal antibody (NHS76) fused to two IL-12 heterodimers. The NHS76|

|antibody specifically targets histone/DNA complexes in regions of cellular necrosis|antibody specifically targets histone/DNA complexes in regions of cellular necrosis|

|resulting in accumulation within tumors. Importantly, recent Phase I trials have shown|resulting in accumulation within tumors. Importantly, recent Phase I trials have shown|

|PDS0301 monotherapy to be well tolerated. We hypothesize that synchronization of|PDS0301 monotherapy to be well tolerated. We hypothesize that synchronization of|

|PDS0301 administration with tumor cell death induced by locoregional and systemic|PDS0301 administration with tumor cell death induced by locoregional and systemic|

|chemotherapies will demonstrate increased efficacy over standard of care therapy.|chemotherapies will demonstrate increased efficacy over standard of care therapy.|

|Methods: This is a single center, non-randomized Phase II study to determine the safety|Methods: This is a single center, non-randomized Phase II study to determine the safety|

|and efficacy of PDS0301 in combination with floxuridine (FUDR) administered by hepatic|and efficacy of PDS0301 in combination with floxuridine (FUDR) administered by hepatic|

|artery infusion pump (HAIP) and systemic chemotherapies in patients with either|artery infusion pump (HAIP) and systemic chemotherapies in patients with either|

|unresectable metastatic colorectal cancer (mCRC) or intrahepatic cholangiocarcinoma|unresectable metastatic colorectal cancer (mCRC) or intrahepatic cholangiocarcinoma|

|(ICC). Eligibility criteria include histologically or cytologically confirmed colorectal|(ICC). Eligibility criteria include histologically or cytologically confirmed colorectal|

|adenocarcinoma metastatic to the liver (Cohort 1) or unresectable intrahepatic chol-|adenocarcinoma metastatic to the liver (Cohort 1) or unresectable intrahepatic chol-|

|angiocarcinoma with no evidence of extrahepatic metastases (Cohort 2). Patients will|angiocarcinoma with no evidence of extrahepatic metastases (Cohort 2). Patients will|

|receive HAIP-administered (FUDR) plus PDS0301 at a starting dose of 12mcg/kg in 28-|receive HAIP-administered (FUDR) plus PDS0301 at a starting dose of 12mcg/kg in 28-|

|day cycles. Beginning in cycle 2, systemic chemotherapy with FOLFOX (Leucovorin, 5-|day cycles. Beginning in cycle 2, systemic chemotherapy with FOLFOX (Leucovorin, 5-|

|Fluorouracil [5-FU], and Oxaliplatin) or FOLFIRI (Leucovorin, 5-FU and Irinotecan) for|Fluorouracil [5-FU], and Oxaliplatin) or FOLFIRI (Leucovorin, 5-FU and Irinotecan) for|

|Inclusion criteria includes patients over 18 years old with an ECOG PS of 0 or 1, no cirrhosis or Child-Pugh A cirrhosis, diagnosis of HCC by imaging or biopsy, and EGD within 6 months with no evidence of gastroesophageal varices with bleeding or high risk of bleeding unless treated. Patients are excluded if they are candidates for curative intent therapy, have had hepatic encephalopathy in the last 12 months, have occlusion of the hepatic artery or main portal vein, or have history of significant autoimmune disease. 1. Finn, Richard S., et al. New England Journal of Medicine 382.20 (2020): 1894-1905. 2 Lee J and Liu D. Clinical Trials. 2008; 5(2): 93-106. Clinical trial information: NCT05776875. Research Sponsor: Genentech. mCRC or GemOx (TPS587 Trials in Progress Poster Session A phase 2/3 randomized study of CTX-009 combination in 2L biliary tract cancer: COMPANION-002. First Author: Olivia Aranha, Washington University School of Medicine in St. Louis, St. Louis, MO Background: Biliary tract cancer (BTC) is characterized by generally poor prognoses with limited treatment options. Systemic chemotherapy usually begins with gemcita-bine, platinum agents, and a checkpoint inhibitor followed by 5-FU and oxaliplatin, irinotecan or a taxane. Presently, there is no consensus second-line therapy for patients with BTC. The DLL/Notch signaling pathway has been described to be a major driver of cholangiocarcinogenesis and VEGF-A overexpression has been reported in BTC tumors, correlating with stage, metastasis, and prognosis of the disease. CTX-009 is a recombinant bispecific antibody that binds both delta-like ligand-4 (DLL4) and vascular endothelial growth factor A (VEGF-A). The antibody simultaneously inhibits the DLL4-Notch 1 and VEGF A-VEGF receptor signaling pathways. Methods: COMPANION-002 (CTX-009 -002) is an open-label, randomized, controlled study in patients in second line advanced or metastatic BTC. To be eligible, patients must have radiologically docu-mented progression after a prior gemcitabine and platinum containing chemotherapy regimen as first line therapy for locally advanced unresectable or metastatic disease. 150 patients will be randomized in a 2:1 ratio to receive either CTX-009 plus paclitaxel or paclitaxel alone. The stratification factors to be used at randomization include stage (locally advanced vs. metastatic), anatomic subsite of primary tumor (intrahepatic cholangiocarcinoma vs. other, i.e. extrahepatic cholangiocarcinoma, gallbladder, or ampullary), and Eastern Cooperative Oncology Group (ECOG) Performance status (0 vs. 1). Patients will be treated in 28-day cycles, with CTX-009 administered at 10 mg/kg IV on Day 1 and 15, and paclitaxel administered at 80 mg/m2 on days 1, 8, and 15. The patients randomized to paclitaxel arm can crossover after disease progression if se-lection criteria continue to be met. The primary objective of the study is to assess the efficacy of CTX-009 in combination with paclitaxel vs. paclitaxel alone, as measured by Overall Response Rate (ORR) assessed by an Independent Central Radiology (ICR) review. Key secondary objectives include overall survival, progression-free survival, and duration of response. Clinical trial information: 251040. Research Sponsor: None. 590 Poster Session Repeat peptide receptor radionuclide therapy in neuroendocrine neoplasms: A NET Center of Excellence experience. First Author: Udhayvir Singh Grewal, University of Iowa Hospitals and Clinics, Iowa City, IA Background: Lu177 DOTATATE Peptide Receptor Radionucleotide Therapy (PRRT) was FDA approved in the United States in 2018 however this treatment modality has been widely available in European nations since early 2000s. Therefore, the data for the safety and efficacy of repeat PRRT are almost exclusively from European centers. We present a real-world experience with repeat PRRT in a cohort of US patients. Methods: We used our single-center longitudinal IRB approved neuroendocrine tumor (NET) registry to identify patients who had been previously treated with at least 1 dose of PRRT (PRRT 1, either Lu 177 DOTATATE or Y90 DOTATOC) and following disease progression were retreated with a second course of PRRT (PRRT 2). Patients who received alpha PRRT were not included. We reviewed patient, tumor and treatment characteristics, time to progression after PRRT 1 and PRRT 2 and toxicity. Results: A total of 153 patients received at least 1 dose of Lu-177 DOTATATE PRRT at our institution post FDA approval, out of which, 13/153 (8.5%) patients received repeat PRRT .2/13 patients were excluded due to lack of adequate follow up. All patients included were white (11/11, 100%). Median age of the participants was 65 years (IQR 63, 67) and 54.5% (6/11) patients were females. Most patients had grade 2 (9/11,81.8%) followed by grade 1 NET (2/11, 18.2%) and all except one patient included had a gastroenteropancreatic origin NET (10,11, 90.9%). 45.5% (5/11) patients received Lu-177 DOTATATE PRRT only both for PRRT1 and PRRT 2, while 54.5% (6/11) patients received Y90 DOTATOC PRRT for PRRT1. Median number of lines therapies before PRRT1 and PRRT were 2 (IQR 2,5) and 1 (IQR 1,2) respectively. Patients received a median of 3 (IQR 2, 4) and 3 (IQR 1,4) cycles for PRRT1 and PRRT2 respectively. At first restaging scan after PRRT1 (3-6 months), 54.5% and 45.5% patients had partial response (PR) and stable disease (SD) respectively. At first restaging scan after PRRT2 (3-6 months), 45.5%, 27.3% and 9.1% patients had SD, progressive disease (PD) and PR respectively; 2/11 patients (18.2%) died before first restaging scan. Median PFS for PRRT1 (n=11) was 22.5 months (IQR 12.7, 30.7). Median PFS (n=5) for PRRT2 was 10.9 months (IQR 10.05, 25.7). PFS was not reached for 1 patient after PRRT2. 1 (9.1%) patient each developed grade 2 nephrotoxicity and grade 3 Poster Session Quality of surveillance in patients with completely resected gastroentero-pancreatic neuroendocrine tumors. First Author: Gordon Taylor Moffat, Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, thrombocytopenia after PRRT2. Conclusions: 591 University Health Network, University of Toronto, Toronto, ON, Canada||

|146s|NEUROENDOCRINE/CARCINOID|| |---|---|---|

|Correlation Bulk transcriptional profiling was performed using the Nanostring PanCancer-Immune|||

|Panel. DSP was performed with whole human transcriptome using PanCK to segment|||

|tumor and adjacent stroma; 88 distinct regions were analyzed using differential gene|||

|expression and Reactome pathway enrichment pipelines. Results: Resected SBNETs|||

|from 42 patients were selected for transcriptional analysis. Unsupervised clustering of|||

|gene expression demonstrated dichotomization into high and low cancer testis antigen|||

|(CTA) expression. CTA-high patients (n=12) demonstrated elevated expression of type-I|||

|interferons (IFN) and CTAs such as PRAME, GAGE1, and MAGEA3 and had significantly|||

|longer OS compared to CTA-low patients (n=30; median OS not reached vs 1975 days,|||

|p=0.008). MVA controlling for age, sex, metastatic disease, and Ki-67% confirmed CTA-|||

|high status as an independent predictor of longer OS (hazard ratio [HR] 0.2, 95%|||

|confidence interval [CI] 0.05-0.83). A pilot DSP experiment with 4 CTA-high and 4 CTA-|||

|low tumors revealed higher expression of epigenetic modification genes (e.g., H3C1,|||

|H2BC8, p,0.001) in CTA-high tumors with significant enrichment in epigenetic|||

|pathways (e.g., histone acetylation, DNA methylation). CTA-high tumors exhibited in-|||

|creased M2 macrophage presence (p=0.025) and increased stromal compartment NK|||

|cell activation (p=0.001). Conclusions:|||

||Number of unnecessary surveillance investigations ordered for 87 patients on surveillance between|Number of unnecessary surveillance investigations ordered for 87 patients on surveillance between|

||2019-2022.||

||Test|Total Amount|

||CT Chest|111|

||CT Abdomen|40|

||CT Pelvis|119|

||MRI Abdomen|14|

||MRI Pelvis|9|

||US Abdomen|6|

||Gallium-68-DOTATATE PET Scan|2|

||Chromogranin A|33|

||24-HR Urine 5-HIAA|7|

||Extended Hormonal Testing|41|

||Flexible Sigmoidoscopy|3|

||Colonoscopy|7|

|Characteristics by tumor type, associations with distant metastasis at initial diagnosis, and DSS were determined using standard statistical methods. Results: Of 246 patients, 164 (66.7%) had type 1, 5 (2.0%) had type 2, 52 (21.1%) had type 3, 18 (7.3%) were PPI-associated, and 7 (2.8%) remained unclassified. Multifocal disease was more common for types 1 (56.1%) and 2 (40.0%) than type 3 (13.5%) and PPI-associated tumors (27.8%, P,0.001). Patients with type 3 GNET were also less likely to have WHO grade 1 tumors (26.9%) compared to other GNETs (type 1 37.2%, type 2 40.0%, PPI-associated 50.0%, P,0.001). Additionally, distant metastases at presentation oc-curred more frequently with type 3 (38.5%) than type 1 (1.2%), type 2 (20.0%), and PPI-associated tumors (11.1%, P,0.001). GNET type (type 1 vs 3, odds ratio [OR] 0.005 [95% confidence interval [CI] 0.001-0.050; PPI-associated vs type 3, OR 0.040 [95% CI 0.004-0.45]), race (non-white vs white, OR 0.17 [95% CI 0.040-0.73] ), and WHO grade (2/3 vs 1, OR 10.5 [95% CI 1.93-57.2]) were associated with distant metastasis at presentation. Five-year DSS rates were 100.0% for type 1, 59.7% (95% CI 42.7-73.2%) for type 3, and 90.9% (95% CI 50.8-98.7%) for PPI-associated (log-rank P,0.001). By multivariable analysis, multi-focality of primary tumors (hazard ratio [HR] 0.070 [95% CI 0.010-0.46]) and distant metastasis at diagnosis (HR 44.9, 95% CI 6.21-324.8) were independently associated with DSS, while tumor type was not (type 1 vs 3, HR 0.18 [95% CI 0.010-2.44); PPI-associated vs type 3, HR 0.13 [95% CI 0.010-1.33] ). Conclusions: PPI-associated tumors may represent a distinct GNET type with intermediate outcomes compared to type 1 and type 3 tumors. However, factors other than tumor type must be considered in determining survival. Research Sponsor: None. 599 Poster Session Potential biomarkers for treatment response in advanced non-pancreatic neuroendocrine tumors. First Author: Sahithi Sonti, Roswell Park Comprehensive Cancer Center, Buffalo, NY Background: Well-differentiated NETs are highly vascular and hence, inhibition of angiogenesis is of interest. VEGF, a key molecule in promoting angiogenesis, has also been shown to promote an immunosuppressive tumor microenvironment. Nintedanib, an oral inhibitor of FGFR1-3, VEGFR1-3 and PDGFRA, has previously been evaluated in a phase II clinical trial in well-differentiated, non-pancreatic NETs, where 83% of the evaluable patients were progression-free at 16 weeks and median PFS was 11 months. In preclinical studies, nintedanib has been shown to increase PD-L1 expression in tumor cells, which then results in improved outcomes with immune checkpoint inhibition. There are multiple indicators of T-cell exhaustion, including PD-L1 and LAG-3. LAG-3+ T-cells have been found to correlate with poor response to treatment in neuroendocrine neoplasms. Given these findings, this study evaluates serum VEGF and LAG-3 ex-pression to determine potential biomarkers of response in patients treated with nin-tedanib. Methods: 27 sets of paired samples collected at baseline and 8-weeks post treatment with nintedanib, from clinical trial NCT02399215 were used for this study. With IRB approval, we tested for serum VEGFa and serum LAG-3 using Luminex test kits: HCKP1-11K-01 (LAG-3) and HCYTA-60K-01 (VEGFa). We compared the baseline, 8-week, and percentage change in serum VEGF and serum LAG-3 levels with Rd Cd8+ pAkt+ T-cells (activated cytotoxic T-cells) as a marker of immune activation, Rd CD25+ pAkt+ T-cells (regulatory T-cells) as a marker of immune suppression, and PFS. Results: The median VEGF levels at baseline and 8-weeks were 10.50 pg/mL and 11.90 pg/mL respectively. The median LAG-3 level at baseline and 8-weeks were 59000 pg/mL and 62900 pg/mL respectively. Higher VEGFa levels in the post-treatment samples were associated with poorer progression free survival (HR= 1.009, 95% HR CI: [0.999, 1.019], with P= 0.0760). Higher levels of VEGF at baseline were also associated with lower numbers of Rd CD8+ pAkt + cells (Pearson coefficient = -0.42, p-value 0.04) at baseline. Increased baseline CD25+ pAkt+ levels were positively correlated with percent change in serum LAG-3 levels between baseline and post-treatment samples. (Pearson Co-efficient: 0.45; p=value: 0.02). Conclusions: highest risk of malignancy of the rectum (O/E: 6.4, CI: 7.26 -5.21, N= 239) and this 598 Poster Session Prognostic value of O 6 -methylguanine-DNA methyltransferase (MGMT) status in pancreatic neuroendrocrine tumors with capecitabine and temo-zolomide (CAPTEM). First Author: Eduardo Terán Brage, Hospital Universitario de Salamanca, Salamanca, Spain Background: Loss of MGMT expression has been suggested as a predictor of response to alkylating agents in pancreatic neuroendocrine tumors (pNET), however, its determination is controversial. We aim to analyze the prognostic value of MGMT status assessed by im-munohistochemistry (IHC) or pyrosequencing (PSQ) in patients with pNET receiving CAPTEM. Methods: Retrospective and unicentric analysis in patients (p) with pNET treated with CAPTEM from April 2008 to February 2023. MGMTdeficiency was determined by IHC and MGMT promoter methylation by PSQ. We analyzed patients' characteristics, progression-free survival (PFS) and overall survival (OS) according to MGMT status. Results: 20p were included. Age (medi an): 62 [46-77]. Males (45%). Tumor grade (G): G1 (15%), G2 (55%) and G3 (20%). MGMT deficiency was detected in 12p (60%) and promoter methylation in 10p (50%). Results by IHC were consistent with PSQ in 10p (50%), with mismatches in 4p (methylated MGMT and positive IHC) and 6p (unmethylated MGMT and negative IHC). We reported a higher response rate in MGMT-deficient and MGMT-methylated p (Table). In MGMT-deficient p we observed significantly better PFS (88m vs 11.1m; p=0.02, HR=0.21) and OS (141.9m vs 35.8m; p=0.03, HR=0.20). Also, in MGMT-methylated p we detected better PFS (88m vs 17.7m; p=0.20, HR=0.44) and OS (188.7m vs 141.9m; p=0.11, HR=0.28). A subanalysis was performed based on G, showing better PFS (88m vs 6.2m; p=0.03, HR=0.11) and OS (188.7m vs 35.8m; p,0.01, HR=0.06) in those with G2 vs G3. There was a strong negative correlation between G and MGMT by PSQ; the higher G, the lower probability of promoter methylation r(16)= -0.62, p,0.01. Conclusions: Our results support MGMT status, deficiency by IHC or promoter methylation by PSQ, as a potential prognostic biomarker in pNET treated with alkylating agents. However, it is necessary to evaluate its prognostic value in prospective studies. Research Sponsor: None. Response rate according to MGMT status assessed by immunohistochemistry (IHC) and pyrosequencing (PSQ). MGMT (IHC) MGMT (PSQ) 1-2 (Low) 3 (High) Negative Positive increased risk of rectal cancer persists even 10 years after the initial diagnosis (0/E: 3.8, CI: 5.37-2.6, N= 32). There is no increased risk of cancer of the colon excluding rectum (O/E: 0.98, CI: 1.18-0.81, N= 114). Even after 10 years from diagnosis there is increased risk of recurrence of the NET of the Colon (O/E: 1.28, CI: 1.55-1.06, N=110) and NET of the Rectum (O/E: 1.12, CI: 1.23-1.02, N= 433). There is also increased incidence of small intestine cancer (O/E: 2.92, CI: 4.17-1.97, N=30), Prostate cancer (O/E: 1.28, CI: 1.41-1.15, N=400), Kidney and renal pelvis cancer (O/E: 1.53, CI: 1.86 -1.25, N= 104), Thyroid cancer (O/E: 1.63, CI: 2.12-1.23, N= 55) and Nodal Non-Hodgkins Lymphoma (O/E: 1.34, CI: 1.71-1.03, N=64). Conclusions: TPS601 Trials in Progress Poster Session||||||| |---|---|---|---|---|---|---|

|Response|||Total|||Total|

|Yes|8 (66,7%)|4 (50%)|12 (60%)|4 (40%)|8 (80%)|12 (60%)|

|No|4 (33,3%)|4 (50%)|8 (40%)|6 (60%)|2 (20%)|8 (40%)|

|Total|12 (100%) 8 (100%) 20 (100%) 10 (100%) 10 (100%) 20 (100%)||||||

||OR [95% CI] of 2,0 [0,32-12,5]|OR [95% CI] of 2,0 [0,32-12,5]|OR [95% CI] of 2,0 [0,32-12,5]|OR [95% CI] of 2,0 [0,32-12,5]|OR [95% CI] of 6,0 [0,81-44,31]|OR [95% CI] of 6,0 [0,81-44,31]|

|||(p=0,64)|||(p=0,17)||

|Here we report the preliminary efficacy and safety results of glecirasib in pts with PDAC| |---|

|and other solid tumors (excluding NSCLC and CRC) from the pooled population of both|

|trials. Results: As of Sep 8, 2023, a total of 48 pts have received glecirasib monotherapy|

|(41 from NCT05009329 and 7 from NCT05002270) and 47 were evaluable for efficacy. This|

|includes 28 PDAC and 19 other solid tumors (7 biliary tract, 3 gastric, 3 small bowel, 1|

|appendiceal, 1 hepatocellular, 1 peritoneal, 1 posterior bronchial mediastinal, 1 amelo-|

|blastic carcinoma and 1 cervical). At baseline, pts had previously received a median of one|

|line of systemic therapy (range: 0 to 4; with 23 pts have received one prior line); 85% Asian,|

|15% Caucasian; most (45 pts) at 800 mg QD. Among 28 pts with PDAC, 13 achieved|

|confirmed partial response (PR) with the confirmed objective response rate (ORR) of 46.4%|

|(13/28) and disease control rate (DCR) of 96.4%; the median duration of response (DOR)|

|and progression-free survival (PFS) were 4.1 months and 5.5 months (95%CI 1.2, 13.1),|

|respectively. Among 19 pts with other tumor types, the confirmed ORR of 52.6% (10/19)|

|and DCR of 84.2% (16/19) were observed; the median DOR and PFS were 8.3 months and|

|7.0 months (95% CI 1.1 to 15.2), respectively. Treatment-related AE (TRAE) of any grade|

|occurred in 89.6% (43/48) pts; the most common ($10%) TRAE were anemia (52.1%),|

|blood bilirubin increased (39.6%), white blood cell count decreased (18.8%), AST increased|

|(18.8%), diarrhea (16.7%), ALT increased (14.6%), asthenia (14.6%), hypertriglyceridemia|

|(10.4%), and nausea (10.4%); $Grade 3 TRAE occurred in 25% (12/48) pts; no TRAE were|

|fatal or led to treatment discontinuation. Conclusions: Glecirasib monotherapy is well|

|tolerated and has a manageable safety profile and exhibits promising anti-tumor activity in|

|pts with KRAS G12C mutated PDAC and other solid tumors. Further clinical development of|

|glecirasib in above mentioned population is ongoing (NCT06008288). Clinical trial in-|

|formation: NCT05009329 and NCT05002270. Research Sponsor: Jacobio Pharmaceuticals|

|Co., Ltd.|

|605 Alternating application of gemcitabine/nab-paclitaxel (Gem/nab-Pac) and Rapid Oral Abstract Session Gem monotherapy or continuous application of Gem/nab-Pac after induc-tion treatment for first-line treatment of metastatic pancreatic cancer (mPC): First results from the randomized phase 2 ALPACA study from the German AIO study group (AIO-PAK-0114). First Author: Klara Dorman, Department of Medicine III and Comprehensive Cancer Center, University Hospital, LMU Munich and German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany Background: The aim of the ALPACA study was to investigate whether improved overall tolerability accompanied by prolonged treatment duration and increased efficacy can be achieved by alternating treatment cycles of Gem/nab-Pac and Gem monotherapy com-pared to standard continuous Gem/nab-Pac after a 3-month induction phase in patients with mPC. Methods: The randomized, multicenter phase 2 ALPACA trial of the German AIO study group enrolled patients with confirmed mPC in the first-line setting. After an in-duction phase with 3 cycles of standard dose Gem/nab-Pac (Gem 1000 mg/m 2 and nab-Pac 125 mg/m 2 on d1, 8, 15 of each 28-day cycle), patients were randomized (1:1) either to continue treatment with standard Gem/nab-Pac, or to receive alternating cycles of standard dose Gem/nab-Pac combination therapy and Gem monotherapy (Gem 1000 mg/ m 2 on d1, 8, 15 of each 28-day cycle). Primary study endpoint was overall survival (OS) after randomization. The trial was registered with ClinicalTrials.gov, NCT02564146. Results: Between May 2016 and May 2021, 325 patients were enrolled from 29 German centers. 6 of the enrolled patients did not start treatment within the study. Following 3 cycles of induction treatment, 174 patients (53.5%) could be randomized. Main reasons for premature dropout were death (24.8%), progression of disease (22.8%), and adverse events (15.9%). Median OS after randomization in the alternating treatment arm was comparable to the standard treatment arm (10.5 vs. 10.4 months; HR 0.903, 80% CI 0.723-1.128, p=0.5551). Likewise, median progression-free survival was comparable in both arms (5.5 vs. 5.3 months; HR 0.767, 95% CI 0.556-1.056, p=0.1017). Tolerability was improved for mPC patients treated with alternating cycles compared to standard therapy, especially regarding peripheral neuropathy (all grades, 44.7% vs. 52.5%), and occurrence of infections (all grades, 29.4% vs. 47.5%). 606 Second-line chemotherapy in elderly patients with advanced pancreatic Poster Session cancer: A mono-institutional retrospective experience. First Author: Giovanni Trovato, Oncologia Medica, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy Background: Results: 169 pts affected with APC received first-line chemotherapy and 61 of them (36%) received second-line therapy. The median age at diagnosis was 74 Years (70-83), 31 (50%) were female; ECOG PS was 0-1 in 44 pts (59%), 41% had at least 2 comorbidities. The regimens of chemotherapy used were: mFOLFOX (28; 46%), Gem-citabine (11; 18%), Capecitabine (15; 24.6%), FOLFIRI (6; 9.8%), mFOLFIRINOX (1; 1.6%). 4 pts (6.6%) had a partial response and 22 (36.1%) had a stable disease, with a disease control rate of 42.7%. The median follow-up was 22.8 months; median PFS2 was 4.5 months (IC 95%: 2.5-6.5) and median OS was 15.4 months (IC 95%: 7.2-23.6). At the univariable analysis, there was a statistically significant difference in mPFS2 according to ECOG PS (0-1 vs 2: 5.3 [IC 95%: 3.5-7.0] vs 2.2 [IC 95%: 1.2-5.4] months; p 0.02) and number of metastatic sites at the beginning of second line therapy (1 vs 2 or more: 5.8 [IC 95%: 4.8-6.7] vs 3.4 [IC 95%: 3.1-3.8] months; p 0.006). At the multivariable analysis, both number of metastatic sites and ECOG PS were confirmed associated with mPFS2.|

||||Model with education & income|| |---|---|---|---|---|

||||(Concordance= 0.65)||

|Demographics|||HR|p-value|

||n|%|||

|Sex|||||

|Male|35428|51.1|1.05|,0.01|

|Female|33934|48.9|Ref||

|Race/Ethnicity|||||

|White Non-Hispanic|53652|77.4|Ref||

|Black|6878|9.9|1.01|0.75|

|Hispanic/Latino|3814|5.5|0.88|,0.01|

|AAPI|2210|3.2|0.86|,0.01|

|Other|2808|4.1|0.98|0.27|

|Percent No High School Degree|||||

|Q1: < 84.7%|11904|17.2|0.99|0.58|

|Q2: 84.8 -90.9%|17065|24.6|1.04|0.01|

|Q3: 91.0 -95.0%|18042|26|1.04|,0.01|

|Q4: 95.0%+|14006|20.2|Ref||

|Unknown|8345|12|0.86|0.07|

|Median Income Quartiles|||||

|Q1: < $46277|9693|14|1.23|,0.01|

|Q2: $46277 -57856|13074|19|1.18|,0.01|

|Q3: $57857 -74062|14594|21|1.11|,0.01|

|Q4: $74063+|23468|33.8|Ref||

|Unknown|8533|12.3|1.25|0.01|

|*Concordance formodel without education & income = 0.648.|||||

|||||). Survival was| |---|---|---|---|---|

|evaluated using Kaplan-Meier curves and log-rank tests. Significance was set at|evaluated using Kaplan-Meier curves and log-rank tests. Significance was set at|evaluated using Kaplan-Meier curves and log-rank tests. Significance was set at|evaluated using Kaplan-Meier curves and log-rank tests. Significance was set at|evaluated using Kaplan-Meier curves and log-rank tests. Significance was set at|

|p,0.05. Results: When analyzing insurance status, patients with private insurance|p,0.05. Results: When analyzing insurance status, patients with private insurance|p,0.05. Results: When analyzing insurance status, patients with private insurance|p,0.05. Results: When analyzing insurance status, patients with private insurance|p,0.05. Results: When analyzing insurance status, patients with private insurance|

|had a statistically improved survival outcome (14.3 months) compared to those with|had a statistically improved survival outcome (14.3 months) compared to those with|had a statistically improved survival outcome (14.3 months) compared to those with|had a statistically improved survival outcome (14.3 months) compared to those with|had a statistically improved survival outcome (14.3 months) compared to those with|

|Medicare (11.3 months), Medicaid (9.2 months) and without insurance (11.8 months)|Medicare (11.3 months), Medicaid (9.2 months) and without insurance (11.8 months)|Medicare (11.3 months), Medicaid (9.2 months) and without insurance (11.8 months)|Medicare (11.3 months), Medicaid (9.2 months) and without insurance (11.8 months)|Medicare (11.3 months), Medicaid (9.2 months) and without insurance (11.8 months)|

|(p,0.05). Patients with private insurance had fewer positive regional lymph nodes (73),|(p,0.05). Patients with private insurance had fewer positive regional lymph nodes (73),|(p,0.05). Patients with private insurance had fewer positive regional lymph nodes (73),|(p,0.05). Patients with private insurance had fewer positive regional lymph nodes (73),|(p,0.05). Patients with private insurance had fewer positive regional lymph nodes (73),|

|lower grade/differentiation (5.80) and an average tumor size of 444.40 millimeters.|lower grade/differentiation (5.80) and an average tumor size of 444.40 millimeters.|lower grade/differentiation (5.80) and an average tumor size of 444.40 millimeters.|lower grade/differentiation (5.80) and an average tumor size of 444.40 millimeters.|lower grade/differentiation (5.80) and an average tumor size of 444.40 millimeters.|

|Patients treated at academic research programs had a statistically better survival|Patients treated at academic research programs had a statistically better survival|Patients treated at academic research programs had a statistically better survival|Patients treated at academic research programs had a statistically better survival|Patients treated at academic research programs had a statistically better survival|

|outcome (15.1 months) compared to patients treated at comprehensive community|outcome (15.1 months) compared to patients treated at comprehensive community|outcome (15.1 months) compared to patients treated at comprehensive community|outcome (15.1 months) compared to patients treated at comprehensive community|outcome (15.1 months) compared to patients treated at comprehensive community|

|(10.4 months) and integrated network (9.1 months) programs (p,0.001). Surgical|(10.4 months) and integrated network (9.1 months) programs (p,0.001). Surgical|(10.4 months) and integrated network (9.1 months) programs (p,0.001). Surgical|(10.4 months) and integrated network (9.1 months) programs (p,0.001). Surgical|(10.4 months) and integrated network (9.1 months) programs (p,0.001). Surgical|

|treatment had statistically improved survival outcomes compared to non-surgical|treatment had statistically improved survival outcomes compared to non-surgical|treatment had statistically improved survival outcomes compared to non-surgical|treatment had statistically improved survival outcomes compared to non-surgical|treatment had statistically improved survival outcomes compared to non-surgical|

|treatment (p,0.001) with the majority of these procedures being a partial pancrea-|treatment (p,0.001) with the majority of these procedures being a partial pancrea-|treatment (p,0.001) with the majority of these procedures being a partial pancrea-|treatment (p,0.001) with the majority of these procedures being a partial pancrea-|treatment (p,0.001) with the majority of these procedures being a partial pancrea-|

|tectomy and duodenectomy with a partial gastrectomy. More patients received surgical|tectomy and duodenectomy with a partial gastrectomy. More patients received surgical|tectomy and duodenectomy with a partial gastrectomy. More patients received surgical|tectomy and duodenectomy with a partial gastrectomy. More patients received surgical|tectomy and duodenectomy with a partial gastrectomy. More patients received surgical|

|intervention at academic research programs (p,0.001), and patients with private in-|intervention at academic research programs (p,0.001), and patients with private in-|intervention at academic research programs (p,0.001), and patients with private in-|intervention at academic research programs (p,0.001), and patients with private in-|intervention at academic research programs (p,0.001), and patients with private in-|

|surance predominately attended academic research programs (p,0.001).|surance predominately attended academic research programs (p,0.001).|surance predominately attended academic research programs (p,0.001).|surance predominately attended academic research programs (p,0.001).|surance predominately attended academic research programs (p,0.001).|

|Conclusions: 609 Poster Session Association of race and CA 19-9 nonproduction with limited pathologic response to neoadjuvant chemotherapy in patients with localized pancreatic cancer. First Author: Mary P. Martos, Department of Surgery, University of Miami Miller School of Medicine, Miami, FL Background: Black patients with pancreatic ductal adenocarcinoma (PDAC) are less likely to have major pathologic response (MPR) following induction chemotherapy compared to non-Black patients. Rare reports have suggested that Black patients are more likely to be CA 19-9 non-producers. We aimed to determine if disproportionate rates of CA 19-9 non-production underlie racial differences in neoadjuvant chemotherapy response in patients with localized PDAC. We also explored differences in somatic mutations between CA 19-9 producers (CAprod) and non-producers (CAnonprod). Methods: Black and White patients with localized PDAC receiving $ 2 cycles of neoadjuvant chemotherapy followed by pancreatectomy (2010-2019) at 7 high-volume centers were reviewed. Patients were categorized as CAprod (CA 19-9 . 5 U/mL) or CAnonprod (CA 19-9 # 5 U/mL). Uni-and multi-variable models evaluated differences in rates of CAnonprod by race, and the as-sociation of CAnonprod with MPR (CAP 0/1). The Pancreatic Cancer Action Network (PanCAN)'s SPARK health data platform which contains clinical and multi-omic data from the PanCAN Know Your Tumor program was queried to identify patients with CA 19-9 and genomic data. Fisher's exact test was used to compare differentially mutated genes be-tween CAprod and CAnonprod patients. Results: Our cohort included 385 (93.3%) CAprod and 30 (6.7%) CAnonprod. CAnonprod patients were more likely to be Black than CAprod (50.0% vs 12.5%, p,0.01). There were no other differences in demographic or clinical features between CAnonprod and CAprod. Most patients received FOLFIRINOX vs Gem-citabine based chemotherapy (60.3% CAprod vs. 56.7% CAnonprod, p=0.27) with a median number of 4.0 vs 5.0 cycles (p=0.83), respectively. Rate of MPR was significantly higher in patients with CAprod compared with CAnonprod patients (26.3% vs 7.7%, p=0.03). No CAnonprod patient had a complete pathologic response vs 28 (7.3%) of CAprod (p=0.12). CAnonprod was independently associated with decreased odds of MPR (OR 0.21, CI [0.04-0.99]). Black race was independently associated with increased odds of CAnonprod (OR Demographic and social vulnerability factors associated with late diagnosis Poster Session of gastrointestinal cancers. First Author: Muhammad Sohaib Khan, UT South-western Medical Center, Dallas, TX Factors associated with odds of metastatic cancer at diagnosis on multivariate logistic regression analysis performed for each cancer. Factors* (CI) Pancreatic Liver Colorectal Gastric Age in years Less than 35 35 -50 50 -65 More than 65 Ref 2.21 (1.90 -2.56) 2.52 (2.19 -2.91) 2.39 (2.07 -2.76) 0.64 (0.54 -0.74) 0.57 (0.49 -0.65) 0.67 (0.58 -0.77) 1.06 (1.007 -1.13) 0.90 (0.86 -0.96) 0.75 (0.71 -0.80) 0.71 (0.63 -0.79) 0.56 (0.50 -0.62) 0.44 (0.39 -0.49) Sex Male Female Ref 0.88 (0.86 -0.90) 0.84 (0.81 -0.88) 0.97 (0.95 -0.98) 0.87 (0.84 -0.90) 8.66, 610 Race Ref 1.15 (1.07 -1.23) 1.21 (1.18 -1.25) Not significant|||||

|White|1.06 (1.01 -1.11)|0.89 (0.83 -0.95)|0.89 (0.87 -0.92)|0.76 (0.72 -0.80)|

|Black|0.95 (0.90 -0.99)||||

|Asian|||||

|Insurance|Ref|1.76 (1.63 -1.91)|1.85 (1.78 -1.93)|1.76 (1.62 -1.91)|

|Private|1.34 (1.2''5 -1.45)|1.24 (1.19 -1.35)|1.76 (1.70 -1.81)|1.47 (1.39 -1.56)|

|Uninsured|1.30 (1.23 -1.38)||||

|Medicaid|||||

|Social factors|1.08 (1.003 -1.16)|1.41 (1.25 -1.58)|1.05 (1.0009 -1.10)|Not significant|

|Poverty below 150%|0.94 (0.90 -0.98)|Not significant|0.93 (0.90 -0.95)|0.88 (0.83 -0.94)|

|HH with aged > 65|||||

|The demographic charac-| |---|

|teristics (age, tobacco use, alcohol use, BMI); comorbidities (diabetes, acute/chronic|

|pancreatitis); pathology, treatment (chemotherapy regimen, radiation, surgery) and re-|

|currence free survival (RFS) and overall survival based on race were analyzed.|

|Results: The cohort (N=947) consisted of 147 (16%) African Americans (AA) and 775|

|(82%) Non-Hispanic Whites (NHW). The mean age at diagnosis was 68 years (610) among|

|AA and 70 years (611) in NHW. Thirty-seven (26%) of AA and 104 (14%) of NHW were|

|current smokers; 46 (33%) of AA and 323 (45%) of NHW consumed alcohol regularly.|

|Among AA, 32 (22%) were obese (BMI.30), compared to 194 (25%) in NHW. Other|

|comorbidities included diabetes (35% in AA vs. 32% in NHW) and acute/chronic pan-|

|creatitis (11% among AA vs. 9% among NHW). Eighteen percent (18%) of AA and 17% of|

|NHW had stage II disease, 16% and 12% had stage III and 48% in both had stage IV disease|

|respectively. The treatment modality consisted of chemotherapy (63% in AA vs. 66% in|

|NHW), surgery (25% in AA vs. 26% in NHW) and radiation (10% in AA vs. 12% in NHW). The|

|median time to treatment initiation was 30 (17, 41) months for AA and 26 (16, 40) months|

|for NHW. On univariate analysis, AA race was associated with younger age at diagnosis (p|

|0.043), higher current tobacco use (p 0.001), lower alcohol use (p 0.012), lower rates of|

|obesity (p 0|

|616|Poster Session| |---|---|

|Developing cell-free DNA (cfDNA) epigenetic signature (ep-Sig) for early|Developing cell-free DNA (cfDNA) epigenetic signature (ep-Sig) for early|

|detection of malignant transformation of intraductal papillary mucinous|detection of malignant transformation of intraductal papillary mucinous|

|neoplasms (IPMN).||

|The accuracy, specificity and sensitivity of the best-performing algorithm is reported. Results: This retrospective study included 50 healthy controls, 12 patients with chronic pancreatitis, and 42 patients with pancreatic cancer (12 stage I, 15 stage II, 9 stage III, 6 stage IV). Applying Wholomics´technology, an accuracy of 99.1% in differentiating the chronic pancreatitis and pancreatic cancer patients from the healthy controls was achieved. A specificity of 98.0% and a sensitivity of 100.0% were reached. Furthermore, pancreatic cancer patients and chronic pancreatitis patients were dif-ferentiated with 95.2% accuracy. 614 Liquid biopsies for faster diagnosis of suspected advanced pancreatic and Poster Session biliary tract cancers: ACCESS, a UK innovation programme. First Author: Lauren Jones, The Royal Marsden NHS Foundation Trust, London and Sutton, United Kingdom Background: Tissue diagnosis in biliary tract (BTC) and pancreatic (PC) cancer is challenging due to anatomical location and patient (pt) factors (frailty, sepsis); ap-proximately 25% of invasive biopsies are nondiagnostic, requiring repeat procedure. Most BTC and PC pts present with advanced disease. In stage III and IV solid tumours, Guardant 360 (G360) 74 gene panel liquid biopsy (LB) detects ctDNA in 80%/85% of BTC/ PC. ACCESS is a real-world innovation programme evaluating the impact of adding G360 to the current invasive diagnostic pathway for suspected BTC/PC in 6 hospitals in West London; (n=240). Methods: This is a pre-planned interim analysis of the first sequential 65 pts with G360 in ACCESS. Patients were age.18 years, ECOG # 2 with high ra-diographic suspicion of stage III/IV BTC or PC without histological diagnosis at reg-istration or other malignancies within 3 years. Positive LBs were reviewed at molecular tumour board with 4 pre-specified levels of diagnostic certainty: diagnostic/consistent/ possibly/not consistent. Tumour board review followed. Endpoints include repeat biopsy rate, change in time to diagnosis, quality of life, health economic assessment and patient satisfaction. Results: 64 patients were analysed (1 excluded). 50% female, median age 73 years (43-94), suspected cancer sites 14%/77%/9% BTC/PC/either BTC or PC. Suspected stage III/IV disease 38%/62%. ctDNA detection rate was 80%/100%/82% in overall cohort/BTC/PC. Most commonly detected LB alterations in suspected BTC/PC were TP53, APC, ATM, CDK/TP53, KRAS, CDKN2A, ARID1A. In BTC and PC, diagnostic method was liquid biopsy alone/liquid and tissue biopsy/tissue alone in 16%/49%/33%. 17% had repeat biopsy. Sensitivity/specificity of cancer diagnosis (all-comers) using liquid biopsy was 86% (95% CI 73.3-94.2)/38.5% (95% CI 13.9-68.4). Conclusions: There is a high ctDNA detection rate with high level diagnostic certainty, promising for future genomic transformation of BTC/PC diagnostic pathways, potentially reducing repeat invasive biopsies, speeding up diagnosis, facilitating precision therapy, with ACCESS||

|defining a blueprint for molecular integration of liquid biopsies. Full recruitment is|defining a blueprint for molecular integration of liquid biopsies. Full recruitment is|

|planned to complete in March 2024. Research Sponsor: NHS England.|planned to complete in March 2024. Research Sponsor: NHS England.|

|||||||||620||||Poster Session|| |---|---|---|---|---|---|---|---|---|---|---|---|---|---|

|||||||||Neoadjuvant chemotherapy vs upfront resection: A challenging choice in||||||

|||||||||resectable pancreatic ductal adenocarcinoma. First Author: Fatemeh Fekrmandi,||||||

|||||||||Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo,||||||

|||||||||NY||||||

|||||||||Results: Within 96 resectable patients, 45 (47%) underwent upfront surgery, 36 (37%) received||||||

|||||||||NACT followed by surgery and 15 (16%) only received chemotherapy. The majority were CA19-9||||||

|||||||||secretors (94%) with 54% lower values during chemotherapy. While 60% of patients experienced||||||

|||||||||up to 35% tumor size reductions on NACT, 20% had stable disease, and 20% showed progressive||||||

|||||||||disease. The patients who received NACT were significantly younger (p = 0.01), with higher||||||

|||||||||baseline CA19-9 (p , 0.01) and more frequently underwent stent placement (p = 0.01), table 1.||||||

|||||||||Median overall survival for the upfront surgery, NACT+surgery and chemotherapy groups were||||||

|||||||||32.8, 23.7 and 20.2 months (log-rank test p,0.01) subsequently. On univariate analysis initial||||||

|||||||||presentation with weight loss (p = 0.02, HR = 2.08) and high baseline CA19-9 (log2-scaled, p =||||||

|||||||||0.01, HR = 1.13) were predictive of worse overall survival. After adjusting for potential con-||||||

|||||||||founding variables, patients in chemotherapy group had significantly worse survival compared to||||||

|||||||||the upfront surgery group (P , 0.01, HR = 3.14). These 15 patients failed to undergo surgery due||||||

|||||||||to diverse reasons, including distant progression (7), local progression (3), performance status||||||

|||||||||decline or death during chemotherapy (2), refusal due to chemotherapy side effects (2), and||||||

|TTNT (mo) of first line treatments for each mutation group. G12C (n=33) G12V (n=629) G12D (n=904) G12R (n=324) Other G12/ 13 (n=36)|Other KRAS (n=130)|All KRAS (n=2056)|KRAS WT (n=416)|indecision and loss to follow-up (1). Conclusions: Characteristic Overall, N = 96 1 Upfront Surgery, N = 45 1 NACT+Surgery, N = 36 1 Chemotherapy, N = 15 1|p-value 2|||||||||

|Gemcitabine + nabPac (n=1248) FOLFIRINOX Gemcitabine (n=1104)|5.21 4.84 4.61 5.28 5.1|4.44 1.48 5.49|4.67 3.16 5.74|3.8 8.36 2.09|3.52 1.69 4.47|4.57 2.6 5.3|5.49 3.19 6.25|Age (yrs) Stent 9 placement Baseline CA19-|69 (63, 77) 13 (20%) 138 (17, 531)|73 (64, 79) 3 (8.1%) 52 (7, 179)|66 (61, 70) 10 (37%) 138 (22, 1,181)|70 (63, 75) 0 (NA%) 550 (338, 855)|0.013 0.010 , 0.001|

|(n=120)||||||||1 Median (IQR); n (%); 2 Kruskal-Wallis rank sum test; Fisher's exact test.||||||

|621|||||Poster Session|||||||||

|Relationship of tumor fraction in circulating tumor DNA (ctDNA) with prog-||||||||||||||

|nosis in patients with metastatic pancreatic cancer. First Author: Priyadarshini||||||||||||||

|Pathak, Massachusetts General Hospital, Boston, MA||||||||||||||

|Background: Real-world overall survival (rwOS) and time-to-next-treatment (rwTTNT) were evaluated||||||||||||||

|by ctDNA TF while controlling for relevant covariates. In parallel analyses, ctDNA TF||||||||||||||

|cutoffs of $1% and $10% were evaluated. Exploratory analysis of trichotomized ctDNA||||||||||||||

|TF at 1% and 10% was also performed. Results: 290 patients with mPDAC were included.||||||||||||||

|High ctDNA TF was associated with poor prognostic clinical features regardless of||||||||||||||

|cutpoint. High ctDNA TF also correlated with significantly reduced rwOS in univariable||||||||||||||

|analysis and after correction for covariates, regardless of cutpoint (1%: adj HR 1.33 [0.93-||||||||||||||

|1.90], adj P = 0.12; 10%: adj HR 1.91 [1.28-2.87] , adj P = 0.002). The same was observed||||||||||||||

|for rwTTNT (1%: adj HR 1.59 [1.14-2.22], adj P = 0.006; 10%: adj HR 2.18 [1.49-3.19] , adj||||||||||||||

|P , 0.001). When ctDNA TF was trichotomized, higher ctDNA TF groups had reduced||||||||||||||

|rwOS and rwTTNT in a stepwise manner in univariable analysis and after correction for||||||||||||||

|covariates (all vs ,1%; rwOS: adj HR for 1%-,10% 1.06 [0.71-1.59], adj P = 0.78; adj HR||||||||||||||

|for $10% 1.97 [1.26-3.09], adj P = 0.003; rwTTNT: adj HR for 1%-,10% 1.26 [0.87-1.84] ,||||||||||||||

|adj P = 0.22; adj HR for $10% 2.43 [1.60-3.70], adj P||||||||||||||

|154s|PANCREATIC CANCER|PANCREATIC CANCER| |---|---|---|

|Nutritional 624|Poster Session||

|||International Statistical Classification of Diseases (ICD-10) codes were employed to|

|||identify hospitalized patients admitted with primary diagnosis acute PE. Data regarding|

|||GI cancer diagnosis along with demographic information, baseline clinical character-|

|||istics, and outcome variables, including mortality, hospital length of stay, total hospital|

|||charges, complications and risk factors were collected and analyzed. Statistical analysis|

|||was performed using the survey procedures function in STATA v.17, with statistical|

|||significance defined by the t-test at a significance level of p , 0.05. Results: Among the|

|||181,060 patients admitted with primary diagnosis of acute pulmonary embolism, 550|

|||(0.3%) had underlying gastric cancer, 1,790 (0.98%) had pancreatic cancer, 875 (0.48%)|

|||had hepatobiliary cancer, and 2,600 (1.61%) had small intestine and colorectal cancer.|

|||Mortality was found to be significantly higher in all types of GI cancer, with gastric|

|||cancer demonstrating the highest mortality rate (10%). After adjusting for age, sex, race,|

|||payment category, comorbidities, and risk factors of PE, gastric cancer (OR 2.6; 95% CI:|

|||1.1-6.2) and pancreatic cancer (OR 2.2; 95% CI: 1.4-3.4) were found as independent risk|

|factors for mortality. 625 Poster Session 626|Poster Session||

|Predictive machine learning models for survival outcomes in patients with|Advanced pancreatic cancer outcomes and the impact of COVID-19 pan-||

|pancreatic cancer. First Author: Yang-Chen Shen, Institute of Behavioral Medicine,|demic: The experience of an academic cancer center. First Author: Christian||

|College of Medicine, National Cheng Kung University, Tainan, Taiwan||Adams-Carey, University of Cincinnati College of Medicine, Cincinnati, OH|

|Background: Identifying prognostic markers is essential for accurately assessing risk|Background:||

|levels in pancreatic cancer patients, leading to more personalized treatment ap-|||

|proaches. In light of this, our study endeavors to build a survival prediction model for|||

|pancreatic cancer patients using various machine learning (ML) techniques, taking into|||

|account both clinical and inflammatory factors. Methods: The research included 311|||

|pancreatic cancer patients on a prospective basis. Their data was sourced from the|||

|Clinical Data Warehouse of National Cheng Kung University Hospital. For the purpose of|||

|predicting 6 and 12-month survival, patients were randomly allocated into training,|||

|validation, and test groups in an 8:1:1 ratio. We utilized machine learning techniques and|||

|assessed them on the QOCA Aim (Quanta Omni Cloud Care for AI Medical Platform,|||

|version 2.0) platform. The model's effectiveness was gauged using the area under the|||

|receiver operating characteristic curve (AUC). Results: The cohort exhibited a mean age|||

|of 63.5 years with a standard deviation of 11. The median overall survival was|||

|documented at 16.8 months (95% confidence interval [CI] = 15.6-18). Analytical|||

|evaluation indicated that the optimal model for prognostication of 6-month survival was|||

|the balanced bagging classifier, yielding an AUC of 93.7%. Conversely, for the 12-month|||

|survival prediction, the k-nearest neighbors (kNN) classifier was superior, demonstrating|||

|an AUC of 86.1%. Subsequent variable importance analysis elucidated that salient|||

|predictors encompassed C-Reactive protein (CRP), surgical intervention, carbohydrate|||

|antigen (CA)19-9, age at diagnosis, and the neutrophil-lymphocyte ratio (NLR).|||

|Conclusions: The findings indicated that machine learning can be employed to develop|||

|high-efficacy predictive models for survival in pancreatic cancer patients. Such models|Conclusions: This is the first report to analyse optimum utility of SIRT with chemo-||

|offer promise for enhanced risk categorization and personalized prognostic assessment|therapy in metastatic PDAC. Our data suggest SIRT in combination with 1st-line||

|in this patient cohort. Research Sponsor: National Science and Technology Council,|platinum agents contribute to the best outcomes in the setting and warrants further||

|Taiwan.||study. Research Sponsor: None.|

|of pts| |---|

|received FFX/mFFX, 2% received FOLFIRI (omitting oxaliplatin), and 1% received other|

|combinations. The number of pts in treatment declined over subsequent administrations,|

|as did the number receiving FFX: by the 10 th administration, 390 pts were treated, with|

|74% receiving mFFX, 13% FOLFIRI, 5% FOLFOX (omitting irinotecan), and 7% other combinations. At the 15 th administration, 149 pts continued treatment, with 36% receiving|

|mFFX, 44% FOLFIRI, 5% FOLFOX, 8% 5FU + leucovorin, and 7% other (either 5FU alone or|

|with oxaliplatin and/or irinotecan). Median 6-week dose density was 69% for 5FU (IQR:|

|40-93%), 100% for leucovorin (IQR: 66-133%), 83% for irinotecan (IQR: 56-130%), and|

|99% for oxaliplatin (IQR: 68-127%).|

|therapy for FFX-only vs. FFX + GnP pts (IR=0.037 vs. 0.027; p=.041). AEs based on lab values were higher per pt-month of 1L therapy for FFX-only vs. FFX + GnP pts for grade 3/4 thrombocytopenia (IR=0.012 vs. 0.006, p=.013), grade 1/2 anemia (IR=0.203 vs. 0.142, p,.001), grade 1/2 and 3/4 hypokalemia (IR=0.099 vs. 0.074, p,.001; IR=0.040 vs. 0.028, p=.010), grade 1/2 elevated ALT (IR=0.138 vs. 0.098, p,.001), grade 1/2 and 3/4 elevated AST (IR=0.150 vs. 0.109, p,.001; IR=0.018 vs. 0.011, p=.021), and grade 1/2 and 3/4 elevated ALP (IR=0.172 vs. 0.123, p,.001; IR=0.034 vs. 0.025, p=.035). 3%) underwent surgery of the primary site, 72 (3.2%) received adjuvant chemotherapy, and 9 (0.4%) received adjuvant radiation. Surgery alone was associated with the longest median survival (198.5 months) compared to the other treatments (Adjuvant chemotherapy=155.3 months, Adjuvant radiation=122.7 months, No surgery=73.95 months; p,0.05).| |---|

|633|Poster Session| |---|---|

|Trends in incidence and survival of early-stage pancreatic ductal adeno-|Trends in incidence and survival of early-stage pancreatic ductal adeno-|

|carcinoma in the United States. First Author: Gerardo Perrotta, Cedars-Sinai|carcinoma in the United States. First Author: Gerardo Perrotta, Cedars-Sinai|

|Medical Center, Los Angeles, CA||

|Background: Results: From 2001 to 2020,||

|the age-adjusted incidence rate of early-stage PDAC increased from 1.1 to 2.8 (per|the age-adjusted incidence rate of early-stage PDAC increased from 1.1 to 2.8 (per|

|100,000 person-years), while locally advanced PDAC increased from 3.6 to 4.3, and from|100,000 person-years), while locally advanced PDAC increased from 3.6 to 4.3, and from|

|6.4 to 7.7 for metastatic PDAC (all p,0.01). The Annual Percent Change (APC) was 5.7|6.4 to 7.7 for metastatic PDAC (all p,0.01). The Annual Percent Change (APC) was 5.7|

|for Early-Stage PDAC (95% CI 5.1-6.4), 1.4 for locally advanced (95% CI 0.8-1.9), and 0.8|for Early-Stage PDAC (95% CI 5.1-6.4), 1.4 for locally advanced (95% CI 0.8-1.9), and 0.8|

|for Metastatic PDAC (95% CI 0.6-1.1). The incidence rate ratio (IRR) almost doubled for|for Metastatic PDAC (95% CI 0.6-1.1). The incidence rate ratio (IRR) almost doubled for|

|early-stage PDAC, increasing from 0.10 to 0.19. Conversely, for metastatic and locally|early-stage PDAC, increasing from 0.10 to 0.19. Conversely, for metastatic and locally|

|advanced stages, the IRR decreased from 0.58 to 0.52 and 0.32 to 0.29, respectively.|advanced stages, the IRR decreased from 0.58 to 0.52 and 0.32 to 0.29, respectively.|

|Survival analysis revealed 5-year overall survival rates of 74%, 69%, 57%, and 33% for|Survival analysis revealed 5-year overall survival rates of 74%, 69%, 57%, and 33% for|

|stages 0, IA, IB, and IIA, respectively, with an overall improvement from 2004 to 2015.|stages 0, IA, IB, and IIA, respectively, with an overall improvement from 2004 to 2015.|

|This increase was consistent among all age groups, genders, and races. Stages IA and IB|This increase was consistent among all age groups, genders, and races. Stages IA and IB|

|demonstrated larger increases 45.9% and 56.6%, respectively (IA: 47% in 2004 to 75% in|demonstrated larger increases 45.9% and 56.6%, respectively (IA: 47% in 2004 to 75% in|

|2015; IB: 38% in 2004 to 68% in 2015)||

|The median follow-up was 78 months for our cohort while median overall survival (OS) from diagnosis was 47 months (95%CI=34-79 months). The median duration for Br-M detection from PDAC diagnosis was 24 months, while median OS from Br-M diagnosis was only 3 months (95% CI=2-6 months). 48% (n=21) had metastatic disease at diagnosis. Histological grade was assessed for 37 patients of which 51% (n=19) patients had poor differentiation, while 46% had moderate differentiation, and only 1 patient had a well differentiated tumor. Most of our patients received multiple lines of chemotherapy prior to Br-M development, with a median of 4 chemotherapy regimens received. The majority (73%, n=32) had ECOG performance score of 0 or 1 at Br-M diagnosis, also 82% (n=36) patients had elevated CA19-9 prior to Br-M. Metastases to more than one site other than the brain were detected in 73% (n=32), lung metastasis was the most frequently detected, followed by liver then bone (71% n=31, 66% n=29, 39% n=17, respectively). The frontal lobe was the most frequently affected (34%, n=15) followed by cerebellar affection (23%, n=10). Leptomeningeal affection was observed in (18%, n=8) patients. Targeted clinical mutation testing was done for 17 patients, KRAS was mutated in 95% (n=16) of patients, with G12V in 47% (n=8) of patients, G12D in 29% (n=5), and G12R in 18% (n=3), the second most prevalent mutation was TP53, 70% (n=12) then CDKN2A in 18% (n=3) of the patients. Surgical resection for Br-M was performed for 5 patients who had better median OS of 8.6 months followed by patients who underwent stereotactic radiosurgery (n=11) with median OS of 3.3 months, and patients who received Poster Session Associations between BMI, morphomics and survival in 528 patients with metastatic pancreatic cancer. First Author: Valerie Gunchick, Vanderbilt University, Nashville, TN Background: Kaplan-Meier plots were created to evaluate median survival times between those in the highest and lowest tertiles (R v4.3.1). Results: We did not observe an association between BMI and PDA patient survival: HR (95% CI) comparing BMI $30 (obese) to 18.5-24.9 (healthy weight), PFS 0.96 (0.66, 1.39), p-trend=0.80; OS 0.87 (0.64, 1.18), p-trend=0.30. However, multiple mor-phomic variables were significantly associated with PFS and/or OS in univariate and multivariate models when comparing the highest to lowest tertile. More subcutaneous fat was associated with longer median OS (12.4 vs 10.5 mos, p=0.006; HR (95% CI) 0.41 (0.25-0.638 G12D (n=66, 40.7% of KRAS mutations) followed by G12V (n=58, 35.8%), G12R (n=15, 9.3%), and Q61H (n=10, 6.2%). Among KRAS mutations allelic subtypes, KRAS G12D and Q61 mutations had significantly worse OS with median OS 13 and 10 months re-spectively (P ,0.001). The most frequently co-occurring mutations detected in KRAS positive patients were TP53 (n=126, 77.8%), CDKN2A (n=34, 21%), SMAD4 (n=33, 20.4%), and ARID1A (n=12, 7.4%). Examining the prognostic significance of co-occurring mutations among patients with metastatic disease, only detection of co-occurring CDKN2A mutation was associated with worse OS as compared to patients with KRAS mutations without co-occurring CDKN2A mutations (median OS 8 vs 14 months, HR=2, Vascular resection for pancreas cancer: Ten-year real-world experience from a single high-volume center. First Author: David Henault, University Health Network, Toronto, ON, Canada Background: In pancreatic ductal adenocarcinoma (PDAC), to identify prognostic factors for surgically treated patients, including vascular resections. Methods: Retrospective review (2011 -2023) of pathologically proven PDAC treated with curative-intent surgery (n = 715) at a high-volume cancer center. We tested associations between clinico-pathological and radiological data, perioperative therapy, time to recurrence (TTR) and overall survival (OS). Results: Demographic and clinicopathological variables were comparable to published surgical cohorts. Initial NCCN radiological staging was 533 (74.5%) resectable, 98 (13.7%) borderline, and 84 (11.7%) locally advanced PDAC. There were 467(65.3%) pancreaticoduodenectomies, 104 (14.5%) distal pancreatectomies, 31 (4.3%) total pancreatectomies and 112 (15.7%) aborted procedures, mostly due to metastatic disease (82.1%). Of the 603 resected cases, 351 (58.2%) were non-vascular resections (NVR), 181 (30.0%) venous-only resections (VR), and 70 (11.8%) were arterial 6 venous resections (AR). Median length of stay was 8 days, ICU admission rate was 6.1% (n = 37), readmissions occurred in 114 (18.9%) cases and reoperations in 47 (7.8%) cases. The 90-day mortality rate was 3.2% (n = 19) and the 5-year OS was 20.7%. Perioperative chemotherapy was given to 258 (78.4%) NVR, 129 (75.9%) VR and 60 (93.8%) AR. Perioperative chemoradiation was given to 20 (6.8%) NVR, 34 (21.0%) VR and 43 (66.1%) AR. Median TTR and OS did not significantly differ by initial NCCN staging or type of pancreas resection. Median TTR and OS were significantly shorter for VR (14.5 and 22.7 months) compared to NVR (18.6 and 30.5 months, p,0.001) and AR (20.6 months, p = 0.004 and 30.9 months, p = 0.017). Patients who received chemotherapy or chemo-radiation had significantly longer TTR (20.1 vs. 10.2 months, p,0.001 and 25.3 vs. 16.4 months, p,0.001) and OS (31.5 vs. 17.2 months, p,0.001 and 35.5 vs. 27.5 months, p=0.030) compared to patients not receiving any therapy. In multivariate analysis, when controlling for perioperative therapy and usual clinicopathological factors, vascular re-Poster Session 95%CI=1.1-3.5, P value=0.015). Conclusions: 637 whole brain radiation (n=20) with median OS of 2.8 months. Conclusions: 636 Poster Session Results: Liquid biopsies were performed for 313 patients with PDAC; 58% (n=181) were diagnosed with stage IV disease. The median follow-up was 25 months, with median OS 24 months (95%CI=21-29). Overall, 52% (n=162) tested positive for KRAS mutations. Among patients with metastatic disease at diagnosis (n=181), 66.7% (n= 120) tested positive for KRAS mutations. In contrast, only 31.8% (n= 42) of patients with stage I to III disease at diagnosis (n=132) tested positive. Among patients with metastatic disease, those with KRAS positive disease had sig-nificantly shorter OS (median OS 13 vs 27 months, HR=2.7, 95%CI=1.7-4.3, P,0.0001). In patients with non-metastatic disease, the median OS was 28 vs 43 months, re-spectively (HR=1.7, 95%CI=0.97-2.8, P=0.064). The most frequent KRAS mutation was Results: We identified 69 EOPC pts who were evaluated by genetics. Baseline char-acteristics include median age of 55 years (range 25-60) with 52% male, 48% white, 23% black, and 52% with current or prior tobacco use. At presentation, 41% and 59% had metastatic and non-metastatic disease, respectively. Eight (12%) pts declined germline testing. Among the 61 who underwent germline testing, 30 (49%) pts had negative testing, 21 (34%) had only variants of uncertain significance, and 10 (16%) had pathogenic/likely pathogenic germline variants (PVs). The most frequently seen PVs were ATM (20%), BRCA1 (20%), BRCA2 (10%), MLH1 (10%), NTHL1 (10%), PTCH1 (10%), CFTR (10%) and one (10%) with multiple pathogenic germline findings including RAD51 and BRCA1. 640 Poster Session| |---|

|642|Poster Session| |---|---|

|Results: Among the 139 PMDC and 141 non-PMDC patients, the median number of days between referral and treatment initiation was similar (PMDC: 33 days (IQR: 22, 44) vs. non-PMDC: 32 days (IQR: 23, 42); p .0.9). The median time between diagnosis and treatment initiation was also similar (PMDC: 28 days (IQR: 19, 37) vs. non-PMDC: 30 days (IQR: 21, 37); p=0.4). Of note, PMDC patients received more supportive care visits within 30 days of diagnosis (PMDC: 2 (IQR: 1, 2) vs. non-PMDC: 0 (IQR: 0, 1) ; p ,0.001) and completed more visits with cancer providers (PMDC: 7 (IQR: 6, 8) vs. non-PMDC: 5 (IQR: 4, 7); p ,0.001) compared with non-PMDC patients. In addition, PMDC patients also required fewer physical trips to the medical center (PMDC: 4 (IQR: 3, 5) vs. non-PMDC: 4 (IQR: 3, 6); p ,0.001). Conclusions: Pancreatic cancer patients seen in a one-day multi-disciplinary clinic attend a greater number of coordinated appointments and receive more supportive care services with fewer physical trips to the medical center compared with patients not seen in a PMDC clinic. Future studies should focus on the long-term patient-centric benefits of a multi-disciplinary approach for cancer patients. Research Sponsor: None. Collective. First Author: Joseph M. Herman, Northwell Health Cancer Institute, Lake Success, NY cohort. Early results of a pancreas cancer learning health network: Canopy Cancer Cardiometabolic risk comorbidities in exocrine pancreatic insufficiency compared to patients with cancer: A single centered observational retro-spective cohort study. First Author: James Peeples, Department of Internal Medicine, Ochsner Health, New Orleans, LA Background: Exocrine pancreatic insufficiency (EPI) is characterized by inadequate secretion of digestive enzymes. EPI is associated with increased risk for pancreatic cancer as well as increased risk for diabetes and consequently cardiometabolic (CM) risk equivalents. Emerging data suggest patients with cancer also have increased CM risk equivalents. To explore the cardiovascular risk associated with both EPI and cancer, we sought to describe and compare CM comorbidities and surrogates in patients with EPI vs cancer. Methods: A retrospective observational electronic chart analysis was done at Ochsner Health, Louisiana, spanning records from January 2017-2020 comparing two cohorts: patients with EPI (n=677) and patients with Cancer (n=1432). Results: The Cancer cohort was older (65.1 6 11.9 yrs) than the EPI cohort (54.2 6 17.6 yrs) (p , 0.05). The Cancer cohort had higher AST levels (63.2 6 106.2 U/L [nl 8-33 U/L] at start, 84.9 6 447.3 U/L at end) vs the EPI cohort (50.2 6 86.9 U/L at start, 65.4 6 368.9 U/L at end) (p , 0.05). The Cancer cohort also had higher ALT levels (69 6 111.4 U/L (nl 7-55 U/L) at start, 58.5 6 141.2 U/L at end) vs the EPI cohort (48.7 6 79.5 U/L at start, 41.4 6 100.3 U/L at end) (p , 0.05). No significant differences were seen in Cancer cohort vs EPI cohort for A1c, TG, amylase, lipase, cholesterol, uric acid, tobacco/alcohol use, or blood pressure levels. Within the Cancer cohort, there was an increase in neuropathy (11% at the start vs 26.9% at end [p , 0.05] ), CHF (3.63% at the start vs 11.5% at end [p , 0.05]), and HTN prevalence (29.9% at the start vs 66.1% at end [p , 0.05] ). Cancer patients also had decreased weight (175.2 6 46.5 lbs at start, 163.8 6 43.4 lbs at end [p , 0.05]) and BMI (27.3 6 6.5 at start, 25.7 6 6.4 at end [p , 0.05] ). Among the general cancer cohort, no statistically different changes were seen in hypoglycemia, DKA, retinopathy, nephropathy, ESRD, dialysis, HLD, NAFLD, OSA, CAD, CVD, PAD, hyperuricemia, or gout prevalence over the period of observation or in comparison to EPI Background:||

|This current study substitutes Nal-IRI for traditional irinotecan in the mFOLFIRINOX regimen (NALIRIFOX) and aims to demonstrate safe neoadjuvant delivery. NALIRIFOX is currently under review by the FDA for frontline mPDAC. Methods: This phase 2, open-label, mul-ticenter single-arm study enrolled adult patients (pts) with operable PDAC, resectability (borderline vs. resectable) confirmed by multiD conference, adequate organ function, and ECOG performance status (0-1). Pts received NALIRIFOX (per NAPOLI-3) every 2 wks x 4 mo followed by repeat imaging and surgical resection 4-8 wks later. Primary endpoint is the composite 30 day post-op major complication rate (hospital re-admission, death, second surgery, procedure or major complication extending hospital stay). A sample size of 25 pts will detect a 20% reduction in 1°endpoint (from 30% to 10%; 1-sided exact test; a=0.05; b=.8). Toxicity, treatment completion, R0 resection, clinical, biochemical and radiographic response rates and QOL during treatment (FACT-G) are 2°endpoints. Serial microbiota specimens have been collected for exploratory analysis. Results: From May 2019 to Feb 2023, 45 pts were enrolled from 4 centers. Median age was 63 (41-76), majority women (53%), white (89%) with borderline (n=30) or resectable (n=15) disease. All 45 pts initiated treatment with 34 proceeding to surgery and 29 completing definitive resection. Most common grade .3 AEs included non-febrile neutropenia (41%), diarrhea (30%), and anorexia (22%). Those not obtaining definitive resection had progressive disease (radiographic n=6; intra-op n=5), physician change of tx (n=2), toxicity (n=2; CMV colitis and TPN requirement/ sepsis) or consent withdraw (n=1). Three (10%) pts had a post-op major complication (p=0.012). One pt died from post-op bleeding complications. Resections included both borderline (n=15) and resectable (n=14) initial disease with overall R0 resection rate of 89%. Conclusions: 656 Incorporating stereotactic body radiation therapy for inoperable pancreatic Poster Session cancer. First Author: Alexander Lukez, Fox Chase Cancer Center, Philadelphia, PA Results. Unadjusted Adjusted There was no significant difference found in overall survival of patients on metformin (n=132, mean overall survival (mOS) 6.68 months), compared to those not on metformin (n=498, average survival 7.44 months), p=0.989. Further subgroup analysis based on cancer staging showed that patients with resectable pancreatic cancer (AJCC stage I-IIA, n=140), who did not use metformin (n=106) had a mOS of 12.98 months compared to 9.71 months for metformin users (n=34), p=0.438. For patients with locally advanced disease (AJCC stage IIB-III, n=125), the average mOS of non-metformin users (n=103) was 11.10 months compared to 10.73 months for metformin users (n=22), p=0.803. For patients with metastatic disease (AJCC stage IV, n=365), the average survival of non-metformin users (n=289) was 3.48 months compared to 4.26 months for metformin users (n=76), p=0.803. Diabetic patients (n=195) on metformin (n=132) compared to those not on metformin (n=63), did not show significant survival difference (mOS 6.68 months vs 6.61 months respectively, p =0.602). Conclusions: 661 Poster Session||||||| |---|---|---|---|---|---|---|

||||HR (95% CI)|p-value|HR (95% CI)|p-value|

|||Intervention for local progression (CHT alone reference group)|||||

|||CHT + SBRT|1.24 (0.48 -3.18)|0.66|0.28 (0.06 -1.32)|0.11|

|||SBRT|0.12 (0.02 -0.85)|0.03|0.27 (0.004 -2.03)|0.20|

|||Local progression (CHT alone reference group)|Local progression (CHT alone reference group)|Local progression (CHT alone reference group)|Local progression (CHT alone reference group)||

|||CHT + SBRT|0.82 (0.34 -1.94)|0.65|0.73 (0.22 -2.49)|0.62|

|||SBRT|0.24 (0.09 -0.66)|0.006|0.41 (0.11 -1.49)|0.17|

|653 658|Poster Session Poster Session|654 659|||Poster Session Poster Session|Poster Session Poster Session|

|Anlotinib plus chemotherapy as first-line therapy for patients with gastro-The interim analysis of a single-arm, open-label, phase II study investigating|BNT321, a novel monoclonal antibody targeting sialyl Lewis A: Phase 1 Preliminary results of a phase II study of surufatinib plus sintilimab, nab-|BNT321, a novel monoclonal antibody targeting sialyl Lewis A: Phase 1 Preliminary results of a phase II study of surufatinib plus sintilimab, nab-|BNT321, a novel monoclonal antibody targeting sialyl Lewis A: Phase 1 Preliminary results of a phase II study of surufatinib plus sintilimab, nab-|BNT321, a novel monoclonal antibody targeting sialyl Lewis A: Phase 1 Preliminary results of a phase II study of surufatinib plus sintilimab, nab-|BNT321, a novel monoclonal antibody targeting sialyl Lewis A: Phase 1 Preliminary results of a phase II study of surufatinib plus sintilimab, nab-|BNT321, a novel monoclonal antibody targeting sialyl Lewis A: Phase 1 Preliminary results of a phase II study of surufatinib plus sintilimab, nab-|

|intestinal tumor with unresectable liver metastasis: Updated results from a ALLEN regimen (durvalumab plus albumin paclitaxel and lenvatinib) in|monotherapy and combination with mFOLFIRINOX in patients with ad-paclitaxel and gemcitabine (AG) as first-line therapy in patients (pts) with|monotherapy and combination with mFOLFIRINOX in patients with ad-paclitaxel and gemcitabine (AG) as first-line therapy in patients (pts) with|monotherapy and combination with mFOLFIRINOX in patients with ad-paclitaxel and gemcitabine (AG) as first-line therapy in patients (pts) with|monotherapy and combination with mFOLFIRINOX in patients with ad-paclitaxel and gemcitabine (AG) as first-line therapy in patients (pts) with|monotherapy and combination with mFOLFIRINOX in patients with ad-paclitaxel and gemcitabine (AG) as first-line therapy in patients (pts) with|monotherapy and combination with mFOLFIRINOX in patients with ad-paclitaxel and gemcitabine (AG) as first-line therapy in patients (pts) with|

|multi-cohort, multi-center phase II trial ALTER-G-001-cohort C. First Author: patients with metastatic pancreatic cancer (mPC). First Author: Meixia Chen,|vanced CA19-9 expressing cancers. First Author: Eileen Mary O'Reilly, locally advanced or metastatic pancreatic adenocarcinoma (mPDAC). First|vanced CA19-9 expressing cancers. First Author: Eileen Mary O'Reilly, locally advanced or metastatic pancreatic adenocarcinoma (mPDAC). First|vanced CA19-9 expressing cancers. First Author: Eileen Mary O'Reilly, locally advanced or metastatic pancreatic adenocarcinoma (mPDAC). First|vanced CA19-9 expressing cancers. First Author: Eileen Mary O'Reilly, locally advanced or metastatic pancreatic adenocarcinoma (mPDAC). First|vanced CA19-9 expressing cancers. First Author: Eileen Mary O'Reilly, locally advanced or metastatic pancreatic adenocarcinoma (mPDAC). First|vanced CA19-9 expressing cancers. First Author: Eileen Mary O'Reilly, locally advanced or metastatic pancreatic adenocarcinoma (mPDAC). First|

|Junwei Wu, Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University Department of Bio-therapeutic, The First Medical Center, Chinese PLA General Hospital,|Memorial Sloan Kettering Cancer Center, New York, NY Author: Dong-Sheng Zhang, Department of Medical Oncology, Sun Yat-sen University||||||

|School of Medicine, Shanghai, China Background: Advanced gastrointestinal (GI) tumors, such as colorectal, gastric and Beijing, China Background: Metastatic pancreatic cancer is a leading cause of cancer death worldwide|Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Inno-Background: BNT321 is a high affinity human monoclonal antibody targeting the sialyl Lewis A epitope of CA19-9. This Phase 1/1b dose escalation/expansion study investigated vation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China|Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Inno-Background: BNT321 is a high affinity human monoclonal antibody targeting the sialyl Lewis A epitope of CA19-9. This Phase 1/1b dose escalation/expansion study investigated vation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China|Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Inno-Background: BNT321 is a high affinity human monoclonal antibody targeting the sialyl Lewis A epitope of CA19-9. This Phase 1/1b dose escalation/expansion study investigated vation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China|Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Inno-Background: BNT321 is a high affinity human monoclonal antibody targeting the sialyl Lewis A epitope of CA19-9. This Phase 1/1b dose escalation/expansion study investigated vation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China|Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Inno-Background: BNT321 is a high affinity human monoclonal antibody targeting the sialyl Lewis A epitope of CA19-9. This Phase 1/1b dose escalation/expansion study investigated vation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China|Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Inno-Background: BNT321 is a high affinity human monoclonal antibody targeting the sialyl Lewis A epitope of CA19-9. This Phase 1/1b dose escalation/expansion study investigated vation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China|

|pancreatic cancers (CRC, GC, and PC), and esophageal squamous cell carcinoma (ESCC), with limited treatment options. Durvalumab, the anti-PD-L1 inhibitor has revealed|BNT321 as monotherapy and in combination with mFOLFIRINOX (mFFX) in patients (pts) Background: Advanced pancreatic adenocarcinoma (PDAC) had poor survival and limited|BNT321 as monotherapy and in combination with mFOLFIRINOX (mFFX) in patients (pts) Background: Advanced pancreatic adenocarcinoma (PDAC) had poor survival and limited|BNT321 as monotherapy and in combination with mFOLFIRINOX (mFFX) in patients (pts) Background: Advanced pancreatic adenocarcinoma (PDAC) had poor survival and limited|BNT321 as monotherapy and in combination with mFOLFIRINOX (mFFX) in patients (pts) Background: Advanced pancreatic adenocarcinoma (PDAC) had poor survival and limited|BNT321 as monotherapy and in combination with mFOLFIRINOX (mFFX) in patients (pts) Background: Advanced pancreatic adenocarcinoma (PDAC) had poor survival and limited|BNT321 as monotherapy and in combination with mFOLFIRINOX (mFFX) in patients (pts) Background: Advanced pancreatic adenocarcinoma (PDAC) had poor survival and limited|

|20%-50% with liver metastases (LMs) have a poor prognosis. Previous trials showed that remarkable efficacy in solid malignancies including hepatobiliary cancers. We|with advanced CA19-9 expressing cancers. Methods: Eligible pts: progressive CA19-9 therapeutic options. Surufatinib is a potent, small-molecule tyrosine kinase inhibitor (TKI),|with advanced CA19-9 expressing cancers. Methods: Eligible pts: progressive CA19-9 therapeutic options. Surufatinib is a potent, small-molecule tyrosine kinase inhibitor (TKI),|with advanced CA19-9 expressing cancers. Methods: Eligible pts: progressive CA19-9 therapeutic options. Surufatinib is a potent, small-molecule tyrosine kinase inhibitor (TKI),|with advanced CA19-9 expressing cancers. Methods: Eligible pts: progressive CA19-9 therapeutic options. Surufatinib is a potent, small-molecule tyrosine kinase inhibitor (TKI),|with advanced CA19-9 expressing cancers. Methods: Eligible pts: progressive CA19-9 therapeutic options. Surufatinib is a potent, small-molecule tyrosine kinase inhibitor (TKI),|with advanced CA19-9 expressing cancers. Methods: Eligible pts: progressive CA19-9 therapeutic options. Surufatinib is a potent, small-molecule tyrosine kinase inhibitor (TKI),|

|anlotinib plus chemotherapy has promising clinical activity and a tolerable safety profile for advanced CRC and ESCC, especially with LMs. In this phase II trial, we assessed the efficacy and safety of anlotinib plus chemotherapy as first-line treatment for LMs GI tumors. Methods: Patients with unresectable LMs GI tumors and without previous systemic treatment would be divided into cohort A (CRC), cohort B (ESCC), and cohort C (other GI tumors, such as PC, GC, biliary tract cancer (BTC), etc.). In cohort C, patients received induction therapy: anlotinib plus standard chemotherapy. Patients without PD and radical resection received anlotinib and metronomic capecitabine (500 mg, PO, BID, days 1-21, q3w) maintenance until PD or unacceptable toxicity. The primary endpoint was ORR (RECIST 1.1). Secondary endpoints were DoR, PFS, OS, DCR, radical resection rate for LMs, and safety. Results: As of September 14, 2023, 41 patients were enrolled in cohort C (29 PC, 6 GC, 5 BTC, and others), the median age was 64 years (34-74), 63.4% male, 92.7% ECOG-PS 1 and 56.1% had LMs only. The majority of the pancreatic cancer patients (26/29) received gemcitabine plus nab-paclitaxel chemotherapy combination with anlotinib as induction therapy. After induction therapy, 4 patients (1 PC, 2 GC, 1 BTC) received surgical resection. Of 37 evaluable patients in cohort C, ORR and DCR were 45.9% and 86.5% (PR, n=17; SD, n=15, 12 SD had reduced tumor size). Of 25 evaluable pancreatic cancer patients, 12 had PR, 10 had SD, ORR and DCR were 48% and 88%. According to the Kaplan-Meier method, the median DoR was 4.2 months (95%CI, 1.7-6.6) and the median PFS was 5.5 months (95%CI, 4.7-6.3). 37 patients in cohort C had TEAEs conducted a study to evaluate the efficacy and safety of a combination therapy of Durvalumab, Albumin paclitaxel and Lenvatinib (ALLEN Regimen) in patients with mPC. Methods: This open-label, single-center, single-arm, phase Ⅱ clinical trial investigated patients with metastatic pancreatic cancer. Durvalumab (1000mg IV, q3w), albumin paclitaxel(180-220 mg/m 2 IV q3w) and lenvatinib (8mg PO QD) were given regularly until disease progression. The primary endpoint was objective response rate (ORR) evaluated by investigators according to RECIST 1.1. The secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and treatment-related adverse events (TRAEs). Results: Between September 2021 and September 2023, seventeen patients with ECOG score 0-2 were enrolled, including 8 patients (47%) who were refractory to at least one systemic chemotherapy.The median follow-up was 6.0 months (95% CI 4.0, 8.4). 17 patients were evaluable, with a median age of 58 years. 9 patients (52.9%) were male. The ORR and DCR were 64.7% and 94.1%, respectively. The median PFS was 7.8 months (95% CI 3.1, 11.4), and the median OS was 8.1 months (95% CI 4.7, 13.5). TRAEs (all grades) occurred in 16 (94.1%) patients. The most common grade 1-2 TRAEs were nausea 8 (47.1%), diarrhoea 5(29.4%), peripheral sensory neu-ropathy 3 (17. 6% ) and hypertension 3(17.6% ). No grade 3 or higher TRAEs occurred. Conclusions: The ALLEN regimen demonstrated promising antitumor activity and well acceptable toxicity in metastatic pancreatic cancer. Further randomized controlled studies will be required in a larger patient population. Clinical trial information: NCT05327582. Research Sponsor: None.|expressing solid tumors, liver transaminases # 2 x ULN, bilirubin WNL, ECOG PS 0-1. selectively targeting VEGF receptors (VEGFR) 1, 2, and 3, FGFR 1, and CSF-1R. Recent BNT321 given on Qwk, Q2wk, and Q4wk schedules. Lead in dose (1 mg/kg given 1 wk prior to studies showed that small molecule anti-vascular inhibitor combined with a PD-1 inhibitor assigned dose) evaluated on Q2wk + Q4wk schedules. BNT321 + mFFX given Q2wk as 1L or exhibited encouraging efficacy in PDAC. This study is to assess the efficacy and safety of 2L metastatic therapy (1L+2L met). Dexamethasone given as premedication. Endpoints: surufatinib plus sintilimab (an anti-PD-1 antibody),nab-paclitaxel and gemcitabine(AG) as safety, MTD, RP2D, efficacy, PK, changes in serum CA19-9. Results: 82 pts received first-line therapy for mPDAC pts. Here we report the preliminary results. BNT321 monotherapy and 15 received BNT321 + mFFX. BNT321 monotherapy MTD was 2 Methods: Eligible pts $18 years old with histologically confirmed mPDAC, ECOG PS 0-1, mg/kg Q2wk and MTD with mFFX was 1 mg/kg. Schedule and lead in dose did not sig-nificantly alter MTD. Dose limiting toxicities (DLTs) for BNT321 monotherapy and with mFFX were elevations in hepatic AST and ALT with or without bilirubin elevations. These events with at least one measurable lesion were enrolled. Pts received surufatinib (250mg, orally daily), sintilimab (200mg, I.V., D1, Q3W), nab-paclitaxel (125mg/m 2 , I.V., D1, D8, Q3W) and gemcitabine (1000mg/m 2 ,I.V.,D1, D8, Q3W). Based on Simon's Two-stage design, 11 generally occurred early (cycle 1), resolved with drug hold, and did not preclude subsequent patients would be enrolled in stage 1; if 3 or more responses were observed, the trial would reduced dose BNT321. Frequent related AEs (total %/ . grade 3 %) for BNT321 include continue to stage 2, and additional 21 patients would be enrolled. The total sample size increased ALT (39%/19%), AST (35%/12%), T bilirubin (27%/9%), fatigue (21%/0%), infusion was 32. The primary endpoint was objective response rate (ORR). Secondary endpoints related reaction (IRR) (17%/1%) and for BNT321 + mFFX fatigue (67%/0%), increased AST (40%/27%), ALT (33%/20%), diarrhea (33%/0%), nausea (20%/0%). At combination MTD (n=7): fatigue (71%/0%), diarrhea (29%/0%), IRR (29%/0%), nausea (28%/0%), increased AST (14%/14%), ALT (14%/14%). BNT321 demonstrated a T 1/2 of 11.75 days + dose proportional Cmax and AUC with intra-patient variability. Enhanced clearance observed among pts with higher baseline (BL) serum CA19-9. For BNT321 monotherapy stable disease (RECIST 1.1) was best response, with time on study . 90 days and . 180 days in . 20% and 10% of pts, respectively. Correlation between time on study and post BL normalization of CA19-9 was observed. For BNT321 + mFFX (1L+2L met), PRs were observed in 3/11 (27%) response included progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. Results: At cutoff date of Aug 25, 2023, 15 pts were enrolled and received at least one time treatment. Median age was 60 years (range 45-68), male 53.3%, ECOG PS 1 100%, 66.7% of pts had more than 3 sites of metastasis. The most common metastatic sites were lymph nodes (66.7%) and liver (60.0%). 12 pts had received at least one tumor assessment. Six out of 11 evaluable pts responded during stage 1, allowing for enrollment to continue with a planned 21 additional patients in stage 2. Eight pts achieved partial response (PR), 3 pts achieved stable disease (SD), and the confirmed ORR (c-ORR) was 50.0% (6/12) (95% confidence interval [CI]: 21.1-78.9), and the DCR was 91.7% (11/12)|expressing solid tumors, liver transaminases # 2 x ULN, bilirubin WNL, ECOG PS 0-1. selectively targeting VEGF receptors (VEGFR) 1, 2, and 3, FGFR 1, and CSF-1R. Recent BNT321 given on Qwk, Q2wk, and Q4wk schedules. Lead in dose (1 mg/kg given 1 wk prior to studies showed that small molecule anti-vascular inhibitor combined with a PD-1 inhibitor assigned dose) evaluated on Q2wk + Q4wk schedules. BNT321 + mFFX given Q2wk as 1L or exhibited encouraging efficacy in PDAC. This study is to assess the efficacy and safety of 2L metastatic therapy (1L+2L met). Dexamethasone given as premedication. Endpoints: surufatinib plus sintilimab (an anti-PD-1 antibody),nab-paclitaxel and gemcitabine(AG) as safety, MTD, RP2D, efficacy, PK, changes in serum CA19-9. Results: 82 pts received first-line therapy for mPDAC pts. Here we report the preliminary results. BNT321 monotherapy and 15 received BNT321 + mFFX. BNT321 monotherapy MTD was 2 Methods: Eligible pts $18 years old with histologically confirmed mPDAC, ECOG PS 0-1, mg/kg Q2wk and MTD with mFFX was 1 mg/kg. Schedule and lead in dose did not sig-nificantly alter MTD. Dose limiting toxicities (DLTs) for BNT321 monotherapy and with mFFX were elevations in hepatic AST and ALT with or without bilirubin elevations. These events with at least one measurable lesion were enrolled. Pts received surufatinib (250mg, orally daily), sintilimab (200mg, I.V., D1, Q3W), nab-paclitaxel (125mg/m 2 , I.V., D1, D8, Q3W) and gemcitabine (1000mg/m 2 ,I.V.,D1, D8, Q3W). Based on Simon's Two-stage design, 11 generally occurred early (cycle 1), resolved with drug hold, and did not preclude subsequent patients would be enrolled in stage 1; if 3 or more responses were observed, the trial would reduced dose BNT321. Frequent related AEs (total %/ . grade 3 %) for BNT321 include continue to stage 2, and additional 21 patients would be enrolled. The total sample size increased ALT (39%/19%), AST (35%/12%), T bilirubin (27%/9%), fatigue (21%/0%), infusion was 32. The primary endpoint was objective response rate (ORR). Secondary endpoints related reaction (IRR) (17%/1%) and for BNT321 + mFFX fatigue (67%/0%), increased AST (40%/27%), ALT (33%/20%), diarrhea (33%/0%), nausea (20%/0%). At combination MTD (n=7): fatigue (71%/0%), diarrhea (29%/0%), IRR (29%/0%), nausea (28%/0%), increased AST (14%/14%), ALT (14%/14%). BNT321 demonstrated a T 1/2 of 11.75 days + dose proportional Cmax and AUC with intra-patient variability. Enhanced clearance observed among pts with higher baseline (BL) serum CA19-9. For BNT321 monotherapy stable disease (RECIST 1.1) was best response, with time on study . 90 days and . 180 days in . 20% and 10% of pts, respectively. Correlation between time on study and post BL normalization of CA19-9 was observed. For BNT321 + mFFX (1L+2L met), PRs were observed in 3/11 (27%) response included progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. Results: At cutoff date of Aug 25, 2023, 15 pts were enrolled and received at least one time treatment. Median age was 60 years (range 45-68), male 53.3%, ECOG PS 1 100%, 66.7% of pts had more than 3 sites of metastasis. The most common metastatic sites were lymph nodes (66.7%) and liver (60.0%). 12 pts had received at least one tumor assessment. Six out of 11 evaluable pts responded during stage 1, allowing for enrollment to continue with a planned 21 additional patients in stage 2. Eight pts achieved partial response (PR), 3 pts achieved stable disease (SD), and the confirmed ORR (c-ORR) was 50.0% (6/12) (95% confidence interval [CI]: 21.1-78.9), and the DCR was 91.7% (11/12)|expressing solid tumors, liver transaminases # 2 x ULN, bilirubin WNL, ECOG PS 0-1. selectively targeting VEGF receptors (VEGFR) 1, 2, and 3, FGFR 1, and CSF-1R. Recent BNT321 given on Qwk, Q2wk, and Q4wk schedules. Lead in dose (1 mg/kg given 1 wk prior to studies showed that small molecule anti-vascular inhibitor combined with a PD-1 inhibitor assigned dose) evaluated on Q2wk + Q4wk schedules. BNT321 + mFFX given Q2wk as 1L or exhibited encouraging efficacy in PDAC. This study is to assess the efficacy and safety of 2L metastatic therapy (1L+2L met). Dexamethasone given as premedication. Endpoints: surufatinib plus sintilimab (an anti-PD-1 antibody),nab-paclitaxel and gemcitabine(AG) as safety, MTD, RP2D, efficacy, PK, changes in serum CA19-9. Results: 82 pts received first-line therapy for mPDAC pts. Here we report the preliminary results. BNT321 monotherapy and 15 received BNT321 + mFFX. BNT321 monotherapy MTD was 2 Methods: Eligible pts $18 years old with histologically confirmed mPDAC, ECOG PS 0-1, mg/kg Q2wk and MTD with mFFX was 1 mg/kg. Schedule and lead in dose did not sig-nificantly alter MTD. Dose limiting toxicities (DLTs) for BNT321 monotherapy and with mFFX were elevations in hepatic AST and ALT with or without bilirubin elevations. These events with at least one measurable lesion were enrolled. Pts received surufatinib (250mg, orally daily), sintilimab (200mg, I.V., D1, Q3W), nab-paclitaxel (125mg/m 2 , I.V., D1, D8, Q3W) and gemcitabine (1000mg/m 2 ,I.V.,D1, D8, Q3W). Based on Simon's Two-stage design, 11 generally occurred early (cycle 1), resolved with drug hold, and did not preclude subsequent patients would be enrolled in stage 1; if 3 or more responses were observed, the trial would reduced dose BNT321. Frequent related AEs (total %/ . grade 3 %) for BNT321 include continue to stage 2, and additional 21 patients would be enrolled. The total sample size increased ALT (39%/19%), AST (35%/12%), T bilirubin (27%/9%), fatigue (21%/0%), infusion was 32. The primary endpoint was objective response rate (ORR). Secondary endpoints related reaction (IRR) (17%/1%) and for BNT321 + mFFX fatigue (67%/0%), increased AST (40%/27%), ALT (33%/20%), diarrhea (33%/0%), nausea (20%/0%). At combination MTD (n=7): fatigue (71%/0%), diarrhea (29%/0%), IRR (29%/0%), nausea (28%/0%), increased AST (14%/14%), ALT (14%/14%). BNT321 demonstrated a T 1/2 of 11.75 days + dose proportional Cmax and AUC with intra-patient variability. Enhanced clearance observed among pts with higher baseline (BL) serum CA19-9. For BNT321 monotherapy stable disease (RECIST 1.1) was best response, with time on study . 90 days and . 180 days in . 20% and 10% of pts, respectively. Correlation between time on study and post BL normalization of CA19-9 was observed. For BNT321 + mFFX (1L+2L met), PRs were observed in 3/11 (27%) response included progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. Results: At cutoff date of Aug 25, 2023, 15 pts were enrolled and received at least one time treatment. Median age was 60 years (range 45-68), male 53.3%, ECOG PS 1 100%, 66.7% of pts had more than 3 sites of metastasis. The most common metastatic sites were lymph nodes (66.7%) and liver (60.0%). 12 pts had received at least one tumor assessment. Six out of 11 evaluable pts responded during stage 1, allowing for enrollment to continue with a planned 21 additional patients in stage 2. Eight pts achieved partial response (PR), 3 pts achieved stable disease (SD), and the confirmed ORR (c-ORR) was 50.0% (6/12) (95% confidence interval [CI]: 21.1-78.9), and the DCR was 91.7% (11/12)|expressing solid tumors, liver transaminases # 2 x ULN, bilirubin WNL, ECOG PS 0-1. selectively targeting VEGF receptors (VEGFR) 1, 2, and 3, FGFR 1, and CSF-1R. Recent BNT321 given on Qwk, Q2wk, and Q4wk schedules. Lead in dose (1 mg/kg given 1 wk prior to studies showed that small molecule anti-vascular inhibitor combined with a PD-1 inhibitor assigned dose) evaluated on Q2wk + Q4wk schedules. BNT321 + mFFX given Q2wk as 1L or exhibited encouraging efficacy in PDAC. This study is to assess the efficacy and safety of 2L metastatic therapy (1L+2L met). Dexamethasone given as premedication. Endpoints: surufatinib plus sintilimab (an anti-PD-1 antibody),nab-paclitaxel and gemcitabine(AG) as safety, MTD, RP2D, efficacy, PK, changes in serum CA19-9. Results: 82 pts received first-line therapy for mPDAC pts. Here we report the preliminary results. BNT321 monotherapy and 15 received BNT321 + mFFX. BNT321 monotherapy MTD was 2 Methods: Eligible pts $18 years old with histologically confirmed mPDAC, ECOG PS 0-1, mg/kg Q2wk and MTD with mFFX was 1 mg/kg. Schedule and lead in dose did not sig-nificantly alter MTD. Dose limiting toxicities (DLTs) for BNT321 monotherapy and with mFFX were elevations in hepatic AST and ALT with or without bilirubin elevations. These events with at least one measurable lesion were enrolled. Pts received surufatinib (250mg, orally daily), sintilimab (200mg, I.V., D1, Q3W), nab-paclitaxel (125mg/m 2 , I.V., D1, D8, Q3W) and gemcitabine (1000mg/m 2 ,I.V.,D1, D8, Q3W). Based on Simon's Two-stage design, 11 generally occurred early (cycle 1), resolved with drug hold, and did not preclude subsequent patients would be enrolled in stage 1; if 3 or more responses were observed, the trial would reduced dose BNT321. Frequent related AEs (total %/ . grade 3 %) for BNT321 include continue to stage 2, and additional 21 patients would be enrolled. The total sample size increased ALT (39%/19%), AST (35%/12%), T bilirubin (27%/9%), fatigue (21%/0%), infusion was 32. The primary endpoint was objective response rate (ORR). Secondary endpoints related reaction (IRR) (17%/1%) and for BNT321 + mFFX fatigue (67%/0%), increased AST (40%/27%), ALT (33%/20%), diarrhea (33%/0%), nausea (20%/0%). At combination MTD (n=7): fatigue (71%/0%), diarrhea (29%/0%), IRR (29%/0%), nausea (28%/0%), increased AST (14%/14%), ALT (14%/14%). BNT321 demonstrated a T 1/2 of 11.75 days + dose proportional Cmax and AUC with intra-patient variability. Enhanced clearance observed among pts with higher baseline (BL) serum CA19-9. For BNT321 monotherapy stable disease (RECIST 1.1) was best response, with time on study . 90 days and . 180 days in . 20% and 10% of pts, respectively. Correlation between time on study and post BL normalization of CA19-9 was observed. For BNT321 + mFFX (1L+2L met), PRs were observed in 3/11 (27%) response included progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. Results: At cutoff date of Aug 25, 2023, 15 pts were enrolled and received at least one time treatment. Median age was 60 years (range 45-68), male 53.3%, ECOG PS 1 100%, 66.7% of pts had more than 3 sites of metastasis. The most common metastatic sites were lymph nodes (66.7%) and liver (60.0%). 12 pts had received at least one tumor assessment. Six out of 11 evaluable pts responded during stage 1, allowing for enrollment to continue with a planned 21 additional patients in stage 2. Eight pts achieved partial response (PR), 3 pts achieved stable disease (SD), and the confirmed ORR (c-ORR) was 50.0% (6/12) (95% confidence interval [CI]: 21.1-78.9), and the DCR was 91.7% (11/12)|expressing solid tumors, liver transaminases # 2 x ULN, bilirubin WNL, ECOG PS 0-1. selectively targeting VEGF receptors (VEGFR) 1, 2, and 3, FGFR 1, and CSF-1R. Recent BNT321 given on Qwk, Q2wk, and Q4wk schedules. Lead in dose (1 mg/kg given 1 wk prior to studies showed that small molecule anti-vascular inhibitor combined with a PD-1 inhibitor assigned dose) evaluated on Q2wk + Q4wk schedules. BNT321 + mFFX given Q2wk as 1L or exhibited encouraging efficacy in PDAC. This study is to assess the efficacy and safety of 2L metastatic therapy (1L+2L met). Dexamethasone given as premedication. Endpoints: surufatinib plus sintilimab (an anti-PD-1 antibody),nab-paclitaxel and gemcitabine(AG) as safety, MTD, RP2D, efficacy, PK, changes in serum CA19-9. Results: 82 pts received first-line therapy for mPDAC pts. Here we report the preliminary results. BNT321 monotherapy and 15 received BNT321 + mFFX. BNT321 monotherapy MTD was 2 Methods: Eligible pts $18 years old with histologically confirmed mPDAC, ECOG PS 0-1, mg/kg Q2wk and MTD with mFFX was 1 mg/kg. Schedule and lead in dose did not sig-nificantly alter MTD. Dose limiting toxicities (DLTs) for BNT321 monotherapy and with mFFX were elevations in hepatic AST and ALT with or without bilirubin elevations. These events with at least one measurable lesion were enrolled. Pts received surufatinib (250mg, orally daily), sintilimab (200mg, I.V., D1, Q3W), nab-paclitaxel (125mg/m 2 , I.V., D1, D8, Q3W) and gemcitabine (1000mg/m 2 ,I.V.,D1, D8, Q3W). Based on Simon's Two-stage design, 11 generally occurred early (cycle 1), resolved with drug hold, and did not preclude subsequent patients would be enrolled in stage 1; if 3 or more responses were observed, the trial would reduced dose BNT321. Frequent related AEs (total %/ . grade 3 %) for BNT321 include continue to stage 2, and additional 21 patients would be enrolled. The total sample size increased ALT (39%/19%), AST (35%/12%), T bilirubin (27%/9%), fatigue (21%/0%), infusion was 32. The primary endpoint was objective response rate (ORR). Secondary endpoints related reaction (IRR) (17%/1%) and for BNT321 + mFFX fatigue (67%/0%), increased AST (40%/27%), ALT (33%/20%), diarrhea (33%/0%), nausea (20%/0%). At combination MTD (n=7): fatigue (71%/0%), diarrhea (29%/0%), IRR (29%/0%), nausea (28%/0%), increased AST (14%/14%), ALT (14%/14%). BNT321 demonstrated a T 1/2 of 11.75 days + dose proportional Cmax and AUC with intra-patient variability. Enhanced clearance observed among pts with higher baseline (BL) serum CA19-9. For BNT321 monotherapy stable disease (RECIST 1.1) was best response, with time on study . 90 days and . 180 days in . 20% and 10% of pts, respectively. Correlation between time on study and post BL normalization of CA19-9 was observed. For BNT321 + mFFX (1L+2L met), PRs were observed in 3/11 (27%) response included progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. Results: At cutoff date of Aug 25, 2023, 15 pts were enrolled and received at least one time treatment. Median age was 60 years (range 45-68), male 53.3%, ECOG PS 1 100%, 66.7% of pts had more than 3 sites of metastasis. The most common metastatic sites were lymph nodes (66.7%) and liver (60.0%). 12 pts had received at least one tumor assessment. Six out of 11 evaluable pts responded during stage 1, allowing for enrollment to continue with a planned 21 additional patients in stage 2. Eight pts achieved partial response (PR), 3 pts achieved stable disease (SD), and the confirmed ORR (c-ORR) was 50.0% (6/12) (95% confidence interval [CI]: 21.1-78.9), and the DCR was 91.7% (11/12)|expressing solid tumors, liver transaminases # 2 x ULN, bilirubin WNL, ECOG PS 0-1. selectively targeting VEGF receptors (VEGFR) 1, 2, and 3, FGFR 1, and CSF-1R. Recent BNT321 given on Qwk, Q2wk, and Q4wk schedules. Lead in dose (1 mg/kg given 1 wk prior to studies showed that small molecule anti-vascular inhibitor combined with a PD-1 inhibitor assigned dose) evaluated on Q2wk + Q4wk schedules. BNT321 + mFFX given Q2wk as 1L or exhibited encouraging efficacy in PDAC. This study is to assess the efficacy and safety of 2L metastatic therapy (1L+2L met). Dexamethasone given as premedication. Endpoints: surufatinib plus sintilimab (an anti-PD-1 antibody),nab-paclitaxel and gemcitabine(AG) as safety, MTD, RP2D, efficacy, PK, changes in serum CA19-9. Results: 82 pts received first-line therapy for mPDAC pts. Here we report the preliminary results. BNT321 monotherapy and 15 received BNT321 + mFFX. BNT321 monotherapy MTD was 2 Methods: Eligible pts $18 years old with histologically confirmed mPDAC, ECOG PS 0-1, mg/kg Q2wk and MTD with mFFX was 1 mg/kg. Schedule and lead in dose did not sig-nificantly alter MTD. Dose limiting toxicities (DLTs) for BNT321 monotherapy and with mFFX were elevations in hepatic AST and ALT with or without bilirubin elevations. These events with at least one measurable lesion were enrolled. Pts received surufatinib (250mg, orally daily), sintilimab (200mg, I.V., D1, Q3W), nab-paclitaxel (125mg/m 2 , I.V., D1, D8, Q3W) and gemcitabine (1000mg/m 2 ,I.V.,D1, D8, Q3W). Based on Simon's Two-stage design, 11 generally occurred early (cycle 1), resolved with drug hold, and did not preclude subsequent patients would be enrolled in stage 1; if 3 or more responses were observed, the trial would reduced dose BNT321. Frequent related AEs (total %/ . grade 3 %) for BNT321 include continue to stage 2, and additional 21 patients would be enrolled. The total sample size increased ALT (39%/19%), AST (35%/12%), T bilirubin (27%/9%), fatigue (21%/0%), infusion was 32. The primary endpoint was objective response rate (ORR). Secondary endpoints related reaction (IRR) (17%/1%) and for BNT321 + mFFX fatigue (67%/0%), increased AST (40%/27%), ALT (33%/20%), diarrhea (33%/0%), nausea (20%/0%). At combination MTD (n=7): fatigue (71%/0%), diarrhea (29%/0%), IRR (29%/0%), nausea (28%/0%), increased AST (14%/14%), ALT (14%/14%). BNT321 demonstrated a T 1/2 of 11.75 days + dose proportional Cmax and AUC with intra-patient variability. Enhanced clearance observed among pts with higher baseline (BL) serum CA19-9. For BNT321 monotherapy stable disease (RECIST 1.1) was best response, with time on study . 90 days and . 180 days in . 20% and 10% of pts, respectively. Correlation between time on study and post BL normalization of CA19-9 was observed. For BNT321 + mFFX (1L+2L met), PRs were observed in 3/11 (27%) response included progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. Results: At cutoff date of Aug 25, 2023, 15 pts were enrolled and received at least one time treatment. Median age was 60 years (range 45-68), male 53.3%, ECOG PS 1 100%, 66.7% of pts had more than 3 sites of metastasis. The most common metastatic sites were lymph nodes (66.7%) and liver (60.0%). 12 pts had received at least one tumor assessment. Six out of 11 evaluable pts responded during stage 1, allowing for enrollment to continue with a planned 21 additional patients in stage 2. Eight pts achieved partial response (PR), 3 pts achieved stable disease (SD), and the confirmed ORR (c-ORR) was 50.0% (6/12) (95% confidence interval [CI]: 21.1-78.9), and the DCR was 91.7% (11/12)|

|Grade 4 neutropenia was observed in six patients, grade 3 neutropenia in 10 (29.4%), anemia in four (11.8%), diarrhea in two (5.9%), and malaise, lung infection, peripheral sensory neuropathy, colitis, and biliary tract infection in one (2.9%) each. Twenty-two patients required dose reduction, mainly because of neutropenia. Mean RDIs at the sixth course of oxaliplatin, irinotecan, leucovorin, acute infusion of fluorouracil, and con-tinuous infusion of fluorouracil were 77.0%, 88.2%, 81.8%, 84.4%, and 87.6%, respec-tively. ORR, median PFS, and median OS were 44.1%, 15.8 months, and 25.8 months, respectively. Conclusions: Postoperative complications following neoadjuvant therapy and surgery in a phase 2 borderline resectable pancreatic cancer clinical trial (Alliance A021501). Methods: The A021501 phase 2 trial randomized patients with borderline resectable pancreatic ductal ade-nocarcinoma to 8 doses of mFOLFIRINOX (Arm 1) or 7 doses of mFOLFIRINOX then hypofractionated radiotherapy (Arm 2), followed by pancreatectomy (Dec 31, 2016-Jan 1, 2019). Patients underwent resection according to defined operative standards at enrolling centers without specific requirements for either surgeon or hospital volume. Surgical complications and adverse events were assessed and captured at a single time point of 90 days after surgery and compared between treatment arms. Results: Of 126 enrolled patients, 51 (40%) underwent pancreatectomy (n=32, Arm 1; n=19, Arm 2) at 28 institutions. Vascular resection was performed in 19 patients (37%). One patient in Arm 2 died within 90 days after surgery. Rates of any surgical complication were 19% (n=6) in Arm 1 and 42% (n=8) in Arm 2 (p=0.07). Median length of stay was 7 days (range 5-38 days). Five (10%) patients required reoperation within 90 days. Readmission rates were higher in Arm 2 than Arm 1 (16% vs. 42%, p=0.04) but there were no differences in rates of reoperation, pancreatic fistula or abscess requiring drainage, or wound infection between study arms. 54% of patients (n=26/48) experienced a grade 3 or higher adverse event, with no difference between treatment arms (47% versus 67%, p=0.7). Rates of initiation of adjuvant therapy did not differ between treatment arms (66% vs. 68%, p=0.4). Pancreatic fistula and abscess were associated with adjuvant therapy (p,0.01). No difference in overall survival was observed based on occurrence of surgical com-plications (HR 1.1; 95% CI 0.5-2.6). Conclusions: Clinical trial information: NCT02839343. Research Sponsor: NIHU10CA180821; NIHU10CA180882; NIHU10CA180868; NIHU10CA180888; NIH.| |---|

|669|Poster Session| |---|---|

|667|Poster Session|

|Paclitaxel protein bound (A) plus gemcitabine (G) plus cisplatin (C) and|Paclitaxel protein bound (A) plus gemcitabine (G) plus cisplatin (C) and|

|hydroxychloroquine (HCQ) neoadjuvant therapy for localized pancreatic|hydroxychloroquine (HCQ) neoadjuvant therapy for localized pancreatic|

|ductal adenocarcinoma (PDAC). First Author: Erkut Hasan Borazanci,|ductal adenocarcinoma (PDAC). First Author: Erkut Hasan Borazanci,|

|HonorHealth Research Institute, Scottsdale, AZ||

|Background: Neoadjuvant therapy has become the consensus treatment for individuals|Background: Neoadjuvant therapy has become the consensus treatment for individuals|

|with locally advanced (LA) and borderline resectable (BR) PDAC. Neoadjuvant therapy|with locally advanced (LA) and borderline resectable (BR) PDAC. Neoadjuvant therapy|

|for resectable (R) PDAC has been in greater use due to concerns over micro metastases|for resectable (R) PDAC has been in greater use due to concerns over micro metastases|

|at diagnosis. Typical therapies involve the use of multiagent systemic chemotherapy|at diagnosis. Typical therapies involve the use of multiagent systemic chemotherapy|

|with or without radiation therapy. In retrospective studies, Cancer Antigen 19-9 (CA 19-9)|with or without radiation therapy. In retrospective studies, Cancer Antigen 19-9 (CA 19-9)|

|normalization in borderline resectable (BR) and locally advanced (LA) PDAC has been|normalization in borderline resectable (BR) and locally advanced (LA) PDAC has been|

|associated with greater OS. The addition of cisplatin (C) to gemcitabine (G) and|associated with greater OS. The addition of cisplatin (C) to gemcitabine (G) and|

|paclitaxel protein bound (A), has shown promising clinical data in a previously reported|paclitaxel protein bound (A), has shown promising clinical data in a previously reported|

|study in advanced PDAC [JAMA Oncol. 2020;6(1):125-132]. HCQ has been shown to|study in advanced PDAC [JAMA Oncol. 2020;6(1):125-132]. HCQ has been shown to|

|target autophagy in PDAC and has demonstrated higher response in combination with|target autophagy in PDAC and has demonstrated higher response in combination with|

|GA. We conducted a prospective, phase 2 clinical trial of patients with R, BR, and LA|GA. We conducted a prospective, phase 2 clinical trial of patients with R, BR, and LA|

|PDAC utilizing a regimen combining A + G + C + HCQ with the primary endpoint of CA 19-|PDAC utilizing a regimen combining A + G + C + HCQ with the primary endpoint of CA 19-|

|9 normalization (NCT04669197). Methods: Eligibility criteria include patients with|9 normalization (NCT04669197). Methods: Eligibility criteria include patients with|

|histologically confirmed R, BR, or LA PDAC, elevated CA 19-9, and a KPS $ 70% with|histologically confirmed R, BR, or LA PDAC, elevated CA 19-9, and a KPS $ 70% with|

|normal end organ function. Doses are A 125 mg/m2, G 1000 mg/m2, C 25 mg/ m2 on|normal end organ function. Doses are A 125 mg/m2, G 1000 mg/m2, C 25 mg/ m2 on|

|days 1, 8 of a 21-day cycle (IV) along with HCQ 600 mg po bid. Primary objective is to|days 1, 8 of a 21-day cycle (IV) along with HCQ 600 mg po bid. Primary objective is to|

|evaluate CA 19-9 normalization with the neoadjuvant chemotherapy. Secondary ob-|evaluate CA 19-9 normalization with the neoadjuvant chemotherapy. Secondary ob-|

|jectives are to assess R0 rate, pathologic complete response (pCR), safety and tol-|jectives are to assess R0 rate, pathologic complete response (pCR), safety and tol-|

|erability, radiologic response rate (by RECIST 1.1), and 2 year overall survival (OS) from|erability, radiologic response rate (by RECIST 1.1), and 2 year overall survival (OS) from|

|date of study entry. Exploratory objectives include evaluating imaging biomarkers and|date of study entry. Exploratory objectives include evaluating imaging biomarkers and|

|vascular involvement by tumor in relation to therapy. Results: To date all planned 12|vascular involvement by tumor in relation to therapy. Results: To date all planned 12|

|patients have been enrolled, 11 evaluable. 8 male, 4 female; age range 50 to 76 yo.|patients have been enrolled, 11 evaluable. 8 male, 4 female; age range 50 to 76 yo.|

|Patient classifications is 3 R; 4 BR; 5 LAPC. Most common drug related grade (gr) 3-4|Patient classifications is 3 R; 4 BR; 5 LAPC. Most common drug related grade (gr) 3-4|

|adverse events (AEs) are: thrombocytopenia gr 3 27%, gr 4 27%, anemia gr 3 36%, and|adverse events (AEs) are: thrombocytopenia gr 3 27%, gr 4 27%, anemia gr 3 36%, and|

|neuropath gr 3 36%. CA 19-9 normalization occurred in 36% (4/11) who have completed|neuropath gr 3 36%. CA 19-9 normalization occurred in 36% (4/11) who have completed|

|at least 1 cycle of treatment. To date, 3 individuals went to surgery, with 3 achieving R0.|at least 1 cycle of treatment. To date, 3 individuals went to surgery, with 3 achieving R0.|

|Among 56 patients who completed the 4 cycle of FOLFIRINOX plus HIFU and continued chemotherapy, partial response was achieved in 36 patients (60.0%, 36/60), and stable disease in 20 patients. Regarding the adverse effect (AE), 32 of 60 patients experienced grade 3 (n=22) or grade 4 (n=10) AE, all of them aged $ 75 years with pathologically proven unresectable pancreatic adenocarcinoma were enrolled after obtaining written informed consent. Patients were treated with a modified regimen of gemcitabine (1000 mg/m 2 ) and nab-paclitaxel (125 mg/m 2 ) on days 1, 15 of every 28-day cycle. The primary endpoint was the overall response rate. Secondary endpoints included disease control rate, overall survival, progression-free survival, 1-year survival rate, 2-year survival rate, and adverse events. Results: From August 2018 to March 2021, 17 patients were enrolled (locally advanced 4; metastatic 13). Five patients (29.4%) were men, and the median age was 77 years (range: 75-81). The median Geriatric 8 score was 13 points (range 6-17). Biliary drainage was performed in three patients. The overall response rate was 47.1% (8/17). Disease control rate was 82.4% (14/17). Median overall survival was 16.8 months (95% confidence interval (CI) 5.9-24.6) and median progression-free survival was 8.3 months (95% CI: 4.9-10.1), respectively. Grade 3 or 4 hematologic adverse events and non-hematologic adverse events were observed in 17.6% (3/17) and 29.4% (5/17), respectively. No deaths was observed in association with biweekly GnP regimen. Conclusions: Biweekly GnP as first-line therapy can provide favorable treatment outcomes with tolerable toxicity in older adult patients with unresectable PC. Clinical trial information: jRCTs051190038. Research Sponsor: None. January 2010 and March 2023 with SBRT 30-50 Gy in 3-5 fractions or CFRT 50-60 Gy in 25-30 fractions. We excluded all patients with resectable disease who underwent surgery. Clinicopathological data, treatment regimens, and radiation parameters were collected and analyzed. Results: A total of 51 patients (17 females, 34 males; median age: 67.9 years). 24 patients (47.1%) were treated with CFRT, and 27 patients (52.9%) were treated with SBRT. Median time of follow-up for the entire cohort was 14.4 months. A total of 13 patients (25%) experienced a Local failure (LF) at a median time of 18.5 months, with no difference observed between CFRT and SBRT groups. Cancer-specific mortality (CSM) was statistically significant with a lower mortality rate in SBRT (37%) vs CFRT group (63%) (p,0.004). 678 671 Updated results of a phase 1b/2 study of surufatinib plus camrelizumab, Poster Session nab-paclitaxel and S-1 (NASCA) as first-line therapy for metastatic pancre-atic adenocarcinoma (mPDAC). First Author: Ru Jia, Senior Department of On-cology, The 5th Medical Center of the PLA General Hospital, Beijing, China Background: This prospective, randomized controlled phase 1b/2 clinical study was designed to explore the efficacy and safety of surufatinib combined with camrelizumab, nab-paclitaxel and S-1 as first-line treatment compared with nab-paclitaxel and gemcitabine (AG) in mPDAC. Preliminary data was reported (Guanghai Dai, 2023 ASCO, 4142). Here we presented the updated data as more patients (pts) were recruited. Methods: In phase 1b, pts with mPDAC received surufatinib (200mg to 300mg, qd po), camrelizumab (200mg, I.V., D1, Q3W), nab-paclitaxel (125mg/m 2 , I.V., D1, D8, Q3W), and S-1 (40mg bid, D1-14, Q3W). Phase 2 is a prospective, open-label, randomized (1:1) trial comparing NASCA with AG in the first-line setting. The primary objective was the RP2D and overall response rate (ORR) per RECIST v1.1. Tumor tissue samples were collected at diagnosis and were subjected to mIHC to evaluate tumor immune microenvironment. Results: From Aug 2021 to Jun 2023, 49 pts were enrolled. As previously reported, 6 pts were enrolled in phase 1b and RP2D was determined as surufatinib 200mg. Of the 49 pts, 48 were evaluable for efficacy (28 in NASCA and 20 in AG group). ORR was 53.6% (15/28) (95% CI: 35.8-70.5) in pts receiving NASCA (pts in phase 1b included) and 15.0% (3/20) (95% CI: 5.2-36.0) in AG group. In NASCA group, pts with liver metastases exhibited higher ORR than those without liver metastases (71.4% vs 35.7%, p=0.13). Median progression-free survival and overall survival was 9.17m (95% CI: 5.5-NA) and 15.57m (95% CI: 9.27-NA) in NASCA group, 6.3m (95% CI: 4.87-NA) and 8.63m (95% CI: 7.90-NA) in AG group at the median follow-up of 13.7m. The most frequent adverse events (AEs) of all-grade in NASCA were neutropenia (57.1%), hepatotoxicity (42.9%), and neuropathy (39.3%). Immune-related AEs were observed in 5 pts with grade 3 hepatotoxicity in 4 pts and grade 2 enteritis in 1 pt. Safety was comparable in two groups except for hepatotoxicity and diarrhea. Using mIHC, the tissue of 13 pts treated with NASCA were stained for multiple markers of immune cells. CD3 + T cells infiltrated the tumor core at the highest level, followed by CD68 + CD163 -(M1) macrophages, and FOXP3 + T cells. Majority of immune cells and ICI biomarkers were expressed at higher proportion in the stroma. Pts with liver metastases displayed elevated tumoral FOXP3 + T cells (p=0.031), PD-L1 + CD68 + Poster Session Significant prognostic factors for the overall subject population were ECOG PS (HR 1.80, p=0.019), liver metastasis (HR 2.36, p,0.01), CRP (HR 1.91, p,0.01) and NLR (HR 2.65, p,0.01). The only significant prognostic factor in the elderly was liver metastasis (HR macrophages (p=0.014), and decreased infiltration of stromal CD8 Patients respectively. The 1-year survival rate and 2-year survival rates were 58.8% and 29.4%, 2.59, p,0.01). Conclusions:| |---|

|Methods: A 5-mm thick section of Formalin-Fixed Paraffin-Embedded (FFPE) tissue from a retrospective cohort of 28 PDAC cases were analyzed using the Precision Immunooncology panel (PIP, HTG Molecular Diagnostics) on a NextSeq 550 sequencer (Illumina). The RNA expression of 1392 immune-related genes were analyzed. Principal Components (PC) and Manhattan distance were studied for data visualization and clustering. Maxstat algorithm (maxstat v0.7-25) was used to establish optimal cut-offs for variable categorization. Log-rank and Cox regression were used for both univariate and multivariate for survival. All tests were two-tailed. The statistical analysis was performed using R studio (R version 4.0.3). Lastly, immuno-histochemistry (IHC) for CD4, CD8, CD20, PD1, PD-L1, and LAG-3 proteins was performed on tissue microarrays (TMAs) to assess their correlation with RNA expression. Results: Unsupervised analysis of the gene expression identified two clusters of pa-tients with differentially prognostic information. These two groups were defined with a logistic regression model of 14 genes (BTLA, CXCR5, DLX6, KLHDC9, KRT13, LAG3, LGSN, MICB, SIGLEC5, SPINK5, SPN, TBX21, UPK2, ZIC5) showing for cluster1 and cluster 2 a median survival of 13 (0-97.583) and 57 (0.67-256.08) months, respectively (p-value = 0.0088). 682|Poster Session| |---|---|

|686|Poster Session| |---|---|

||Methods: We performed a single-institution ret-|

|rospective analysis of BRPC, LAPC, and medically inoperable PDAC patients to evaluate|rospective analysis of BRPC, LAPC, and medically inoperable PDAC patients to evaluate|

|ALC values 1 month before vs. 1-3 months after A-RT. All were treated with 5-fraction A-|ALC values 1 month before vs. 1-3 months after A-RT. All were treated with 5-fraction A-|

|RT on a 0.35 T MR-Linac; the spleen was not considered an organ-at-risk during|RT on a 0.35 T MR-Linac; the spleen was not considered an organ-at-risk during|

|treatment planning. Lymphopenia was assessed using CTCAE version 5.0. Results: 101|treatment planning. Lymphopenia was assessed using CTCAE version 5.0. Results: 101|

|patients were evaluated with median age 71 years (range 35-94 years), median max-|patients were evaluated with median age 71 years (range 35-94 years), median max-|

|imum tumor size of 3.6 cm (range, 1.3-6.8 cm), and frequently tumor in the pancreas|imum tumor size of 3.6 cm (range, 1.3-6.8 cm), and frequently tumor in the pancreas|

|head (84.2%). Most had LAPC (61.4%) followed by BRPC (28.7%). Induction chemo-|head (84.2%). Most had LAPC (61.4%) followed by BRPC (28.7%). Induction chemo-|

|therapy (ICT) was routine (89.1%), most commonly FOLFIRINOX (61.4%) with a median|therapy (ICT) was routine (89.1%), most commonly FOLFIRINOX (61.4%) with a median|

|ICT duration of 5.2 months (range, 0.2-14.0 months). Median prescribed dose was 50 Gy|ICT duration of 5.2 months (range, 0.2-14.0 months). Median prescribed dose was 50 Gy|

|(range, 40-50 Gy). The median mean spleen dose was 2.75 Gy (range, 0.38-16.79 Gy).|(range, 40-50 Gy). The median mean spleen dose was 2.75 Gy (range, 0.38-16.79 Gy).|

|First Author: Cody Eslinger, Department of Internal Medicine, Mayo Clinic Arizona, Phoenix, AZ Background: PACC is a rare malignancy originating from the exocrine pancreas, ac-counting for less than 1% of all pancreatic cancers. Due to the rarity of the disease entity, there is a paucity of data to guide treatment decisions. This retrospective study aims to provide additional clinical characteristics and outcomes to aid in future treatment decisions. Methods: Pathology records from Mayo Clinic (AZ, FL, MN) patients (pts) denoting acinar or mixed-acinar cell carcinoma were searched between 2002 to 2023 and selected for retrospective review. Pt demographics, treatment courses, and next generation sequencing (NGS) were collected. Results: A total of 62 pts (74% male, n = 46) were identified with median age 64 years old. Histologic subtypes were 67% pure acinar cell carcinoma (42/62), 24% mixed acinar-neuroendocrine (15/62), and 8% mixed acinar-adenocarcinoma (5/62). AJCC stages at diagnosis were 34% stage I/II (21/62), 16% stage III (10/62), and 50% stage IV (31/62). Early-stage disease was treated with upfront surgical resection (81%, 17/21). Locally advanced disease received neoadjuvant therapy (NAT) followed by surgical resection (80%, 8/10). FOLFIRINOX was most often chosen as NAT (65%, 11/17), while others received gemcitabine-based NAT. The R0 resection rate was 86%. The 3 and 5-year survival estimates for stage III were 90.9% (95% CI: 75.4 -100%) and 67.3% (95% CI: 42.3 -100%), respectively. The 3 and 5-year survival estimates for stage IV were 36.6% (95% CI: 18.6 -71.9%) and 29.3% (95% CI: 13.1 -65.5%), respectively. Median survival time for stage IV was 3 years. Somatic NGS testing was done in 24 pts with alterations found in: homologous recombination (HR) in 42% (10/24); RAF alterations in 25% (6/24); mismatch repair (MMR) in 13% (3/24; none of them with MMR germline mutations), 1 ETV6-NTRK3 fusion, and 1 FGFR mutation. Germline NGS testing was done in 21 pts and alterations in HR were seen in 33% (7/21) of pts. This led to additional therapeutic options in 46% (11/24) of pts. Poster Session Mucin 5 AC (MUC5AC) to predict pathologic treatment response (TR) to neoadjuvant chemotherapy (NAT) in resected-pancreatic ductal adenocar-cinoma (R-PDA). Analysis of variance (ANOVA), t-tests, and Wilcoxon tests were used for statistical analysis. Results: Tissue samples from 100 R-PDA (43 received NAT and 57 had upfront surgery (UpS)) were available for testing. The median age of diagnosis was 65 years, and p=0.012). Conclusions: 690 induced cytidine deaminase, was present in 18/434 (4.1%) samples, and was signifi-cantly associated with improved OS in the overall study population (log-rank p=6.5e-4, FDR-adjusted-p=0.026). SBS93, a signature of unknown etiology previously seen in other gastrointestinal cancers, was present in 4/434 (0.9%) samples, and was significantly associated with worse OS in the overall study population (log-rank, p=7e-6; FDR-adjusted-p=1.1e-3). SBS33, also of unknown etiology and previously seen in other gastrointestinal cancers, was present in 73/434 (16.8%) samples. It was seen more frequently in advanced disease (Fisher's-exact p=1.9e-4), but was significantly asso-ciated with worse OS only in the resected cohort (log-rank, p=2.3e-4, FDR-adjusted-50% were females. MM and IM were positive in 96% R-PDA (MM-95% Ap and 72% EC).In the NAT group, 89% (n=38) had 5-fluorouracil (5FU) based (36 FOLFIRINOX and 2 FOLFOX), and the rest received gemcitabine (Gem)-based therapy; patients received a median of 6 cycles of NAT; 37% (16) had preoperative chemoradiation (CRT) after NAT; 63% (27) had adjuvant systemic therapy (AST); pathologic objective response (OR = near complete or partial) and no response (NR) to NAT was reported in 63% (27) and 37% (16), respectively. In UpS group, 92% and 4% had AST (48 Gem-based, 4 5FU-based) and adjuvant CRT, respectively. The median time to recurrence (mTTR) and overall survival of the group was 15 and 33 months (m), respectively. NAT group had significantly (p,0.05) lower EC-positive MM (mean H-score 108 vs. 151), IM (mean H-score 122 vs. 162), and mTTR (11 vs 15 m) than Study Population OR vs. NR vs. UpS Mean H-score (p-value) mTTR in m (p-value) MM IM Any NAT (n=100) 113 vs. 154 vs. 164 (0.06) 104 vs 152 vs 162 (0.01) 12 vs. 7.5 vs. 15 (0.001) FOLFIRINOX NAT only (n=93) 110 vs 153 vs 164 (0.05) 105 vs. 149 vs. 163 (0.03) 12 vs. 8.5 vs. 15 (0.01) 691 Poster Session Genomics and transcriptomics of pancreatic adenosquamous carcinoma. First Author: Brooke Elizabeth Kania, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ Background: Pancreatic cancer (PC) is anticipated to become the 2nd leading cause of cancer-related deaths by 2030. Pancreatic adenosquamous carcinoma (PASC) is a rare subtype of PC with histology including squamous adenomatous features ($30% squamous histology), while pancreatic squamous cell cancer (PSCC) consists purely of squamous cells. We evaluated genomic, transcriptomic and prognostic differences between PASC, PSCC and pancreatic ductal adenocarcinoma (PDAC). Methods: 8951 PC Conclusions: FDR correction. SBS85, a signature associated with indirect effects of activation-tumors (83 PASC, 22 PSCC & 8846 PDAC) tested at Caris Life Sciences with WTS (Illumina, Novaseq) and| |---|

||694|||Poster Session|| |---|---|---|---|---|---|

||Association between TP53 gain of function and loss of function mutational|||||

||subgroups and survival in pancreatic adenocarcinoma. First Author: Nitzan|||||

||Zohar, Thomas Jefferson University, Philadelphia, PA|Zohar, Thomas Jefferson University, Philadelphia, PA|Zohar, Thomas Jefferson University, Philadelphia, PA|Zohar, Thomas Jefferson University, Philadelphia, PA||

||Background: TP53 is a commonly mutated tumor suppressor in pancreatic adenocar-|||||

||cinoma (PDAC) but the clinical implications for different classes of TP53 variants remain|||||

||unclear. In contrast to loss of function (LOF) mutations, TP53 gain of function (GOF)|||||

||mutations alter DNA conformational binding (e.g. R175H, G245S, R249S, R282H) or|||||

||modify DNA contact hotspots (e.g. R248Q, R248W, R273H) and are associated with|||||

||aggressive phenotypes. Here, we analyze progression-free survival (PFS) on standard|||||

||therapies and overall survival (OS) of PDAC patients (pts) within TP53 mutational|||||

||subgroups: GOF, LOF, and wild type (WT). Methods: We analyzed longitudinal outcomes|||||

||across 775 pts with next generation DNA sequencing (NGS) results from Perthera's Real-|||||

||World Evidence database who received at least 1 line of therapy in the advanced setting|||||

||for PDAC. PFS was evaluated from initiation of 1st line for advanced disease until|||||

||discontinuation. Hazard ratios and p-values were computed via Cox regression when|||||

||comparing OS relative to date of advanced diagnosis and PFS on subsets who received|||||

||1st line FOLFIRINOX (FFX) or 1st line gemcitabine/nab-paclitaxel (GA). Differences in|||||

||frequencies of genomic alterations between TP53 mutational subgroups were analyzed|||||

||by Fisher's exact test. Results: In the TP53 LOF subgroup, median PFS on 1st line GA was|||||

||significantly worse than 1st line FFX (Table) but this difference was not observed in TP53|||||

||GOF or WT subgroups. Irrespective of 1st line therapy choice, median OS in the WT|||||

||subgroup (2.1y [1.8-2.4]) was significantly longer (p,0.05) than pts with TP53 GOF (1.5y|||||

||[1.3-2.1]) or TP53 LOF (1.4y [1.3-1.5] ). KRAS mutations were enriched (unadjusted|||||

||p,0.05) for co-occurrence with TP53 in GOF (93.7%) and LOF (93.3%) subgroups relative|||||

||to WT (74.5%). Mutations in BRCA1/2 were less common in the TP53 GOF subgroup|||||

||(2.5%) relative to LOF (5.Mutational Subgroup|mPFS [95% CI]|mPFS [95% CI]|FFX vs GA||

||(N=775, %)||on 1st line FFX (# pts)|on 1st line GA (# pts)|p-value (HR [95% CI])|

||TP53 GOF (n=134, 17%)||9.5m [7.5-13.3] (n=77)|8.4m [7.5-13.4] (n=57)|0.5337 (1.16 [0.73-1.85]|

||TP53 LOF (n=436, 56%)|9.0m [7.1-10.3] (n=230)|6.1m [5.6-7.1] (n=206)|0.0001171 (0.61 [0.48-0.79])||

||TP53 WT (n=205, 27%)||9.2m [7.1-13] (n=112)|9.1m [8.3-11.2] (n=93)|0.7088 (0.93 [0.65-1.34] )|

|695|Poster Session|||||

|Utility of circulating tumor DNA (ctDNA) for the detection of minimal residual||||||

|disease (MRD) after curative-intent therapy for patients with localized||||||

|pancreatic adenocarcinoma (PDAC): A single institution series and meta-||||||

|analysis. First Author: Ujwal R. Yanala, Division of Surgical Oncology, Department of||||||

|Surgery, University of Miami Miller School of Medicine, Miami, FL||||||

|Background:||||||

|||||698|||Poster Session| |---|---|---|---|---|---|---|---|

|KRASm TP53m CDKN2Am SMAD4m KRASm imbalances|LAPC (n=37) 0 31 (84%) 28 (76%) 21 (57%)|Metastatic (n=231) 207 (90%) 189 (82%) 148 (64%) 102 (45%)|P-value 0.08 .0.99 0.26 0.21|Comparisons Outcomes or Molecular Comparison|Wnt Pathway MUT Median [95% CI] (# Pts) or Frequency (%)|Wnt Pathway WT Median [95% CI] (# Pts) or Frequency (%)|MUT vs WT P-value (HR [95% CI])|

|Balanced Minor Major Median SNVs Median Indel burden Median SVs|25 (68%) 12 (32%) 0 4892 440 60|82 (39%) 83 (40%) 45 (21%) 5709 564 77|0.0008 0.009 0.006 0.008|mOS (years since advanced diagnosis) mPFS (months on 1st line GA) mPFS (months on 1st line FFX) KRAS Mutation TP53 Mutation PIK3CA Mutation|2.0y [1.6-2.4] (72) 11.2m [8.9-N/A] (36) 12.2m [11.7-N/A] (36) 79.3% 59.9% 5.7%|1.5y [1.4-1.7] (702) 7.1m [6.1-7.7] (320) 8.9m [7.5-10] (382) 89.6% 75.9% 1.7%|0.0258 (0.69 [0.5-0.96]) 0.00407 (0.51 [0.33-0.81] ) 0.0646 (0.63 [0.38-1.03]) 0.0000223 0.000527 0.00045|

|m=mutation.||||MSI-High|3.5%|0.9%|0.00378|

|699||Poster Session||||||

|Characterization of the cachexia pathway in pancreatic ductal||||||||

|adenocarcinoma. First Author: Karam Ashouri, Norris Comprehensive Cancer Cen-||||||||

|ter, Keck School of Medicine, University of Southern California, Los Angeles, CA||||||||

|Background: Cancer cachexia is characterized by progressive weight loss and skeletal||||||||

|muscle degradation, contributing to 33% of pancreatic ductal adenocarcinoma (PDAC)||||||||

|deaths. Targeting myostatin in the myostatin-activin pathway has been shown to reverse||||||||

|cachexia. Here, we present comprehensive clinical and molecular characterization of the||||||||

|myostatin-activin pathway in PDAC. Methods: 9,607 samples of PDAC tested at Caris Life||||||||

|Sciences (Phoenix, AZ) with WTS (Illumina NovaSeq) and NextGen DNA sequencing||||||||

|(NextSeq, 592 Genes and NovaSEQ, WES) were analyzed. Cachexia gene scores (GS||||||||

|Biomarker|Expert CCC|Novice CCC|p-value|C-index, OS| |---|---|---|---|---|

|RECIST|0.77 [0.59-0.88]|0.26 [-0.17-0.61]|0.008|0.50 [0.45-0.55]|

|DVSeg|0.52 [0.22-0.73]|-0.05 [-0.43-0.34]|0.021|0.55 [0.55-0.56]|

|DVReg|0.95 [0.90-0.98]|0.83 [0.67-0.91]|0.012|0.58 [0.56-0.60]|

|DBSeg|0.08 [-0.28-0.41]|0.13 [-0.50-0.67]|0.893|0.62 [0.57-0.66]|

|DBReg|0.93 [0.86-0.97]|0.70 [0.48-0.84]|0.002|0.64 [0.62-0.66]|

||||||706||Poster Session| |---|---|---|---|---|---|---|---|

|Characteristics of Patients with Pancreatic Cancer|Without Diabetes|With Diabetes||||||

|Total Patients|106,106 (95% CI, 102822-|44,169 (95% CI, 42673-||||||

||109387)||45666)|||||

|Percentage (%)|71%||29%|||||

|Age (years)|68 (95% CI, 68.00-68.37)|68 (95% CI, 68.12-68.57)||||||

|Sex||||||||

|-Women|51%|p,0.01|53%|p,0.01||||

|-Men|49%|p,0.01|47%|p,0.01||||

|Ethnicity||||||||

|-Whites -Blacks|70% 13%||64% 15%|p,0.01|Multivariate analysis (RS and clinical features).|||

|-Hispanics -Asians|7% 10%||10% 11%||Variable|Hazard Ratio (95% CI)|p|

|Insurance Status -Medicare -Medicaid -Private Insurance -Other|60% 9% 29% 2%||63% 9% 26% 2%|p,0.01|RS-High Age Vessel involvement Pancreatic head tumor Sex_male|2.895 (1.760-4.761) 1.027 (1.006-1.049) 2.289 (0.939-7.700) 1.479 (0.910-2,404) 1.413 (0.881-2.266)|,0.001** 0.013* 0.065 0.114 0.151|

|707|||Poster Session|||||

||Hazard|95% Confidence||| |---|---|---|---|---|

|Parameter|Ratio|Limits||p-value|

|LO group vs EL group|1.315|1.258|1.375|,.0001|

|IL group vs EL group|1.692|1.607|1.782|,.0001|

|Black vs White|1.103|1.058|1.151|,.0001|

|Female vs Male|0.955|0.930|0.982|0.0011|

|Hispanic vs Non-Hispanic|0.983|0.942|1.025|0.4197|

|Chemotherapy or Not|2.614|2.535|2.695|,.0001|

|Metropolitan vs Non-metropolitan|0.968|0.919|1.019|0.2122|

|OTHER GI CANCER||181s| |---|---|---|

|IHC Stain|Cases Tested (%)|Cases Positive (%)|

|CK7|70|81|

|CK20|65|7|

|MOC-31|26|0|

|Ber-EP4|4|0|

|Calretinin|35|50|

|WT-1|39|56|

|D2-40|13|0|

|CK5/6|35|25|

||Any Grade|Grade 3 or Higher| |---|---|---|

|irAE|(n/%)|(n/%)|

||||746||Poster Session|Poster Session| |---|---|---|---|---|---|---|

|||||Overall N=52|Pancreatic N=13|Colorectal N=13|

||||ORR by IRC, % (95% CI)|44.2 (30.5, 58.7)|53.8 (25.1, 80.8)|30.8 (9.1, 61.4)|

||||Median lines of prior therapy (range)|2.0 (0-9)|2.0 (1-4)|3.0 (2-9)|

||||Complete response, n (%)|3 (5.8)|1 (7.7)|0 (0.0)|

||||Partial response, n (%)|20 (38.5)|6 (46.2)|4 (30.8)|

||||Stable disease ‡16 weeks, n (%)|12 (23.1)|2 (15.4)|6 (46.2)|

||||Median PFS, months (95% CI)|13.2 (5.6, 26.2)|5.6 (3.2, NE)|9.1 (4.0, 17.0)|

|Dasatinib Dose Estimated response probability Estimated toxicity probability|100 mg (95% CI) 38% (3.9% to 82.5%) 9% (0% to 33.4%)|140 mg (95% CI) 50% (12.4 to 87.9%) 14% (0.4% to 45.7%)|Median f/u, month Median DoR, months (95% CI) Median f/u, months|24.8 (11.0, 33.2) 37.2 (13.3, NE) 28.6 (11.2, 40.9)|16.4 (11.0, 33.2) 52.1 (2.5, NE) 18.9 (7.4, 31.3)|24.8 (7.1, 24.8) 13.3 (5.6, NE) 11.2 (6.5, NE)|

|757|Poster Session| |---|---|

|Cancer types represented||

|Esophagogastric||

|HCC||

|Biliary||

|Pancreatic Adenocarcinoma||

|Colorectal||

|Small Intestine||

|GIST||

|||Grants,|Funding amount|| |---|---|---|---|---|

|||n (%)|(in millions), $||

|Fiscal year|2018|353 (24.8)|154.5||

||2019|345 (24.2)|147.2||

||2020|364 (25.5)|165.7||

||2021|364 (25.5)|159.2||

|Gender|Male|1035 (72.6)|450.6||

||Female|391 (27.4)|175.9||

|Cancer|Pancreatic and liver|788 (55.3)|339.5||

||Colorectal|528 (37.0)|235.9||

||Others (gastric, esophageal,|110 (7.7)|51.2||

||anal, cholangiocarcinoma)||||

||||761|Poster Session|

Comparison of screening rates LEP vs. non-LEP.

The higher risk was associated with differences in tumor stage at diagnosis, tumor factors, and treatment factors. Targeted interventions to improve CRC symptom awareness and remove barriers to CRC diagnosis and treatment among vulnerable populations may be needed to eliminate disparities in early-onset CRC survival. Research Sponsor: Genentech. Race and ethnicity with risk of death among individuals with EOCRC.

Characteristics of patients with LS by ASA/NSAID use/non-use.

Patients with localized AA who undergo surgical resection have a low risk of relapse, especially those with goblet AA. This retrospective analysis did not identify a benefit from adjuvant chemotherapy. Considering the clear histologic and molecular differences between AA and CRC, these data call into question the current practice of applying CRC data to guide AC decisions in AA. Prospective clinical trials of AC in AA, stratified by histologic subtype, are urgently needed. Research Sponsor: None.

age at consent was 67.4 years (range 31 -92). 44% were female. 214/451 (47%) had a prior positive fecal occult blood test (FOBT). Of individuals with a negative or unknown FOBT testing, 161/237 (68%) had GI symptoms (e.g. abdominal pain, bloody/narrowing stool, constipation/diarrhea). The test identified 88% (268/305) of CRCs, including 71% (79/111) Stage I, 98% (87/89) Stage II, 97% (90/93) Stage III, and 100% (12/12) Stage IV. Overall sensitivity in detecting Stage I-III was 87%. The test identified 37% (54/146) of AAs, including 49% (33/68) of carcinoma in situs and 24% (9/37) of AAs with high-grade dysplasia. Sensitivity for right-sided CRC was 84% (61/73), 87% (59/68) for left-sided CRC, and 90% (148/164) for rectal tumors. Stage I test sensitivity was significantly associated with tumor size (.20mm; p,0.01), left-sided or rectal tumor location (p,0.05), and tumor depth (p,0.01) in univariate analysis, whereas the tumor depth (T2) was the sole factor associated with test positivity (p,0.05) in multivariate analysis. Specificity on this assay is 90% as determined in the ECLIPSE clinical study (NCT04136002

Results: Compared to FIT screening at age 50, FIT screening at 45 reduced deaths by 5,220, incidence by 11,980, and added 96,100 health-adjusted life years (HALY). Colonoscopy screening at age 45 led to 17,870 fewer deaths, 74,250 fewer cases and added 314,960 HALYs. FIT and colonoscopy screening at age 45 had incremental costs of CAD$3,259 and $7,881 per HALY gained vs. a FIT at age 50, respectively. Across screening strategies, the greatest benefits were observed in the youngest cohort. Colonoscopy screening at age 45 resulted in 10,679,540 more total colonoscopies than the current capacity of 8,966,979 with FIT screening at age 50. Lowering the screening age to 45 with a FIT increased colonoscopy demand by 329,555. The total cost of CRC care (screening, diagnosis and treatment) increased with lower screening ages and colonoscopy first modalities, while the cost of CRC management (diagnosis and treatment) decreased with lower screening ages and colonoscopy first approaches. Conclusions: Adjusting current CRC screening guidelines demonstrates significant resource implications with proportional health benefits. Lower screening ages and colonoscopy first approaches have the largest resource demand and greatest health outcomes, while the incremental cost per HALY gained for all screening strategies is modest compared to standard benchmarks. Research Sponsor: None.

Patient perceptions about clinical trials.

). Within the 3 mos group, 226 (97%) received CAPOX. Within the 6 mos group, there was a 51%/49% split between CAPOX/FOLFOX. By univariate analysis, factors associated with 3 mos of CAPOX vs 6 mos of ACT were age .70y (P=0.039), low/intermediate grade (P=0.005) and low-risk stage III disease (P,0.0001). 29% of pts planned for 6 mos of oxaliplatin ACT had low-risk disease, with 52% of these receiving CAPOX. Conclusions: 3 mos of adjuvant CAPOX is an accepted option for nearly all pts with stage III disease with consequent less neurotoxicity and fewer treatment visits. Yet, in this contemporary cohort, use of 3 mos of adjuvant CAPOX remains low and is associated with older age and low-risk disease. 6 mos of oxaliplatin is still being offered to pts with low-risk disease. Exploration of patient preferences, real-world treatment and time toxicities, and resource costs may improve more widespread adoption of 3 mos of adjuvant CAPOX in stage III CRC. Research Sponsor: None.

Efficacy and safety of LY3537982, a potent and highly selective KRAS G12C inhibitor in KRAS G12C-mutant GI cancers: Results from a phase 1 study. First Author: Antoine Hollebecque, Gustave Roussy, Villejuif, France Background: LY3537982 is an oral, potent, and highly selective inhibitor of GDP-bound KRAS G12C with unique pharmacologic properties that achieve high target occupancy at low absolute exposures. Here we present results of GI tumors treated on LOXO-RAS-20001, a phase 1 study of LY3537982 in patients (pts) with a KRAS G12C mutation. Methods: Dose escalation followed a mTPI-2 method. Dose expansion included a combination with cetuximab in colorectal cancer (CRC). All pts were KRAS G12C inhibitor naïve. Key objectives were to determine the RP2D, safety, PK, and antitumor activity per RECIST v1.1. Results: As of 24 July 2023, 73 pts with CRC (32),

Table shows efficacy data. Conclusions: In pts with GI tumors, LY3537982 alone or in combination with cetuximab demonstrated preliminary efficacy and a favorable safety profile. Clinical trial information: NCT04956640. Research Sponsor: Loxo Oncology, Inc. on behalf of Eli Lilly and Company.

Fruquintinib with PD-1 inhibitors versus TAS-102 with bevacizumab in lateline mCRC: A retrospective cohort study based on propensity score matching. First Author: Rongrong Li, Department of Medical Oncology Gastroenterology and Urology, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China Background: Fruquintinib with PD-1 inhibitors (FP) and TAS-102 with bevacizumab (TB) are two common therapies for patients with previous-treated metastatic colorectal cancer (mCRC). However, it's still not clear that which therapy can bring better prognosis. Methods: This is a retrospective cohort study conducted in Hunan Cancer Hospital. Patients (pts) with mCRC who had received at least the 2 nd line treatment were eligible. Propensity score (PS) would be calculated to balance the baseline characteristics of two arms. Overall survival (OS) was set as the primary endpoint.

Among pts alive at the data cutoff (n = 31), 30 remained treatment-free after initial study treatment without receiving any subsequent systemic therapy, with a median treatment-free interval of 34.7 mo (range, 1.6-61.4mo).Exploratory analysis by tumor mutational burden status will be presented.Safety data are shown in the Table.Conclusions: At 64-mo follow-up, NIVO + IPI continued to demonstrate clinically meaningful survival and durable responses, with mPFS, mOS, and mDOR still not reached, suggesting the potential for long-term clinical benefit. Safety remained consistent with previous data. These findings further support current recommendations for NIVO + IPI as a 1L treatment for pts with MSI-H/dMMR mCRC. Clinical trial information: NCT02060188. Research Sponsor: Bristol Myers Squibb.

The ORR was 12.5% and 21.1%, with median duration of response of 14.0 months and not reached, respectively.In an exploratory analysis of the overall population, pts with esophageal cancer had the highest ORR of 33.First Author: Kodai Takemori, Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan Background: As treatment for unresectable advanced/recurrent colorectal cancer (ARCC), the introduction of doublet chemotherapy, represented by FOLFOX/FOLFIRI, and molecular-targeting agents, such as anti-VEGF antibody and anti-EGFR antibody, has given ARCC patients a more than three years' survival.Triplet chemotherapy, such as FOLFOXIRI 6 Bevacizumab or Panitumumab, has already been used in daily practice.Real-world analysis of irinotecan (iri) with or without fluorouracil (5FU) in the second line treatment (2L) of metastatic colorectal cancer (mCRC). First Author: Robert William Lentz, University of Colorado Cancer Center, Aurora, CO Background: The most used 1 st line (1L) chemotherapy backbone for mCRC is fluoropyrimidine (FP) + oxaliplatin. In the 2L, iri alone or with 5FU (FOLFIRI), 6 a biologic agent (biologic), are options. It is unclear whether adding 5FU to iri is beneficial following disease progression on prior FP. Methods: This study used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database to identify patients diagnosed with mCRC from 01-01-2013 to 02-13-2023, who received 1L with FP + oxaliplatin 6 biologic, and 2L with irinotecan 6 5FU 6 biologic. Baseline patient/tumor characteristics were obtained.

Prospective observational study investigating the impact of treatment sequence using regorafenib and FTD/TPI for metastatic colorectal cancer on overall survival (OSERO study). First Author: Akihiko Chida, Department of Internal Medicine, Division of Gastroenterology and Hepatology, Keio University School of Medicine, Shinjuku-Ku, Japan Background: Regorafenib (REG) and trifluridine/tipiracil (FTD/TPI) with or without bevacizumab (BEV) are widely used as a later-line treatment for patients (pts) with metastatic colorectal cancer (mCRC). It is still unclear which is the preferable treatment strategy to start with, either REG, FTD/TPI, or FTD/TPI + BEV in clinical practice.

Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study. First Author: Kathleen J Yost, Cancer Research Consortium of West Michigan, Grand Rapids, MI Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with specific genomic alterations. Results in a cohort of pts with CRC with BRCA1/2 mut treated with Tala are reported. Methods: Eligible pts had measurable disease, ECOG performance status (PS) 0-2, adequate organ function, and no standard treatment (tx) options. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received 1 mg of Tala orally daily until disease progression. Primary endpoint was disease control (DC) per investigator defined as complete or partial response or stable disease of at least 16 weeks (wks) duration (SD16+) per RECIST v 1.1. Simon 2-stage design tested the null DC rate of 15% vs. 35% (power = 0.85; a = 0.10). If $2 of 10 pts in stage 1 have DC, 18 more pts are enrolled; otherwise, the cohort is closed. If $7 of 28 pts have DC, the null DC rate is rejected. Secondary endpoints were objective response (OR), progression-free survival (PFS), overall survival (OS), and safety.

Table summarizes pt demographics and outcomes.No pts experienced DC, median PFS was 8 wks (95% CI, 6 to 8) and median OS was 24 wks (95% CI, 7 to 43).Co-alterations were observed in the following genes: KRAS (3 pts) and BRAF (2 pts). 2 pts had 3 separate grade 3 adverse events of anemia or fatigue at least possibly related to Tala.Conclusions: Monotherapy Tala did not demonstrate sufficient clinical activity in pts with advanced CRC with BRCA1/2 mut.Other tx should be considered for these pts, including tx offered in clinical trials.Clinical trial information: NCT02693535.Research Sponsor: Pfizer; AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Genentech, Merck, Seagen, Taiho Oncology.An ARCAD database nomogram for prognostic prediction of treatment refractory metastatic colorectal cancer.First Author: Eiji Oki, Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University Hospital, Fukuoka, Japan Background: The "No Placebo Initiative" demonstrated that the survivals of patients (pts) receiving placebo in a salvage-line setting, exhibited no significant difference across trials (CORRECT, RECOURSE, CONCUR and TERRA).Therefore, we believe that a nomogram can be generated using the ARCAD database to predict survival of pts who completed standard therapy.Methods: Of 40,889 Individual patient data (IPD) from 59 studies, 723 pts received placebo from 4 randomized studies were pooled.The potential prognostic factors considered include BMI and Age.Imputed datasets were constructed by a multiple imputation method since the original dataset contains some missing values.Overall survival (OS) was defined as the time from randomization to death from any cause.Multivariate Cox proportional hazards models for OS were estimated based on the variables showing clinically and statistically significant by univariate analysis.Prediction performance of the final model was evaluated using the concordance index for survival data and calibration plots.Results: From univariate and multivariate analysis, ECOG performance status, Royal Marsden Hospital score (calculated by albumin level, LDH level, and number of metastatic site), primary site location, liver meta, peritoneal meta were selected as variables.We successfully developed a highly accurate nomogram to predict post-standard treatment prognosis for pts with mCRC.Concordance index for OS was 0.66.Conclusions: Although further validation in other cohorts is needed, this nomogram could be very useful to estimate the survival for clinical practice and enrolling in clinical trials.Research Sponsor: ARCAD Asia.It is a retrospective, observational study.The clinical, surgical, and pathological characteristics were investigated retrospectively and statistical analyses were performed using chi-square test, independent samples T-test, and Kaplan-Meier analysis.Mid TCC was defined as tumor arising in the middle third of transverse colon and determined by intraoperative exploration.Hepatic and splenic flexure colon cancer, which were defined as tumor is adjacent to liver or spleen, were excluded.Radical resection was conducted along the embryological surgical plane, following D2 or D3 dissection.Central vessel ligation was defined as ligation of root of middle colic artery.Real-world evidence of FOLFIRI combined with anti-angiogenesis inhibitors or anti-EGFR antibodies for patients with early recurrence colorectal cancer after adjuvant FOLFOX/CAPOX therapy in Japan: A retrospective observational study using administrative database. First Author: Yu Sunakawa, Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan Background: Oxaliplatin-containing regimens (FOLFOX or CAPOX) are the most common adjuvant treatments after curative resection of colorectal cancer (CRC). However, real-world evidence (RWE) of treatment sequence/outcomes for patients with early recurrence CRC after receiving adjuvant chemotherapy are limited. Methods: This retrospective cohort study was based on an administrative database in Japan. The primary objective was to describe the treatment sequence for patients with early recurrence CRC and treated by

Relationship between fluoropyrimidine (FPD) exposure and outcomes in patients with metastatic colorectal cancer (mCRC) receiving trifluridine/ tipiracil (FTD/TPI) with or without bevacizumab (BEV) in the phase 3 SUN-LIGHT trial. First Author: Marwan Fakih, Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA

First Author: Hideaki Bando, Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan Background: Randomized clinical trials provide the best evidence for the effects of a new treatment.However, the use of a placebo control arm may present practical and ethical concerns for enrolled patients and treating providers.The CRC ARCAD global database includes a total of 1,673 individual patient data (IPD) treated with placebo plus best supportive care in a salvage-line setting for refractory mCRC.By using placebo IPD, we have proposed to construct a synthetic control arm for clinical trials(Yoshino T. et al., Nature Medicine 2023). Methods: From 40,889 IPD from 59 studies in ARCAD mCRC database, 723 placebo pts were selected from 4 placebo-controlled randomized studies in a salvage-line setting (CORRECT, RECOURSE, CONCUR and TERRA). We analyzed the impact of baseline patient characteristics and various prognostic factors on outcome in the placebo control. Number of metastatic sites, ECOG PS, liver metastasis, peritoneal metastasis and RMH Score were significant prognostic factors in patients with mCRC receiving placebo in a salvage-line setting. Further prognostic factors should be investigated to increase the accuracy of the proposed synthetic control arm. Research Sponsor: ARCAD foundation.

This study is an open-label, multicenter, phase III trial conducted in Colorectal Cancer Study Group of Japan Clinical Oncology Group. We randomly assigned, in a 1:1 ratio, patients who were refractory or intolerant to fluoropyrimidine, oxaliplatin, irinotecan, angiogenesis inhibitor, anti-EGFR antibody (if RAS-wild type), BRAF inhibitor and anti-EGFR antibody (if BRAF V600E -mutant), and immune check point inhibitor (if dMMR/MSI-H) to the treatment of mCRC to receive 4-week intervals FTD/TPI 70mg/m 2 /day monotherapy (arm A) or bi-weekly FTD/TPI plus bevacizumab 5mg/kg (arm B). The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), response rate (RR), disease control rate (DCR), and safety. Results: In consideration of the results of the SUNLIGHT trial, this study was prematurely terminated. Between January 2022 and February 2023, a total of 152 patients were randomized (75 in the arm A and 77 in the arm B). Patient backgrounds between the two arms were well balanced. At the data cut-off date, all enrolled patients discontinued protocol treatment due to disease progression (69.3% vs. 59.7%) and Initial efficacy evaluation of fruquintinib plus capecitabine versus capecitabine as maintenance treatment for metastatic colorectal cancer (mCRC): A randomized, controlled, phase Ib/II study. First Author: Wenhua Li, Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China Background: The standard first-line therapy followed by maintenance treatment is an optional approach to balance the efficacy and toxicity for mCRC. Fruquintinib (Fru), a highly specific inhibitor of VEGFR1/2/3, has demonstrated favorable safety and efficacy outcomes in the treatment of mCRC. In this study, we present findings from an investigation into the comparative efficacy and safety of Fru in combination with capecitabine (Cap) versus Cap as a maintenance therapy for patients (pts) with mCRC.

TAS-102 plus anti-EGFR re-challenge group. Research Sponsor: National Taiwan University Hospital Hsinchu Branch; Ministry of Health and Welfare (Taiwan). Short-course nivo-ipi is very effective in locally advanced dMMR rectal cancer and may become an alternative to resection. Clinical trial information: 2022-500646-14-00. Research Sponsor: Odense University Hospital.

Total neoadjuvant therapy (TnT) with FOLFOX followed by short course radiation in locally advanced rectal cancer: A phase II study. First Author: Janice Zhao, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY Background: Total neoadjuvant therapy (TnT) is a new standard-of-care for locally advanced rectal cancer (LARC). Few prospective studies have evaluated specifically the use of chemotherapy and short course radiation (SCRT) in obtaining a complete clinical response (cCR)

Preliminary efficacy and safety of fruquintinib as maintenance therapy after first-line treatment in metastatic colorectal cancer (mCRC): A multicenter, randomized, open-label clinical trial (the FRONT study). First Author: Xiaojing Xu, Department of Oncology, Cancer center, Zhongshan Hospital, Fudan University, Shanghai, China Background: Maintenance therapy and discontinuation of treatment are options to mCRC patients who response to first-line treatment. We conducted this study to evaluate the efficacy and safety of fruquintinib as maintenance therapy after first-line treatment for mCRC. Methods: This is an ongoing, multicenter, open-label, randomized clinical trial. Patients (pts) with unresectable right-sided mCRC or RAS-mutant left-sided mCRC, who hadn't suffer disease progression after first-line standard treatment (chemotherapy with or without bevacizumab) for four to six months, were eligible. MSS) colorectal cancer (CRC). First Author: Daneng Li, City of Hope Comprehensive Cancer Center, Los Angeles, CA Background: ADG126 is a fully human anti-CTLA-4 IgG1 SAFEbody that has a cleavable masking peptide that blocks the antigen binding site. ADG126 is preferentially activated in the tumor microenvironment to afford prolonged on-tumor drug exposure and limited offtumor toxicity. Activated ADG126 binds to a unique CTLA-4 epitope to prime T cells via partial ligand blockade and deplete immunosuppressive Tregs through strong antibody-

Subgroup analyses of the phase 3 CAIRO3 trial: Association of number and total volume of metastases on survival in patients with metastatic colorectal cancer based on a deep-learning automatic segmentation model. First Author: Koen Zwart, Department of Medical Oncology, University Medical Center Utrecht, Utrecht, Netherlands

Median OS for patients with #10 versus .10metastases was 22.0 months (95%CI: 19.3-29.3)and 14.3 months (95% CI: 11.6-20.9,p-value ,0.01), with similar differences for low/high tumor volume.In multivariable analysis number and total volume were independent prognostic markers for PFS and OS, respectively, after adjustment for age, sex, WHO performance score, treatment arm, serum lactate dehydrogenase (LDH) level, site of primary tumor, time to metastases, and treatment response.Benefit of maintenance therapy was most pronounced in patients with #10 compared to .10 metastases with a PFS HR of 0.Updated survival results of ALTER-C002: Anlotinib combined with CAPEOX as first-line treatment in RAS/BRAF wild-type unresectable metastatic colorectal cancer. First Author: Yue Liu, Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China Background: Anlotinib is an oral multi-target tyrosine kinase inhibitor, mainly targeting VEGFR 1-3, FGFR 1-4, PDGFR a/b and c-kit. Previous trial had demonstrated that anlotinib monotherapy was effective and safe in advanced colorectal cancer. ALTER-C002 trial is an open-label, single-arm, phase II study, aimed to evaluate the efficacy and safety of anlotinib plus CAPEOX as first-line therapy in patients with RAS/ BRAF wildtype unresectable metastatic colorectal cancer (mCRC). The progression-free survival has been reported, preliminary results demonstrated significant antitumor activity and manageable toxicity, here we reported the overall survival results at the data cutoff of The LR+ and LR2 groups included 49 and 99 patients, respectively. No significant differences in the baseline characteristics were detected between the two groups, except liver metastasis, which occurred less frequently in the LR+ group. OS and PPS were shorter in the LR+ group compared with the LR-group (median OS,

Clinical characterization and therapeutic outcomes of patients (pts) with colorectal cancer (CRC) harboring somatic BRCA1/2 mutations.First Author: Deepak Bhamidipati, The University of Texas MD Anderson Cancer Center, Houston, TX Background: Somatic BRCA1/2 mutations in BRCA-associated cancers increase therapeutic sensitivity to platinum-based chemotherapies and PARP inhibitors, but the implications of BRCA mutations in non-BRCA-associated cancers such as CRC is unknown and hypothesized to be shaped by tumor lineage.We thus conducted a retrospective analysis of outcomes with platinum-based chemotherapy and PARP inhibition in pts with CRC, where the estimated prevalence of BRCA1/2 alterations is 3-4%.Methods: Amivantamab (ami), an EGFR-MET bispecific antibody with immune cell-directing activity, has shown preclinical activity in colorectal cancer (CRC) models.MET amplification is implicated in driving resistance to anti-EGFR therapies in metastatic CRC (mCRC).We hypothesize that dual, co-inhibition of EGFR and MET with ami could improve outcomes in relapsed/ refractory mCRC.Methods: OrigAMI-1 (NCT05379595) is assessing the safety and efficacy of ami as monotherapy in patients (pts) with refractory mCRC in 3 separate cohorts (Table).Eligible pts were wild-type for KRAS, NRAS, BRAF, and EGFR ectodomain by ctDNA testing, without ERBB2/ HER2 amplification.Cohorts A and B included pts with left-sided mCRC without/with prior ex-EML4-ALK fusion, PTEN).The most frequent treatment-emergent adverse events were rash (84%) and infusion-related reactions (53%).No new safety signals were observed.Updated results will be presented at the meeting.Conclusions: Ami monotherapy demonstrated promising, durable antitumor activity in refractory mCRC, including pts treated with prior anti-EGFR therapy and pts with right-sided disease.The safety profile of ami in mCRC is manageable and consistent with prior NSCLC experience.Clinical trial information: NCT05379595.Research Sponsor: Janssen Research & Development, LLC.Fruquintinib with PD-1 inhibitors versus fruquintinib monotherapy in lateline mCRC: A retrospective cohort study based on propensity score matching. First Author: Tianqi An, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Background: Immune checkpoint inhibitors (ICIs) are highly effective in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC). However, the population of MSI-H/dMMR only accounts for 5% of mCRC. And most of the remaining microsatellite stable or proficient mismatch repair (MSS/pMMR) mCRC patients appeared not to benefit from mere immunotherapy. Fruquintinib, as the standard third-line regimen for mCRC, is an oral small-molecule antiangiogenic tyrosine kinase inhibitor. Studies demonstrated that fruquintinib combined with programmed death receptor-1 (PD-1) inhibitors (FP) can reverse the immunosuppression and achieve promising efficacy. However, due to the lack of the research comparing the efficacy between fruquintinib monotherapy (FM) and FP, it remains unclear if FP can bring extra benefit. Methods: This is a retrospective cohort study conducted in the First Affiliated Hospital of Zhengzhou University. Patients (pts) with MSS/pMMR mCRC who had received at least the 2nd line treatment were eligible. Propensity score (PS) would be calculated to balance the baseline characteristics of two cohorts. Progression-Free survival (PFS) was set as the primary endpoint. The Kaplan-Meier method and Cox proportional hazard model was used to evaluate PFS and to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: From Apr 2020 to Jan 2023, 83 eligible pts in total were enrolled. According to the treatment received, 47 and 36 pts were respectively allocated into FP cohort and FM cohort.

ETS was defined as the relative change in the sum of the longest diameters of RECIST target lesions at first follow-up CT scan compared to baseline and DpR was defined as the relative change in the sum of the longest diameters of RECIST target lesions at the nadir in the absence of new lesions or progression of non-target lesions compared to baseline.Results: In total, 54 patients of BRAF V600E MT mCRC had at least one target lesion.In total of StageI-IV CRC patients, the incidence of BRAF V600E MT was 6.3% (233/3705).BOLD-100-001 (TRIO039): A phase 2 study of BOLD-100 in combination with FOLFOX in patients with advanced mCRC previously treated with FOLFOX/CAPOX-Efficacy and safety analysis.First Author: Jennifer L. Spratlin, Cross Cancer Institute, Edmonton, AB, Canada Background: BOLD-100 is a first-in-class metallotherapeutic with a unique multimodal mechanism of action currently in phase 2 clinical development for the treatment of advanced gastrointestinal cancers.Standard treatment options for patients (pts) with metastatic colorectal cancer (mCRC) include FOLFOX or CAPOX in first or second line therapy.This study explored the benefit of BOLD-100 + FOLFOX in previously treated mCRC patients.Methods: This prospective, phase 2 study evaluates BOLD-100 + FOLFOX in pts with mCRC.All pts received prior standard treatment, including FOLFOX or CAPOX.Pts received 625 mg/m2 of BOLD-100 + FOLFOX on day 1 of each 14-day cycle and treated until progressive disease or unacceptable toxicity.The primary objective is to evaluate PFS, OS, and ORR in treated patients.Induction chemotherapy plus concomitant oxaliplatin-based chemoradiotherapy for locally advanced rectal cancer: A real world experience at San Raffaele Hospital. First Author: Valentina Burgio, Department of Medical Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy Background: The standard treatment of locally advanced rectal cancer (LARC) consists of giving preoperative chemoradiation therapy (CT/RT) followed by surgery. Recently, total neoadjuvant therapy (TNT) has shown greater efficacy in terms of increasing the rate of complete pathological response (pCR) and reducing local and systemic relapse. However, based on the proposed therapy scheme, the risk of overtreatment and side effects is not negligible. The objective of this study was to evaluate the efficacy and safety of neoadjuvant doublet with oxaliplatin-based CT and concomitant RT.

Results of a prospective phase II study of total neoadjuvant therapy for locally advanced rectal cancer. First Author: Huiying Ma, State Key Laboratory of Molecular Oncology and Department of Radiation Oncology, National Cancer Center/ National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China Background: Total neoadjuvant therapy is further accepted for the treatment of locally advanced rectal cancer, which is more valuable for patients with high-risk factors. Optimal schedule of radiotherapy and chemotherapy remains unknown and needs further exploration. Methods: We conducted a multicenter, randomized, phase II trial Despite adjuvant chemotherapy, nearly 30% of patients with Stage III colon cancer (CC) will recur. We are performing a randomized clinical trial using a plasma-only circulating tumor DNA (ctDNA) platform after adjuvant therapy for patients with ctDNA-positive Stage III CC. Methods: Patients (pts) with Stage III CC are eligible for prescreening, including tumor tissue profiling by next-generation sequencing. Pts are screened 3-6 weeks after adjuvant chemotherapy. At screening blood is collected for ctDNA analysis with a CLIA-certified se-Secondary outcomes include RFS and OS in Arms 1 and 2, ctDNA clearance and RFS/OS in the other arms. An interim analysis is planned after 13 patients are enrolled in Arm 1 and primary outcome will be assessed after 50 patients' complete treatment/surveillance in Arms 1 and 2. Results: From 4/16/2020 through 9/8/2023, 147 patients were screened, 66 screen failed. Pre-screening as well as active ongoing enrollment is underway. To date, 73 patients have enrolled (46 male and 27 female). 53 (72.6%) were white. 10 (13.7%) patients were noted to be ctDNA+ within 6 weeks of completion of adjuvant therapy: 4 in Arm 1; 5 in Arm 2; 1 in Arm 4. 63 pts were ctDNA-and in Arm 3. Conclusions: In this ctDNA guided trial, with single time-point testing, only 13.7% of pts were ctDNA+ after adjuvant chemotherapy. 90% of ctDNA+ patients did not have an actionable biomarker. Strict windows for eligibility and enrollment initially restricted eligibility but these were adjusted to increase eligibility. To mitigate the low positivity rate and allow us to meet our accrual goals in arm 1 and 2, the protocol was amended to allow for entry into the ctDNA+ arms at any time during the first 3 years after completion of adjuvant therapy as opposed to within 6 weeks of completion of adjuvant therapy. The lessons learnt would have implications for other ctDNA-driven clinical trials. Clinical trial information: NCT03803553. Research Sponsor: Stand Up To Cancer.

Immune deconvolution revealed decreases in CD8+ T cells and neutrophils in the predicted infiltration of older males' immune cells compared to older females. Conclusions: Our research revealed that the sex of the patient is associated with the transcriptional metabolic and immune profiles in YOCRC and AOCRC. Further translational research is needed to understand the biology better and develop effective, personalized treatment options. Research Sponsor: None.

RASalt group had less favorable outcomes while APCalt group had more favorable outcomes, regardless of treatment received and sidedness. LRT indicated that when genomics was added to the sidedness evaluation, there was an improvement in outcome prediction (p,0.001), but not when sidedness was added to genomics. Conclusions: Tumor genomics better explains differences in outcomes than sidedness in 1 st line treatment in mCRC. Research Sponsor: Foundation Medicine, Inc.

). Patients whose baseline serum AGLP-2 levels with 40,000 pg/ml or above showed relatively shorter overall survival (median 31.4 months with 95% CI, 14.4-38.6) compared with patients with serum AGLP-2 level below 40,000 pg/ml at baseline (median 38.6 months with 95% CI, 23.6-127.3), but not statistically significant (p=0.0946). There was no survival difference observed according to serum AGLP-2 levels at disease progression on the first line bevacizumab-containing chemotherapy.

Our primary outcome was to evaluate the rate of recurrence in patients with metastatic CRC who had curative resection in two different population, ctDNA positive or ctDNA negative, postsurgery. Results: We identified 35 patients with a median age of 55 years (range 31 -82) at the time of metastatic diagnosis. In this study cohort, 20 (57%) were female; 23 (66%) were white, and 10 (29%) were African American. 22 (63%) patients had left-sided primary tumors and the remaining (47%) had right-sided primary tumors. At the time of presentation, 23 (66%) patients had synchronous metastases and 12 (34%) developed metachronous metastases. ctDNA positivity was reported in 21 (60%) pts post-curative therapy. Median time from curative therapy to ctDNA positivity was 62 days. 22 (63%) pts experienced recurrence of disease post-curative resection. Median time to recur-

Investigating the association of WNT pathway dysregulation and youngonset colorectal cancer. First Author: Morgan Ferrell, University of Pittsburgh Medical Center, Pittsburgh, PA Background: Colorectal cancer (CRC) is the third most common cancer in the United States with studies showing increasing incidence of Young-Onset CRC, defined as cases occurring in individuals 50 years old or younger. Separately, the WNT Signaling Pathway and its subsequent mutation can result in sustained activation and, therefore, unregulated cell proliferation which has been well described in colorectal cancers. Loss of function in APC, AXIN1, AXIN2, GKS3B, and RNF43 can each act to dysregulate WNT signaling, contributing to cancer development. In this study, we aimed to conduct a comprehensive, molecular evaluation of the WNT signaling pathway in colorectal cancer within age-specific cohorts with onset of CRC at 50 years old or less versus greater than 50 years old. Methods: We used published individual patient-level data of 6286 patients with colorectal cancer (CRC) from the 16 CRC datasets included in the cbioportal database. The WNT pathway alterations, including APC, AXIN1, AXIN2, GKS3B and RNF43 mutations were considered to define the WNT mutant CRC cohort. The presence of WNT alterations according to the age (50 years old or younger vs. over 50 years) were evaluated using Chi-square tests. The association between primary tumor distribution (colon vs. rectal) and age were evaluated across patients with and without WNT pathway alterations. The effect of WNT pathway alterations on the overall survival and survival after the metastatic stage was evaluated with Kaplan-Meier survival curves. A type-I error level of 5% (p,0.05) was considered the threshold limit for statistical significance. Results: A total of 2,630 individuals were identified with relevant clinical and molecular information. When comparing WNT alteration patterns between young-onset CRC (, 50 years old) and CRC in cohort .50 years old, there was no statistically significant

Patient characteristics and data input to the GPT-4 model.

Overall 111,694 (92.8%)were MSS/MSI-low and 8,655 were MSI-H (7.2%). Among patients with reported MSI status, 52.1% were males and 47.9% were females. The mean age was 64.4 years. Most patients were whites (87.6%) and had insurance (96.8%), no existing comorbidities (70.4%), and grade 2 (70.8%) and AJCC Clinical Stage 4 (26.1%) GI cancer. A higher proportion of GI cancer patients with MSS/MSI-low utilized chemotherapy as first course compared to those with MSI high (48.2% vs 34.0%) whereas a lower proportion of GI cancer patients with MSS/MSI-low underwent a surgical procedure compared to those with MSI high (94.7% vs 97.1%). MSI status was reported most frequently in comprehensive community cancer program (40.3%) and academic center (34.8%), followed by integrated network phase 1b study of the OxPhos inhibitor ME-344 in combination with bevacizumab in refractory metastatic colorectal cancer. First Author: Patrick M Boland, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ Background: ME-344 is a synthetic small molecule that inhibits oxidative phosphorylation, resulting in energy starvation and cell death via caspase-dependent and -independent mechanisms. The activity of mitochondrial inhibitors is enhanced when mitochondrial respiration is upregulated, a situation achieved in solid tumors by inducing vascular normalization and hypoxia correction with antiangiogenics. In a CT26 colon carcinoma syngeneic murine model, ME-344 in combination with regorafenib showed significantly reduced tumor growth compared to regorafenib alone (Navarro et al. Cell Reports. 2016;15:2705). A randomized phase 0/1 window of opportunity study in HER2negative breast cancer showed significant decrease in the proliferation marker Ki67 in patients administered ME-344 plus bevacizumab vs. bevacizumab alone (Quintela-Fandino et al, Clin Cancer Res. 2020;26:35). The current study evaluates the safety and efficacy of ME-344 in combination with bevacizumab in refractory metastatic colorectal cancer, a clinical setting where continued antiangiogenic inhibition has established benefit. Prior phase 1-1b studies of ME-344 as a single agent and in combination have established the RP2D at 10 mg/kg when administered intravenously weekly. Methods: This is an open-label phase 1b study in patients $18 years old with metastatic colorectal cancer after failure of standard therapies, including fluoropyrimidine-, irinotecan-, and oxaliplatin-based regimens, anti-EGFR if RAS wild-type, PD/L-1-blocking antibody if MSI-H/dMMR, and BRAF-targeted therapy if BRAF V600E mutated. Other key eligibility criteria include measurable disease, ECOG performance status 0-1, adequate bone marrow, liver and renal function, no uncontrolled brain metastatic disease, no peripheral neuropathy grade $2, no uncontrolled hypertension or diabetes, and no increased hemorrhagic risk. Enrollment will proceed in 2 cohorts of 20 patients each.

randomized controlled trial of CAPEOX vs observation in patients with early-stage colorectal cancer with positive MRD after curative surgery (CAREME).First Author: Ke-Feng Ding, Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China Background: Most patients (pts) with early-stage colorectal cancer (CRC) have a good prognosis, but some still relapse shortly after surgery.Effective methods to assess the risk of recurrence in these pts and guide adjuvant chemotherapy (ACT) decision-making are lacking.Increasing studies have shown that circulating tumor DNA (ctDNA) can detect minimal residual disease (MRD) and identify pts with a high risk of recurrence.ACT could improve survival of MRD-positive pts with stage Ⅱ CRC suggested by recent studies, whether it is appropriate for those with stage Ⅰ or clinically low-risk stage Ⅱ CRC remains unknown.Methods: CAREME is a multicenter randomized controlled clinical trial aimed at investigating the benefit of chemotherapy for MRD-positive pts with earlystage CRC.Pts with resected stage Ⅰ or Ⅱ CRC will be evaluated by oncologists.Those who did not receive neoadjuvant therapy and are deemed suitable for active surveillance (i.e., ACT is not needed) will undergo a postoperative ctDNA test using MinerVa MRD assay (a tumor-informed assay covering 769 cancer-related genes).Pts with mismatch repair-deficient tumors will be excluded and stage Ⅱ pts should have no traditional highrisk features according to clinical practice guidelines.Pts with positive ctDNA (N = 38) will be equally randomized into two groups: treatment group (Arm A) or surveillance group (Arm B).Arm A will receive 8 cycles of CAPEOX therapy while pts in Arm B will not receive any ACT; both groups will undergo ctDNA tests at 6 months after randomization and be followed up every 3 months.The primary endpoint is 18-month recurrence-free survival, and a key secondary endpoint is ctDNA clearance at 6 months after randomization.Tumor samples from the pts will be collected forMRDassay and exploratory research. Accrual started in February 2023. Support: Genecast Biotechnology Company. Clinical trial information: NCT05699746. Research Sponsor: None. First Author: Hideaki Bando, Division of Drug and Diagnostic Development Promotion, Department for the Promotion of Drug and Diagnostic Development, National Cancer Center Hospital East, Kashiwa, Japan Background: Neoadjuvant radiotherapy and chemotherapy followed by surgical resection is a standard treatment for LARC. As anti-PD-1 therapy for patients with dMMR colorectal cancer is responsive in the context of metastatic disease, several clinical trials which evaluate the efficacies of anti-PD-1 therapy in patients with dMMR LARC are ongoing and suggested the outstanding responses (Cercek A. et al., N Engl J Med 2022). Methods: We initiated the EPOC 2201 VOLTAGE-2 study, which is an ongoing, nonrandomized, single-arm phase II trial. The major eligibility criteria were as follows: treatment-naïve with rectal cancer located 12 cm from the anal verge; confirmed dMMR; clinical stage II/III in primary cohort (N=35) and stage I in exploratory cohort (N=20); age $ 18; Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; and presence of sufficient organ function. The study treatments include 12 cycles of nivolumab (NIVO) monotherapy (240 mg every 2 weeks) followed by assessment using Memorial Sloan Kettering (MSKCC) Regression Schema (Smith J.J. et al., BMC Cancer 2015). If clinical complete response (cCR) or near complete response (nCR) are observed, non-operative management with additional 12 cycles of NIVO will be performed. If incomplete response (IR) is observed, standard chemoradiotherapy with 50.4Gy of radiation plus capecitabine followed by surgery will be performed. The primary endpoint is the 2-year cCR rate in primary cohort. Various survival endpoints including progression-free survival (PFS) and overall survival (OS) are assessed as secondary endpoints. Safety analyses are performed using the Common Terminology Criteria for

Zanzalintinib (XL092) plus atezolizumab versus regorafenib in previously treated MSS/MSI-low metastatic colorectal cancer (mCRC): The randomized phase 3 STELLAR-303 study.First Author: Anwaar Saeed, University of Pittsburgh Medical Center, Pittsburgh, PA Background: Patients with microsatellite stable/microsatellite instability-low (MSS/ MSI-low) mCRC account for ~95% of mCRC cases, and there is a significant unmet need in patients with treatment-refractory MSS/MSI-low mCRC.Although immune checkpoint inhibitors (ICIs) have shown limited activity in this patient population, the addition of tyrosine kinase inhibitors (TKIs) may increase sensitivity to ICIs by promoting an immune-permissive tumor microenvironment.Furthermore, TKI-ICI combinations have demonstrated encouraging clinical activity in patients with mCRC, particularly in subgroups of patients without liver metastases (LM).Most recently, in the phase 3 LEAP-017 study of patients with non-MSI-high/mismatch repair deficient (dMMR) mCRC, although pembrolizumab + lenvatinib did not improve overall survival (OS) vs standard of care, subgroup analysis suggested the potential for clinical benefit in patients without LM (Kawazoe et al,ESMO-WCGI 2023).Zanzalintinib is a novel multi-kinase inhibitor targeting VEGFR, MET, and the TAM kinases (TYRO3, AXL, MER).In a phase 1 study, zanzalintinib alone and in combination with atezolizumab (an anti-PD-L1 ICI) showed preliminary anti-tumor activity and a manageable safety profile across multiple tumor types(Sharma et al, ESMO 2022). Methods: STELLAR-303 (NCT05425940) is a global, randomized, open-label phase 3 study to assess the efficacy and safety of zanzalintinib + atezolizumab versus regorafenib in adult patients with MSS/MSI-low mCRC. Patients must have documented MSI/MMR status (non-MSI-high/dMMR) and RAS status by tissue-based analysis, measurable disease per RECIST v1.1, ECOG PS 0 or 1, and radiographic progression during/after or intolerance to standard of care treatments for versus mFOLFOX 6 as adjuvant treatment for high-risk stage III colon cancer (FROST trial): Study protocol for an open label, multicenter, randomized, phase II study. First Author: Kyung-ha Lee, Department of Surgery, Chungnam National University Hospital, Chungnam National University College of Medicine, Dajeon, South Korea Background: Patients with high-risk stage III colon cancer have a significantly poorer prognosis than those with stage II or low-risk stage III colon cancer. Despite this distinction, most guidelines recommend similar adjuvant treatment approaches for all stages, and there is a dearth of research focusing on high-risk stage III colon cancer and the potential for improved prognosis through more intensive adjuvant treatment.

Node-sparing modified short-course radiotherapy combined with CAPOX and tislelizumab for locally advanced MSS of middle and low rectal cancer (mRCAT): An open-label, single-arm, prospective, multicentre clinical trial. First Author: Zhangfa Song, Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China Background: Neoadjuvant chemoradiotherapy followed by total mesorectal excision is a standard treatment for locally advanced rectal cancer. Mismatch repair-deficient locally advanced rectal cancer was highly sensitive to PD-1 blockade. However, most rectal cancers are mismatch repair-proficient or microsatellite stable subtypes for which PD-1 blockade is ineffective. Radiation can trigger the activation of CD8+ T cells, further enhancing the responses of microsatellite stable rectal cancer to PD-1 blockade.

Randomized phase II trial of encorafenib and cetuximab with or without nivolumab for patients with previously treated, microsatellite stable, BRAF V600E metastatic and/or unresectable colorectal cancer. First Author: Van K. Morris, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX Background: Patients with microsatellite stable (MSS), BRAF V600E metastatic colorectal cancer (mCRC) experience poor survival outcomes. Treatment with the BRAF inhibitor encorafenib (E) and anti-EGFR antibody cetuximab (C) is an approved treatment combination, with a reported overall response rate (ORR) of 20% and median progression-free survival (PFS) of 4.1 months. Anti-PD-1 antibodies like nivolumab (N) are ineffective as monotherapy for patients with MSS, BRAF V600E mCRC. In preclinical models of MSS, BRAF V600E CRC, inhibition of BRAF and EGFR induces a loss of expression of mismatch repairs genes and promotes a microsatellite instability-high phenotype, which may prime these tumors for response to immunotherapy. In support of these findings, a single-institution clinical trial of E + C + N for 26 participants with MSS, BRAF V600E mCRC reported an ORR of 50% and median PFS of 7.2 months. We hypothesize that the addition of N to E + C will improve PFS for participants with MSS, BRAF V600E mCRC. Methods: In this prospective phase II clinical trial (N=75), participants with previously treated MSS, BRAF V600E mCRC will be randomized 2:1 into 2 arms, respectively: experimental treatment (E + C + N) or standard treatment (E + C). No prior BRAF, EGFR, or immunotherapy agents are allowed. All participants will receive E (300 mg PO daily) and C (500 mg/m 2 IV every 14 days), and participants in the experimental arm will receive N (480 mg IV every 28 days). The primary endpoint is PFS. Secondary endpoints include overall survival, best overall response, duration of response, and safety/tolerability. Using a one-sided a= .10 and power 80%, we target an improvement in median PFS from 4.2 to 7.3 months and a hazard ratio of 0.57. Additional participants specimens will be collected for exploratory correlative research. As of 9/2023, 37 of 75 planned participants have been enrolled. Clinical trial information: NCT05308446. Research Sponsor: NCI; The Hope Foundation for Cancer Research STrS award.

Second colorectal cancer clinical validation study to predict recurrence using a circulating tumor DNA assay to detect minimal residual disease. First Author: Mohamed E. Salem, Levine Cancer Institute, Charlotte, NC Background: Detectable circulating tumor DNA (ctDNA) after resection of early-stage solid tumors has been associated with very high risk of recurrence, suggesting ctDNA is evidence of minimal residual disease (MRD). Several studies are ongoing to investigate the role of ctDNA in the optimal management of patients (pts) with colorectal cancer using different assay technologies. Methods: This is a prospective, observational, multicenter study in the United States and Canada of 750 pts who have undergone complete surgical resection for stage II or III colorectal cancer, who have FFPE tissue available from the primary resection sufficient for a novel bespoke MRD assay and are willing to provide serial whole blood specimens for ctDNA analysis. Participants are asked to provide study specimens after definitive surgical resection, pre-recurrence follow-up, and clinical recurrence (if applicable).

Results:A total of 618 patients with LGD (median age of 64 years old) were followed up for a median of 30 months and local recurrence has happened in 21 patients (3.4%).Multivariate analysis showed lesion size (hazard ratio 1.06, 95% confidential interval 1.01-1.12)wasassociatedwiththelocalrecurrence.Among 557 lesions smaller than 10 mm, local recurrence was found in 14 cases (2.6%) and local recurrence was in 7 cases (9.5%) of 109 tumors larger than 10 mm (p ,0.004).Conclusions: In gastric LGD smaller than 10 mm without scars, APC is a good treatment modality in place of ER.However, when a lesion is larger, APC should be selected carefully with close monitoring.Research Sponsor: None.recurrencerate after APC according to lesion size and submucosal saline injection.Infusional fluorouracil and weekly docetaxel as first-line therapy for gastric cancer with bone marrow metastasis and disseminated intravascular coagulation: A multi-center, phase II trial (Zhen Long).First Author: Jian Xiao, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaBackground: Gastric cancer (GC) with bone marrow metastasis (BMM) and disseminated intravascular coagulation (DIC) constitute a highly aggressive GC (HAGC) sub-type with distinctive features.The prognosis is poor and most HAGC patients die in weeks without effective treatment.Undue concerns about the myelosuppression mitigate against the application of cytotoxics in HAGC which is characterized by thrombocytopenia.Retrospective analysis showed low dose chemotherapy might relieve the DIC and bring with survival benefit but the standard of care(SOC)has not yet been established without a prospective study available.We completed a multi-center phase II trial evaluating the safety and efficacy of infusional fluorouracil and weekly docetaxel as first-line (1L) treatment for HAGC.Methods: This was a single-arm trial.A Simon's two-stage optimal design was applied.Eligible cases were: 18-75 years old, histologically confirmed GC, established BMM, overt DIC, platelet # 50*10 9 /L and Eastern Cooperative Oncology Group (ECOG) performance status (PS) # 3. Fluorouracil 200mg/m 2 /d continuous infusion on days 1-21 and docetaxel 25mg/m 2 /d on days 1, 8, 15 were given every four weeks.Hematological response (HeR) was defined as the platelet restored to normal range.The primary end point was HeR rate.Secondary end points were time to HeR (TTHeR), one month mortality (OMM), overall survival (OS), adverse events (AEs) and quality of life (QoL).Results: From Jan 2021 to Sep 2022, 24 HAGC cases from three Chinese centers were enrolled (details shown in table below).20 HeRs were achieved and the HeR rate was 83.3%.Median TTHeR was 13 days and OMM was 12.5%.Till the data cut-off date (Jul 31, 2023), 3 patients were still alive with a median follow-up of 403 days.The median OS was 242 days.Totally, twelve Grade 3 AEs were recorded in 7 (29.2%)patients, among which stomatitis (4, 16.7%) and aminotransferase elevation (3, 12.5%) were the most frequent.No drug-related grade 4 or 5 AEs were observed.QoL outcomes were significantly improved both during and after the treatment.Conclusions: Anti-cancer treatment is the key point to control DIC of HAGC.The Zhen Long regimen was well tolerated and showed promising efficacy in the 1L setting.It should be considered as the SOC in current practice, but further randomized trials are still needed.Clinical trial information: NCT04547153.Research Sponsor: Wu Jieping Medical Foundation.Survival outcomes in patients with resectable gastric cancer treated with total neoadjuvant therapy. First Author: Yun Song, The University of Texas MD Anderson Cancer Center, Houston, TX Background: Perioperative chemotherapy is the standard of care for patients diagnosed with advanced gastric cancer. However, the use of total neoadjuvant therapy (TNT), which includes both chemotherapy and chemoradiation, is increasing in other malignancies. The purpose of this study is to determine overall survival (OS) in a contemporary cohort of gastric cancer patients treated with TNT and surgical resection. Methods: Patients diagnosed with microsatellite-stable clinical T2+ or N+ gastric adenocarcinoma (January 2012 to June 2022) were identified from a prospectively maintained institutional database. Those who underwent staging laparoscopy and received neoadjuvant chemotherapy and chemoradiation therapy, followed by gastrectomy, were included in the study. OS and variables associated with OS were determined using standard statistical methods. Results: Of 203 study patients, the median (interquartile range) age was 61 (50-69.5) years and 50 (24.6%) had tumor involving the gastroesophageal junction. The most common TNT sequence was chemotherapy followed by chemoradiation, which was utilized in 173 (85.2%) patients. The chemotherapy regimen typically given was fluorouracil and oxaliplatin in 149 (73.4%) patients. The most common radiation dose was 45 Gy in 25 fractions (169 [83.3%] patients), with 18 (8.9%) patients receiving 30 Gy in 10 fractions. One hundred ninetyseven (97.0%) patients completed all their planned neoadjuvant therapy.

Recently, PD-1 blockades combined with dual chemotherapy in first-line setting exhibited encouraging efficacy for patients with ESCC.However, the safety profile of conventional dual chemotherapy remained unsatisfactory.Therefore, PD-1 blockades combined with anti-angiogenic tyrosine kinase inhibitors (TKIs) and single chemotherapy regimen might be a promising strategy.Anlotinib, a novel multitarget TKI primarily targeting VEGFR1-3, demonstrated promising therapeutic activity as first-line combination therapy or second-line monotherapy for patients with ESCC in China clinically.Therefore, this study was designed to explore the efficacy and safety of anlotinib combined with penpulimab (PD-1 blockade) and nab-paclitaxel as first-line therapy in advanced ESCC.Methods: Patients with previously untreated metastatic or locally advanced ESCC were recruited and treated with anlotinib (12mg, po, d1~14, q3w) and penpulimab (200mg, iv, d1, q3w) plus nab-paclitaxel (220mg/m 2 , iv, d1, q3w) until disease progression or unacceptable toxicity.The tumor response was assessed according to RECIST 1.1 using CT scans every two cycles.Adverse events were recorded by severity in accordance with the NCI CTC AE Version 5.0.The predefined sample size was 30.Primary endpoint was PFS and secondary endpoints included safety, ORR, DCR and OS.Results: From Jul 2022 to Aug 2023, a total of 23 patients were enrolled, 19 patients who had received first tumor response were included in this analysis.Initial safety assessment of the endoscopically injected oncolytic virus OBP-301 in medically inoperable esophageal cancer: NRG-GI007. First Author: Geoffrey Yuyat Ku, Memorial Sloan Kettering Cancer Center, New York, NY Background: Definitive chemoradiation (CRT) is a standard-of-care for patients (Pts) with medically inoperable esophageal cancer (EC). The NRG/RTOG 0436 study of cisplatin/ paclitaxel and RT (+/-cetuximab) as definitive therapy showed that about half of Pts have locally persistent disease. OBP-301 is a conditionally restricted, replication-competent adenovirus derived from human adenovirus type 5 that adds a human Telomerase Reverse Transcriptase (hTERT) gene promoter, replicating only in tumor cells to cause lysis. It may cause immunogenic cell death, enhance RT, and improve local control. OBP-301 was previously studied with RT in Japanese esophageal cancer Pts and shown to be safe and has promising activity. 1 Methods: In NRG-GI007, a phase 1 study (NCT04391049), OBP-301 is added to weekly carboplatin/paclitaxel and RT (50.4 Gy/28 fractions) for Pts with medically inoperable EC. Pts receive 1-2mL of intratumoral OBP-301 1310 12 virus particles/ml via endoscopy 3 days prior to and then at days 12 and 26 of CRT. The primary endpoint is doselimiting toxicity (DLT), defined as adverse events (AEs, by CTCAE v5) definitely or probably attributed to OBP-301 that meet either of the following: (1) leading to a .14-day cumulative delay in CRT or (2) any grade $ 3 AE EXCEPT: grade 3 nausea/vomiting, grade 3 esophagitis or dehydration, first occurrence of grade 3/4 neutropenia, or grade 3/4 lymphopenia. Initially, 6 evaluable Pts (eligible and started protocol treatment) are enrolled. If protocol defined DLT occurs in #1 of 6 Pts, the dose will be deemed safe and an expansion cohort of 9 more will be enrolled to further assess safety and obtain a preliminary assessment of clinical complete response. If $2 Pts have a DLT then one de-escalated OBP-301 dose will be assessed. Results: From June 2020 to April 2023, 6 evaluable Pts were enrolled. Median age was 73.5 years, all male. Five Pts had adenocarcinoma and 1 had squamous cell carcinoma; 3 Pts had node-positive disease. All Pts received all planned OBP-301 injections, along with 50.4 Gy RT. Four out of 6 Pts received all 5 weekly doses of chemo for . 85% of planned total dose, and 2 got 4 weekly doses for . 70% of planned total dose. No Pt experienced ³7 day treatment delay. The following treatment-related (attributed as definitely, probably, or possibly related to CRT and/or OBP-301) grade 3 AEs were reported across 5 Pts: decreased neutrophil count (3 Pts), decreased lymphocyte count (2 Pts), decreased WBC (2 Pts), and fever and fatigue (1 Pt each). There were 4 Pts with AEs reported as definitely or probably related to OBP-301, all grade #2. No DLT occurred.

: A total of 74 patients were included in this study(CapeOX 31/ DS 43).Patient characteristics (CapeOX/DS) were as follows: median age, 60/64 years; male, 77/65 %; ECOG-PS 0/1, 45%/44%, 55%/56 %; p stage IIIA/IIIB/IIIC, 10%/30%, 48%/51 %, 42%/19 %.The 3-year RFS was 37% in the (hazard ratio [HR] = 0.81, P=0.48).For p stage IIIA, IIIB, and IIIC, the 3-year RFS in the CapeOX group and the DS group was 67% vs. 75% (HR = 0.56, P =0.52), 43% vs. 42% (HR = 1.11,P =0.81), and 23% vs. 0% (HR = 1.59,P =0.39), respectively.Multivariable analysis adjusted for p stage showed no significant differences in RFS between the CapeOX group and the DS group (HR=1.06,P=0.85).Compared to DS, CapeOX was associated with lower incidences of febrile neutropenia (0% vs 7%) and alopecia (6% vs 74%), and a higher incidence of peripheral neuropathy (80% vs 23%).Conclusions: This analysis indicates that CapeOX and DS have comparable efficacy as adjuvant chemotherapy for p stage III GC in terms of RFS, albeit with different profiles of AEs.Research Sponsor: None.The advantages of robotic gastrectomy (RG) for gastric cancer are being demonstrated.However, there are few reports that have focused on advanced gastric cancer and examined the advantages of RG for laparoscopic gastrectomy (LG).We conducted the following study to clarify the advantages of RG for advanced gastric cancer.Methods:This single-center retrospective study reviewed the clinical data of 1531 patients who underwent either RG or LG from 2014 to 2023.473 patients were with clinically diagnoses as having advanced gastric cancer.They were divided into the RG group (n = 143) and the LG group (n = 330).Propensity score matching was employed to adjust the background of the two groups, as covariates of age, gender, BMI, surgical method (distal gastrectomy/total gastrectomy), stage (early cancer/advanced cancer), and presence or absence of preoperative chemotherapy.Then, the treatment results were compared and examined.Results: 130 patients in each group were extracted by propensity score matching.There were no significant differences in age, gender, and ECOG-PS between the two groups.Compared to the LG group, the RG group had more cases with deeper invasion depth $T3 (93.1 vs 84.6%, P = 0.04), more D2 dissection (96.9 vs 88.5%, P = 0.01), and longer operative time (339.5 vs 294.5min,P ,0.01).The number of retrieved lymph nodes was larger (49.5 vs. 44, P ,0.01) in the RG group.Neoadjuvant chemotherapy (NAC) followed by D2 gastrectomy with paraaortic lymph node dissection (PAND) is the standard treatment for gastric cancer with extensive lymph node metastasis (ELM) in Japan.ELM includes bulky lymph node metastasis along the celiac artery and its branches (Bulky N2) and metastasis of paraaortic lymph nodes (PAN).However, the benefit of PAND for gastric cancer with Bulky N2 but without PAN involvement is unclear.The aim of this study was to evaluate the efficacy of prophylactic PAND after NAC for this subgroup of patients.Methods: We retrospectively reviewed 21 patients who underwent NAC followed by curative (R0) gastrectomy for Bulky N2 (+) but PAN (-) gastric cancer from 2008 to 2019.Bulky lymph node was defined as one lymph nod es $ 3cm or two adjacent lymph nodes $ 1.5cm each.PAN metastasis included no.16a2/16b1 lymph node metastasis.PAND was defined as systematic lymph node dissection of PAN.Patients were divided into two groups: a D2+PAND group (11 patients) and a D2 group (10 patients).We compared the clinicopathological features, recurrence patterns, and survival outcomes between the two groups.Results: The most common NAC regimen was S-1+cisplatin (12 patients:First-line pembrolizumab (pembro) plus chemotherapy (chemo) for advanced gastroesophageal junction cancer (GEJC) and esophageal adenocarcinoma (EAC): Analysis of KEYNOTE-590 and KEYNOTE-859 by tumor type.First Author: Zev A. Wainberg, David Geffen School of Medicine at UCLA, Los Angeles, CA Background: First-line (1L) treatment of GEJC and EAC is similar to that for gastric adenocarcinomas, based on evidence from 2 large phase 3 gastric and esophageal cancer trials.The phase 3 KEYNOTE-590 trial (NCT03189719) showed 1L pembro + chemo significantly improved OS and PFS in pts with esophageal cancer.The phase 3 KEYNOTE-859 trial (NCT03675737) showed 1L pembro + chemo significantly improved OS, PFS, and ORR in pts with HER2-negative gastric cancer or GEJC.This post hoc, exploratory analysis was conducted to examine the efficacy of 1L pembro + chemo in the GEJC and EAC subgroups of KEYNOTE-590 and the GEJ subgroup of KEYNOTE-859.Methods: Pts with untreated advanced EAC or Siewert type 1 adenocarcinoma of the GEJ (KEYNOTE-590) or HER2-negative GEJ adenocarcinoma (KEYNOTE-859), measurable disease per RECIST v1.1, and ECOG PS 0 or 1 were evaluated.In both studies, pts were randomly assigned 1:1 to receive pembro 200 mg IV or pbo every 3 wk (Q3W) for #35 cycles, each with chemo (5-fluorouracil + cisplatin[FP]in KEYNOTE-590; FP or capecitabine + oxaliplatin in KEYNOTE-859). Efficacy end points for this analysis were OS and PFS (per RECIST v1.1 by blinded independent central review) by tumor subtype. Database cutoff was July 2, 2020, for KEYNOTE-590 and July 1, 2022, for KEYNOTE-859. Results: Overall, 201 pts from KEYNOTE-590 (n=99 pembro + chemo; n=102 pbo + chemo) with GEJC or EAC and 334 pts from KEYNOTE-859 (n=149 pembro + chemo; n=185 pbo + chemo) with GEJC were included. In KEYNOTE-590, 91 pts had GEJC only (n=41 pembro + chemo; n=50 pbo + chemo) and 169 (n=82 pembro + chemo; n=87 pbo + chemo) had GEJC + EAC + CPS $1. In KEYNOTE-859, 287 pts (n=123 pembro + chemo; n=164 pbo + chemo) had GEJC + CPS $1. Demographic and baseline characteristics were well balanced. Median time from randomization to database cutoff for pts with GEJC and EAC was 23.5 mo (range, 15.3-33.6) in KEYNOTE-590 and 25.8 mo (range, 12.4-43.0) in KEYNOTE-859. Efficacy outcomes by tumor type are shown in the Table. Conclusions: Consistent with results from the ITT populations of KEYNOTE-590 and KEYNOTE-859, 1L pembro + chemo provided clinically meaningful improvement in OS and PFS vs chemo in pts with untreated advanced GEJC and EAC. These data support the use of 1L pembro + chemo for pts with advanced GEJC and EAC. Clinical trial information: NCT03189719 and NCT03675737. Research Sponsor: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Benefit of immune checkpoint inhibitors (ICI) for patients with advanced esophageal squamous cell carcinoma and low PD-L1 expression: A systematic review and meta-analysis. First Author: Mario Machado Lopes, A.C. Camargo Cancer Center, S ão Paulo, Brazil

The secondary endpoints included safety, 1-year DFS rate, 3-year DFS rate, 1-year overall survival (OS) rate, and 3-year OS rate. Results: Between August 18, 2022, and August 25, 2023, a total of 12 patients were enrolled. Out of the 12 surgically resected cases of ESCC, 11 (91.7%) had an ECOG score of 1, 10 (83.3%) were male, and 6 (50%) were under the age of 65. According to the eighth edition of the AJCC

Surgery is the cornerstone of curative therapy for localized GC or EGJC and perioperative chemotherapy seems ineffective for those with dMMR/MSI-H tumors. Chemotherapy may booster antitumor immunity. There is a compelling need to investigate the efficacy of perioperative immunochemotherapy for those with dMMR/MSI-H tumors. Methods: NICE trial is a multicenter, multi-cohort phase II trial (NCT04744649) investigating the safety and efficacy of toripalimab combined with CapeOX regimen as perioperative treatment for localized GC or EGJC of PD-L1 CPS$5 (IHC 22C3) (cohort A), EBV-positive (cohort B), and dMMR/MSI-H (cohort C). Among those cohorts, the cohort A was compared with the control group of perioperative CapeOX regimen in a randomized controlled trial manner, while the cohort B and C were single arm. In present study, we report the findings of Cohort C, and the patients (pts) received toripalimab 240 mg combined with standard dose CapeOX regimen q3 weeks for 4 cycles before and after surgery. The eligible tumor stages were cT3-4aNxM0 or cT2N+M0 diagnosed by chest and abdominal CT combined with staging laparoscopy as well as negative peritoneal cytology. The primary endpoint was major pathologic response (MPR, ,10% viable cells) rate. Multiplex fluorescence immunohistochemistry (mIHC) was utilized to explore changes of immune microenvironment. Results: Between March 2021 and April 2023, 15 pts with dMMR/MSI-H localized GC/GEJC were recruited in Cohort C. Tumor stages were cT3N0(n=2), cT3N1-3 (n=2), cT4aN0 (n=1) and cT4aN1-3 (n=10). 14 pts completed all 4 cycles therapy preoperatively and one patient completed 2 cycles therapy because of AEs. None had disease progression, while one achieved a complete clinical response at radiology and endoscopy and refused surgery and the other 14 pts underwent resection. The R0 resection rate was 100% (14/14). The MPR rate was 92.9% (13/14) and the residual tumor percentage was 33.8% in the other one patient (cT4aN2). pCR rate was 78.6% (11/14). Therapy-related grade 3/4 AEs occurred in 5 pts of safety population (n=15). One patient occurred grade 3 immune-related liver toxicity after 2 cycles treatment and recovered after steroids therapy. No pts died during the perioperative treatment, and one patient died of COVID-19 238 days after surgery without relapse. No disease relapse was observed in all pts. The mIHC revealed a significant reduction in CD20+ B cells, CD3+ T cells, NK dim cells, and M1 macrophages within tumor area after treatment for patients who reached pCR. Conclusions: Neoadjuvant toripalimab and CapeOX regimen for the localized dMMR/MSI-H GC/GEJC is safety with high MPR rate. These data indicate that neoadjuvant immunochemotherapy may potentially become one of the treatment options for these patients. Clinical trial information: NCT04744649. Research Sponsor: None.

Conclusions: These results suggested promising anti-tumor activity and a manageable safety profile of Suru plus standard ChT in 2L treatment of aGC.The trial is still ongoing, and more data will be disclosed in the future.Clinical trial information: ChiCTR2200063336.Research Sponsor: HUTCHMED.HLX22 plus HLX02 and XELOX for first-line treatment of HER2-positive locally advanced or metastatic gastric/gastroesophageal junction cancer: A randomized, double-blind, multicenter phase 2 study.First Author: Jin Li, Department of Medical Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China Background: Gastric/gastroesophageal junction (G/GEJ) cancer represents a global healthcare challenge.With more than 1 million new cases estimated in 2020, it ranked fifth among all cancers.HER2 amplification or overexpression were reported in around 20% of advanced G/GEJ cancer cases.Despite the improved overall survival with trastuzumab plus chemotherapy, the prognosis remains unsatisfactory, and thus more effective treatments are needed.This study aimed to evaluate the combination of HLX22 (a novel anti-HER2 monoclonal antibody), HLX02 (a trastuzumab biosimilar), and chemotherapy for patients with G/GEJ cancer in the first-line setting.Methods: The study was unblinded 3 months after the last patient was enrolled. 23ULN or AFP positive by the IHC staining method were enrolled. Pts received 4 cycles of standard S-1 plus oxaliplatin (SOX) and camrelizumab (200mg, iv, d1, q3w) plus apatinib (250mg, po, qd). Pts without disease progression then continued to receive camrelizumab plus apatinib for up to 24 months, or until progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST v1.1; secondary endpoints included the duration of response (DoR), disease control rate (DCR), progression free survival (PFS), overall survival (OS) and safety. Results: A total of 36 pts were enrolled and received treatment between Dec 4, 2020 and Aug 4, 2023. 35 pts were evaluable for tumor response.

The primary endpoint was pathologic complete response (pCR) rate.Secondary endpoints included tumor regression grade (TRG), R0 resection rate, objective response rate (ORR) and safety profile.Results: From Jan 2023 to Sep 2023, 25 pts (19 males and 6 females) were enrolled with a median age of 67 years (range: 50-74).All pts were available for efficacy assessment and 16 were evaluable for the primary end point.The rest of the pts are waiting for surgery.As of 15 Sep 2023, 19 pts underwent esophagectomy and R0 resection rate was 87.5%.The pCR rate was 18.8% (3/16) and 31.3% of pts had a major pathologic Preliminary results of surufatinib (Suru) plus standard chemotherapy (ChT) as second line (2L) treatment of advanced gastric cancer (aGC): A singlearm, phase 2 clinical trial.First Author: Ting Han, Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Background: Limited options are available for aGC patients who have failed first line (1L) systemic treatment, and single-agent ChT with paclitaxel (Pac) or irinotecan (Iri) remains the mainstay.Recent studies have suggested improved efficacy with the combination of ChT and antiangiogenic agents in the 2L setting.Suru is a tyrosine kinase inhibitor targeting VEGFR1-3, FGFR1 and CSF-1R.This trial is aimed to evaluate the efficacy and safety of Suru plus Pac or Iri as 2L treatment for aGC.Methods: This single-arm, single center, phase 2 trial was designed to enroll up to 35 histologically confirmed HER2-negative aGC patients with evaluable disease who failed 1L ChT with or without immunotherapy (IO).Eligible patients were administered 21day cycles of Suru (250mg, po, qd) plus Pac (150mg/m 2 , iv, d1) or Iri (125mg/m 2 , iv, d1, d8) per investigator choice for 6 cycles, followed by Suru (250mg, po, qd) maintenance if no disease progression (PD), until intolerable toxicity, PD, or death.The primary endpoint was ORR (per RECIST v1.1), and secondary endpoints included DCR, PFS, OS, and safety.Results: As of Sep 11, 2023, 15 patients were enrolled, and 6 patients remained on treatment.The median followup time was 5.77 (95% CI: 3.37~10.13)months.Among all 15 patients, the median age was 66 (range: 33-76) years, 14 (93.3%) were male, and 14 (93.3%) had an ECOG PS of 1.Ten (66.7%) patients had received prior anti-PD-1 antibodies, and all 15 patients received Pac as the standard ChT.All 15 patients were evaluable for tumor response, with 5 PR, 9 SD, and 1 PD as their best overall response (BOR).The ORR and DCR were 33.3% and 93.3%, respectively.The median PFS was 5.23 months, while the OS data was immature yet.The ORR, DCR and PFS seemed comparable between patients with and without prior IO.In terms of safety, the combined treatment was generally well tolerated, treatment-related Grade 3/4 adverse events included neutropenia (6, 40%), leukopenia (1, 6.7%), lymphopenia (1, 6.7%), and proteinuria (1, 6.7%).There were no treatment-related serious adverse events or treatment-related deaths.Conclusions: These results suggested promising anti-tumor activity and a manageable safety profile of Suru plus standard ChT in 2L treatment of aGC. Methods: The study was unblinded 3 months after the last patient was enrolled.Patients with locally advanced or metastatic HER2-positive G/GEJ cancer and had not received prior systemic antitumor therapy were enrolled.The study consisted of 2 parts; current report will focus on part 1.In part 1, patients were randomized 1:1:1 to receive HLX22 25 mg/kg + HLX02 + XELOX (group A), HLX22 15 mg/kg + HLX02 + XELOX (group B), or placebo + HLX02 + XELOX (group C) in 3-week cycles.Primary endpoints were PFS and ORR assessed by IRRC per RECIST v1.1.Secondary endpoints included other efficacy measures and safety.Results: As of July 30, 2023 (data cutoff), 53 patients were randomized to group A (n=18), B (n=17), and C (n=18), and were followed up for a median of 14.3 months.44(83.0%)patientsweremale.Main efficacy results are presented in Table.Tumor assessments reported in Tablewereperformed by IRRC.Treatment-related adverse events (TRAEs) occurred in 18 (100.0%),16(94.1%),and 17 (94.4%)patients in the respective groups.Serious TRAEs were observed in 5 (27.8%) patients in group A, 1 (5.9%) in group B, and 1 (5.6%) in group C.Only 1 (5.6%) patient in group C had a grade 5 TRAE.Conclusions: Adding HLX22 to HLX02 + XELOX improved survival and antitumor response in patients with HER2-positive G/GEJ cancer in the first-line setting, with a manageable safety profile.Clinical trial information: NCT04908813.Research Sponsor: Shanghai Henlius Biotech, Inc.The primary endpoint was the pathologic complete response (pCR) rate.Initially, 6 Pts were enrolled to evaluate for toxicity; they received RT to 50.4 Gy.Subsequently, RT was lowered to 41.4 Gy to decrease the length of preop treatment (tx).Results: 16 pts have been enrolled.All Pts had clinical $T3 and/or N+ disease.PD-L1 CPS was $1 in 9 (60%) of 15 tested. 1 Pt (6%) had a microsatellite unstable (MSI) tumor.9(56%) Pts were PETr; 3 Pts (19%) were PETnr but had improved clinical symptoms and other PET parameters (MTV/TLG) and also continued with 5-FU/capecitabine and oxaliplatin during RT.Significant tx-related adverse events (AEs) are shown in the Table.Immune-related AEs (irAEs) were: gd 3 enterocolitis (1 Pt), gd 3/4 colitis (2 Pts, 12%), gd 1 diarrhea (1 Pt), gd 2 pruritis (1 Pt), gd 1 and gd 3 dermatitis (1 Pt each) and gd 2 arthralgias in 1 Pt. 1 Pt died of aspiration pneumonia while being treated for gd 4 colitis during CRT; 1 Pt developed gd 3 enterocolitis and cholecystitis during CRT, achieved a clinical CR and did not undergo surgery. He developed local recurrence and had surgery offstudy 16 months after start of tx; 1 Pt developed a bone metastasis after CRT. 4 Pts are awaiting restaging post-CRT. Of 9 Pts who had surgery, 4 achieved a pCR (44%, including the MSI Pt) and 3 (33%) had ypN0 tumors and ³90% tx response. All 9 Pts have initiated/completed adjuvant D+T. Conclusions: The addition of D+T to induction FOLFOX and PET-directed CRT prior to surgery is feasible, although irAEs seem numerically higher than in our prior study of D and CRT. Pathologic response data are promising. Accrual is ongoing and updated data will be presented. 1. Ann Surg 2023; 278:e511. Clinical trial information: NCT02962063. Research Sponsor: AstraZeneca. The primary objectives were safety and determination of the recommended Phase 2 dose (RP2D). Adverse Events (AEs) were graded per CTCAE 5.0, objective response rate (ORR), and clinical benefit rate (CBR) including CR, PR, and $6month SD were assessed by the investigator per RECIST 1.1. Results: As of May 14, 2023, twenty-four patients underwent leukapheresis in Cohort A. Nineteen patients (7 GC/GEJ and 12 PC) with a median of 3 (range: 1-8) prior therapeutic lines had satri-cel at three dose levels (DLs) between 250310 6 and 600310 6 cells. Seven patients received a 2nd dose and two patients received a 3rd dose of satri-cel at a median of 113 and 259 days, respectively, post-first infusion. All 19 patients experienced at least one AE. No DLTs occurred and 17 patients experienced cytokine release syndrome (CRS). Two cases of Grade 3 CRS were reported, and all other CRS were Grade 1 or 2. Two Grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS) occurred. All CRS and ICANS were resolved. No severe gastrointestinal-related AEs were found. No increased toxicities were reported after any reinfusion.

Surufatinib plus sintilimab in patients with advanced gastric/ gastroesophageal junction adenocarcinoma (GC/GEJC): A single-arm, open-label, single-center phase II trial.First Author: Dong-Sheng Zhang, Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China Background: Anti-PD-1 antibodies plus chemotherapy have become the standard first-line treatment for advanced GC/GEJC with CPS score $ 5.However, GC/GEJC still has dismal survival.Preclinical studies have demonstrated that surufatinib (a novel small-molecule kinase inhibitor targeting VEGFR1-3, FGFR and CSF-1R) combined with anti-PD-1 antibodies have synergistic antitumor effects by modulating tumor immune microenvironment.Therefore, a phase II trial to evaluate surufatinib plus sintilimab in patients (pts) with advanced GC/GEJC was conducted.Here we report the results of part A of this trial.Methods:This single arm, open-label, single center phase II trial consisted of two parts: part A (second-line therapy) and part B (first-line therapy).In part A, pts aged 18-75 years who were HER2-negative, failed firstline standard therapy, and immune checkpoint inhibitor therapy naive were enrolled.PartA included safety run-in and dose expansion stages.Six pts in the safety run-in received surufatinib at 250mg once daily as starting dose, in combination with a fixed dose of sintilimab (200 mg, d1, Q3W).If more than 1 DLT occurred in stage 1, the recommended dose of surufatinib for stage 2 (N=11) would de-escalate to 200 mg, otherwise would maintain as 250mg.The primary endpoint was ORR per RECIST v1.1.Secondary endpoints included DCR, PFS, OS and safety.If the ORR of part A was $ 30%, the trial would proceed to Part B (N=44), further evaluating this combination treatment in previously untreated advanced GC/GEJC.Results: At data cutoff on 8/10/2023, 16 pts (6 in safety run-in; 10 in dose expansion) were enrolled in part A. The median age was 56 years; 75% male; 69% with ECOG PS 1. Peritoneum (56%) was the most common metastatic site.No DLTs were observed in the safety run-in stage, so the recommended dose of surufatinib for dose expanding stage was 250 mg.Among the 16 pts evaluable for tumor response, 6 pts achieved PR, 4 pts achieved SD.The confirmed ORR and DCR per RECIST v1.1 was 40.0%(95%CI: 15.2-64.6%)and66.7%(95% CI: 38.4-88.2%),respectively.Median DOR was not reached and 50% of responders were estimated to have a response duration $ 7.8 months.Median PFS and OSwere not yet mature.Most TEAEs ($ 40%) were grade 1-2, including hypoproteinemia (62.5%), hypertension (50%), proteinuria (50%), lymphocyte count decreased (43.8%).The most common grade $ 3 TEAEs reported by 5 pts (31.3%) were blood bilirubin increased (18.8%), hypertension, lymphocyte count decreased, and alanine transaminase elevation (6.3%, respectively).No treatment-related death was reported.Conclusions: The results showed surufatinib plus sintilimab acquired preliminary efficacy and manageable safety profile as the second-line treatment for advanced GC/ GEJC.Part B is ongoing, and more data analysis will be reported further.Clinical trial information: NCT05235906.Research Sponsor: None.Safety of preventive HIPEC in combination with perioperative FLOT versus FLOT alone for resectable diffuse type gastric and gastroesophageal junction type II/III adenocarcinoma: An interim safety analysis from the phase III PREVENT trial of the AIO/CAOGI/ACO. First Author: Thorsten Goetze, Institute of Clinical Cancer Research (IKF) at Krankenhaus Nordwest, UCT-University Cancer Center and Frankfurter Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest, Frankfurt Am Main, Germany

Treatment arms were balanced regarding age, ECOG and tumor parameters like localization of the primary, of lymph nodes or cTN stage. Most pts in both arms received a subtotal or total gastrectomy. In 15 out of 20 arm B pts the HIPEC was 6 pts (30%) in Arm A and 7 pts (35%) in Arm B were seen with at least one SAE. Perioperative complications resulted in overall 7 SAEs in Arm A and in 4 SAEs in Arm B. One postoperative mortality (grade 5) was documented in Arm B due to septic complication. 11 pts showed no complications in both arms according to Clavien-Dindo-Classification. 6 pts in Arm A and 2 in Arm B showed grade 3. No patient was grade 4. Conclusions: The incidence of perioperative morbidity with surgical and/or medical complications were nearly equal in both treatment groups. The safety data showed no abnormalities or evidence increase in toxicity-rates including postoperative complications or increased severity of documented events within the experimental HIPEC arm. Clinical trial information: NCT04447352. Research Sponsor: Stiftung Deutsche Krebshilfe.

We queried the data for 334 patients with locally advanced GC (cT2-4 or cN+) diagnosed in 2016-2023 yy administered with multi-agent NCT: FLOT or XELOX/FOLFOX. The primary endpoints were the ratio of patients with disease progression on NCT, rates of ypN0, and rates of pathological complete response (pCR). Secondary endpoints included progression free survival (PFS) and overall survival (OS).

). Three patients had surgical complications (grade I in 1 patient [4%], grade IIIb in 1 [4%] , and grade IVa in 1 [4%]); there were no deaths within 90 days. The median follow-up time was 20 months, and median OS was not reached. One-and 3-year OS rates from the date of diagnosis were 96% and 80%, respectively. Conclusions: Short-course CXRT (30 Gy in 10 fractions) may be safely used as part of a planned TNT approach. Rates of treatment completion, pathologic response, and survival were promising, supporting further research into TNT for gastric cancer. Clinical trial information: NCT04523818. Research Sponsor: Holly Clegg Gastric Cancer Research Fund. phase 2, open-label study of amivantamab in patients with previously treated advanced or metastatic gastric or esophageal cancer. First Author: Daisuke Kotani, Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan Background: Amivantamab (Ami) is a bispecific antibody targeting epidermal growth factor receptor (EGFR) and mesenchymal epithelial transition receptor (Met) and has immune cell directing activity. Gastric cancer (GC), gastroesophageal junction (GEJ) cancer and esophageal cancer (EC) have been known to express EGFR and Met and these expressions have correlated with poor prognosis. Methods: This open-label, multicenter phase 2 study aims to evaluate the antitumor activity and safety of Ami monotherapy in patients (pts) with advanced or unresectable GC, GEJ cancer and EC who had received at least 2 prior lines (GC/GEJ) or 1 prior line (EC) of systemic therapy. Pts who express varying degrees of EGFR, Met, or both as determined by immunohistochemistry (IHC) were enrolled. Ami was administered intravenously at the recommended Phase 2 dose (RP2D) of 1,050 mg (or 1,400 mg if body weight $80 kg) in 28-day cycles. The primary endpoint was objective response rate (ORR) (RECIST 1.1). No hypothesis was planned but approximately 30 pts were to be enrolled in GC and EC cohorts, respectively. Secondary endpoints included disease control rate (DCR), pharmacokinetics (PK) and safety. Results: At the data cut-off of Jul-2023, a total of 59 pts received the RP2D. The 29 and 30 pts had GC/GEJ (all adenocarcinoma) and EC (29 squamous-cell and 1 adenocarcinoma), respectively. Median ages were 66 in GC/GEJ and 60 in EC, and 82.8% and 80.0% of pts were male, and median durations of study treatment were 0.99 and 2.64 months, respectively. The ORRs were 4.3% for GC/GEJ and 10.7% for EC and DCRs were 26.1% and 67.9%, respectively. The Met-high-expression (IHC score $2+) tended to be associated with better response of ORR 13.3% and DCR 80.0% compared to Met-low-expression (IHC score 1+/0) of ORR 7.7% and DCR 53.8% in EC. Transcriptomic analysis results from paired baseline/on-treatment EC biopsies will be presented. All 59 pts had adverse events (AEs) and 64.4% of them had AEs with the maximum grade of #2. Serious AEs occurred in 27.1% of pts. Conclusions: Ami showed clinical meaningful antitumor activity in EC, especially in Met-high-expression tumors. There was minimal monotherapy activity in GC. No new safety signals were identified in pts with GC and EC, which appeared to be acceptable. Clinical trial information: NCT04945733. Research Sponsor: Janssen Pharmaceutical K.K.

Methods: ESCC patients who were treated with Neo DCF between July 2016 and May 2023, were enrolled.Three courses of DCF (DTX [day 1]: 70 mg/m2, CDDP [day 1] : 70 mg/ m2, 5-FU [continuous infusion on days 1-5]: 750 mg/m2, every 3 weeks) were planned, and prophylactic antibiotics was administered on days 5-15.We retrospectively assessed disease free survival (DFS), pathological response, AEs.Pathological response was assessed according to the Becker's Criteria.Subgroup analyses of clinical factors related to the pathological response and AEs were also performed.Results: In total, 91 patients (median age, 62.3 years) were enrolled.Clinical stages of this cohort were 8.Updated pooled analyses of first-line anti-PD1/PD-L1 inhibitors plus chemotherapy in advanced esophageal squamous cell carcinoma. First Author: Maysa Vilbert, University of Pittsburgh Medical Center, Pittsburgh, PA Background: Advanced and metastatic esophageal squamous cell carcinoma (ESCC) patients have limited treatment options and poor prognosis. Recently, several studies demonstrated the clinical benefit of combining immune checkpoint inhibitors (ICI) and chemotherapy (CT), leading to its approval in the first-line setting. Since then, efforts have been made to identify the patients who may benefit the most or not from the combination of ICI plus CT. Methods: We searched PubMed, Scopus, and the Cochrane Library for randomized clinical trials investigating first-line ICI plus chemotherapy (CT) for advanced or metastatic ESCC patients. Outcomes of interest included: overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and OS according to gender, PD-L1 expression (,1% / $1%), and PD-L1 CPS (,10 / $10). We used I 2 statistics to assess heterogeneity, and the fixed-effect model was used to pool studies. Results: Eight studies were included with 4,702 patients. Of them, most had an ECOG 0 or 1, and were younger than 65 years (62%), male (77%), and Asian (78%). Metastatic disease was diagnosed in 75% of patients. ICI plus CT was administered to 58%, and 43% received CT +/-placebo. Median follow-up ranged from 7.1 to 22.6 months. ICI plus CT significantly improved all efficacy outcomes compared to CT alone: decreasing the risk of death by 32% (HR for OS: 0.68; 95%CI 0.63-0.74; p,0.00001); reducing the risk of progression or death by 38% (HR for PFS: 0.62; 95%CI 0.58-0.67; p,0.00001); and increasing the objective response rate (risk difference: 0.17; 95%CI 0.14-0.20; p,0.00001). A survival benefit was seen across all subgroup analyses, but it was significantly higher in patients with PD-L1 $1% compared to those with PD-L1 ,1% (reduction in the risk of death of 38% versus 23% respectively, p=0.03). OS was not significantly different between males versus females, or PD-L1 CPS$10 versus CPS,10. Conclusions: Our large systematic review and meta-analysis support the efficacy and survival benefit of ICI plus CT as first-line therapy for all ESCC patients, regardless of gender or PD-L1 expression. Research Sponsor: None.

Postoperative nutritional support is needed for patients especially those who underwent simultaneous gastrectomy.Research Sponsor: None.Safety and efficacy of zolbetuximab for CLDN18.2-positivegastric or gastroesophageal junction adenocarcinoma: A systematic review and metaanalysis of randomized controlled trials.First Author: Davi Said Gonçalves Celso, Federal University of Viçosa, Viçosa, Brazil Background: Monoclonal antibody (Nivolumab, Trastuzumab, Bemarituzumab) with chemotherapy has shown benefit for patients with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.Zolbetuximab, a new monoclonal antibody against Claudin (CDLN) 18.2 has demonstrated interesting results in clinical trials, however, there is still a need to find a safe and effective first-line treatment, especially for epidermal growth factor receptor (HER) 2-negative patients.Therefore, we aimed to perform a meta-analysis exploring the use of combined immunotherapy (Zolbetuximab) and standard chemotherapy versus chemotherapy alone.Methods: We searched PubMed, Embase and Cochrane Central for randomized controlled trials (RCTs) comparing Zolbetuximab to chemotherapy alone in patients with CLDN18.2-positivegastric or GEJ adenocarcinoma.The outcomes evaluated were Overall Survival (OS), Progression Free-Survival (PFS), Objective Response Rate (ORR) and Treatment-Emergent Adverse Events (TEAE).We pooled hazard ratio (HR) for PFS and OS endpoints and risk ratio (RR) for ORR and TEAE, with 95% confidence intervals (CI).Statistical analyses were performed using R software version 4.3.1 with a random-effects model.I² analysis was used to assess heterogeneity.Adverse Events (AE) were graded according to the National Cancer Institute Common Terminology Criteria for AE.Results: From sixty-six studies, three were included, with a total of 1349 patients.671 (49.7%) were part of the intervention group, 769 (57.0%) were male, 360 (26.7%) underwent prior gastrectomy and 1304 (96.7%) had a more than 70% CLDN18.2cellular staining rate.Age range was 21-83 years.Treatment with Zolbetuximab was associated with significantly higher PFS (HR 0.64; CI 0.49-0.84;p = 0.0011; I² = 59.6%) and OS (HR 0.70; CI 0.59-0.84;p,0.0001;I² = 40.0%).TEAEs grade $ 3 (RR 1.09; CI 1.03-1.16;p = 0.0051; I² =0.0%) were greater for the intervention group.ORR and serious TEAE had no difference when compared with the control group.Most frequent AEs were nausea (34.6%), vomiting (30.2%) and decreased appetite (18.6%).Conclusions: In summary, the use of Zolbetuximab alongside standard chemotherapy reduces mortality and disease progression, although it might increase the risk for grade $ 3 treatment-emergent AEs.Research Sponsor: None.Camrelizumab combined with concurrent chemoradiotherapy for locally recurrent esophageal cancer: A single-arm, open-label study. First Author: Ruinuo Jia, The 1st Affliated Hospital, Henan University of Science and Technology, Luoyang, China Background: Local recurrence is the main failure pattern after radical treatment of esophageal cancer. There is no uniform treatment specification for such patients(pts) so far. The combination of immune checkpoint inhibitors and concurrent chemoradiotherapy (CCRT) has emerged as a novel strategy to treat esophageal cancer. This research was to evaluate the efficacy and safety of camrelizumab (ICI targeting PD-1) combined with CCRT in the treatment of locally recurrent esophageal cancer.

The most common AEs included lymphocyte count decreased (11/14, 78.6%), neutrophil count decreased (5/14, 35.7%), white blood cell count decreased (5/14, 35.7%) and anemia (5/14, 35.7%). The most grade $3 AE was lymphocyte count decreased (6/14, 42.9%). No new safety signals or treatmentrelated deaths were observed. Conclusions: Current results suggested the promising efficacy and acceptable safety of camrelizumab combined with CCRT in pts with locally recurrent esophageal cancer. The study enrollment is ongoing, and further survival and safety data will be reported in the future. Clinical trial information: NCT04390945. Research Sponsor: None.

Patients (Pts) enrolled in the phase II G/ E adenocarcinoma cohort were administered cabo + durva at the RP2D of 40mg QD and 1500mg IV Q4W respectively.Enrolled pts must have progressed on .1 line(s) of systemic therapy.Prior exposure to PD-1/L1 inhibitors was allowed.Those with HER2 positive disease must have progressed on anti-HER2 therapies.The primary outcome was objective response rate (ORR).Secondary outcomes were treatment-related adverse events (TRAEs), disease control rate (DCR), progression free survival (PFS), and overall survival (OS).Exploratory subgroup analyses were conducted in PD-L1 CPS .5.Efficacy and safety of dendrimer-enhanced (DEP) cabazitaxel (CTX-SPL9111) in advanced esophagogastric cancers in a phase 1/2 trial.First Author: David James Pinato, Imperial College, London, United Kingdom Background: There is a significant unmet need in esophagogastric cancers (EGC) due to limited effective treatments (Tx) and poor prognosis.Dendrimers are highly branched nanoparticles that enable sustained delivery of cytotoxic drugs and achieve selective tumor targeting via an enhanced permeability and retention effect.DEP cabazitaxel is a highly optimised dendrimer formulation of cabazitaxel.Unlike standard cabazitaxel, DEP cabazitaxel is highly water soluble, does not contain toxic excipients such as polysorbate-80 associated with anaphylaxis, and avoids the need for steroid/antihistamine pre-medication.The objective of this Phase 1/2 trial was to assess preliminary efficacy and safety of DEP cabazitaxel in patients (pts) with advanced solid tumors including EGC, for which standard cabazitaxel is not approved.Methods:In the P2 part of the trial, advanced EGC pts with measurable disease were treated with DEP cabazitaxel 20 mg/m 2 cabazitaxel, the recommended Phase 2 dose, IV 3-weekly.Anti-tumour activity was assessed by RECIST v1.1, safety by CTCAE v4.03.(EudraCT 2017-003424-76). Results: Fifteen pts with advanced EGC were enrolled; 9 adenocarcinoma (ADENOCA) (3 gastric, 2 esophageal and 4 EG junction) and 6 esophageal squamous cell carcinoma (ESCC); median age 62 yrs (26-73 yrs), with all pts having #3 prior anticancer Tx, and the majority (9) having progressed on or immediately after 1 st line Tx (1L). All had $1 prior platinum-based regimen and 4 pts had received prior taxanes. Pts received a median of 4.5 DEP cabazitaxel cycles without the need for routine steroid/antihistamine or primary G-CSF prophylaxis. In all evaluable pts, disease control rate (DCR) was 80%. Disease control was observed in both histological subtypes and was durable, including stable disease (SD) for up to 27 weeks and partial responses (PR) for up to 17 weeks, with objective response rate (ORR) of 30%. In EG ADENOCA pts, DCR was 100%, ORR was 33%, and median progression free survival (mPFS) was 4.0 months. In ESCC pts, DCR was 50% and ORR was 25%, with mPFS of 1.9 months. Clinical trial information: NCT03281369.Research Sponsor: F. Hoffmann-La Roche Ltd/Genentech Inc.Network meta-analysis of global trials of 1L therapies in locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/ GEJ) adenocarcinoma.First Author: Manish A. Shah, Weill Cornell Medical College, New York, NY Background: The phase 3 SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) studies reported statistically significant improvement in PFS and OS with 1L zolbetuximab (anti-claudin-18 isoform 2 [CLDN18.2] )+mFOLFOX6 or CAPOX in pts with CLDN18.2+,HER22,LA unresectable or mG/GEJ adenocarcinoma.This network meta-analysis (NMA) indirectly compared the relative efficacy of 1L therapies.Methods: A systematic literature review of phase 2, 3, or unknown phase randomized, global trials of 1L therapies (capecitabine + cisplatin [CX]; capecitabine + oxaliplatin [CAPOX] ; fluorouracil + cisplatin [CF]; oxaliplatin + folinic acid + fluorouracil [FOLFOX] ; S-1 + cisplatin [SC]; nivolumab + CAPOX/FOLFOX; pembrolizumab + CF/CAPOX or CX; and zolbetuximab + CAPOX/FOLFOX) in adults with LA unresectable or mG/GEJ adenocarcinoma.To form a connected main network, FOLFOX and CAPOX were assumed equally efficacious and combined.In the latest publicly available data, hazard ratios (HRs) of PFS and OS for intent-to-treat (ITT) populations were extracted or reconstructed from Kaplan-Meier curves when not reported as inputs for Bayesian fixed-effects NMAs.Comparative effectiveness was reported using median HR and 95% credible intervals (CrIs).Results: Trials reporting ITT populations were included, resulting in 9 trials (6663 pts) for PFS analysis and 10 trials (6735 pts) for OS analysis representing 8 regimens.Pts were randomly assigned to an experimental arm vs FOLFOX/CAPOX.Pts on 1L zolbetuximab, nivolumab, or pembrolizumab in combination with CF/CAPOX or FOLFOX/ CAPOX had significantly reduced risk of disease progression or death vs FOLFOX/CAPOX (Table). Zolbetuximab + FOLFOX/CAPOX had the highest probability of being ranked first in treatment efficacy for both PFS (probability =0.54) and OS (0.36); followed by pembrolizumab + CX (0.27) and pembrolizumab + CF/CAPOX (0.13) for PFS; and by pembrolizumab + CF/CAPOX (0.3) and nivolumab + FOLFOX/CAPOX (0.24) for OS. Conclusions: This NMA examined the relative benefit of different targeted therapies when combined with chemotherapy. Zolbetuximab + FOLFOX/ CAPOX for CLDN18.2+, HER22, LA unresectable or mG/GEJ adenocarcinoma confers a significant PFS and OS benefit, similar to that achieved with PD-1/PD-L1 inhibitors + CF/CAPOX or FOLFOX/CAPOX. Research Sponsor: Astellas Pharma Inc.

the 12 patients enrolled in cohort E (median age [range]: 64.5[53] [54][55] [56][57] [58][59] [60][61] [62][63] [64][65] [66][67] [68][69] [70][71] years, PS 0/1: 12/0, clinical stage I/II/III/IVA: 4/5/3/0), 4 developed DLT (grade 3 mucositis, erythema multiforme, and pneumonitis, n=1 each; grade 5 pneumonitis, n=1), which was within the prespecified range of safety (n # 4). Other grades$3 adverse events were neutropenia (n=7), leukopenia (n=6), fever, fatigue, febrile neutropenia, rash, elevated amylase, elevated hepatic enzyme, hypotension, and thrombocytopenia (n=1 each) during FLOT + Nivo, and anastomotic leakage (n=1) during the postoperative period. One patient discontinued FLOT + Nivo due to DLT of erythema multiforme, eleven patients (91.7%) completed the protocol treatment and R0 resection rate achieved 91.7% (11/12). In cohort E, the objective response rate in patients with measurable lesion was 0% (0/4). However, 5 patients (41.7%) achieved a pathological complete response, and 6 (50.0%) achieved a pathological complete response in primary tumors among 12 patients. Conclusions: Neoadjuvant FLOT + Nivo followed by surgery for locally advanced ESCC was tolerated and showed promising efficacy. Clinical trial information: NCT03914443. Research Sponsor: Ono Pharmaceutical Co., Ltd.

pts), fluoropyrimidine plus platinum (2 pts) and 1 pt continued Nivo+Ipi beyond progression.Conclusions: Our study may demonstrate a consistent incident of irAEs in pts who received Nivo+Ipi in the real world, compared to the results of the CheckMate 648.Despite of the short time of follow-up period, 1st-line treatment with Nivo+Ipi appeared to be more efficacious than Nivo+Ipi used as a laterline treatment.Research Sponsor: None.Tislelizumab plus chemotherapy (chemo) versus placebo plus chemo as first-line treatment for locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma: RATIONALE-305 European/ North American patient subgroup. First Author: Hendrik-Tobias Arkenau, Sarah Cannon Research, London, United Kingdom Background: Tislelizumab (TIS), an anti-programmed cell death protein 1 monoclonal antibody, plus chemo, demonstrated significant overall survival (OS) benefit vs placebo (PBO) plus chemo (15.0 vs 12.9 months [mo], hazard ratio [HR] =0.80, 95% confidence interval [CI]: 0.70, 0.92, P=0.0011) as first-line therapy in patients (pts) with advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC) in the randomized, double-blind, global, phase 3 RATIONALE-305 study (NCT03777657). Here we present results from the European/North American (Eu/NA) pts subgroup analysis. Methods: This double-blind, global, phase 3 study evaluated adult pts with previously untreated, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced unresectable, or metastatic GC/GEJC, regardless of programmed death-ligand 1 (PD-L1) expression status. Eligible pts were randomized (1:1) to receive TIS 200 mg or PBO intravenously once every 3 weeks plus investigator chosen chemo (5-fluorouracil + cisplatin or capecitabine + oxaliplatin). The primary endpoint was OS in the PD-L1+ (patients with tumor area positivity score $5%) and intent-to-treat (ITT) analysis sets. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), and safety. Results: Of 997 pts enrolled, 249 (25.0%) were from Eu/NA (TIS plus chemo arm, n=125; PBO plus chemo arm, n=124). In the Eu/ NA pts subgroup, after a minimum follow-up of 26.6 mo at final analysis, TIS plus chemo resulted in OS improvements vs PBO plus chemo in the PD-L1+ (HR=0.75, [95% CI: 0.52, 1.07]; 24 mo rate 27.6% vs 12.5%) and ITT analysis sets (HR=0.71, [95% CI: 0.54, 0.94]; 24 mo rate 27.6% vs 13.6%). TIS plus chemo resulted in favorable PFS vs PBO plus chemo (HR=0.84, 95% CI: 0.63, 1.11), numerically higher ORR (36.0% vs 31.5%), and longer DoR (median 7.5 mo [95% CI: 4.4, 12.0] vs 5.0 mo [95% CI: 3.9, 6.7] ). Sixty (48.8%) pts in the TIS plus chemo arm and 61 (49.2%) pts in the PBO plus chemo arm experienced grade $3 treatment-related treatment-emergent adverse events (TRAEs). Sixteen (13.0%) and seven (5.6%) pts discontinued treatment due to TRAEs in the TIS plus chemo and PBO plus chemo arms, respectively. Deaths due to TRAEs occurred in two (1.6%) pts in the TIS plus chemo arm and one (0.8%) pt in the PBO plus chemo arm.

). OS at 5-year were 82.1% and 85.0% in the late and reference groups, respectively.In the multivariable analysis, DFS in the late group retained inferiority (aHR 1.138, 95% CI: 1.003-1.292,p=0.045).OS showed a worse trend without significance compared to the reference group (aHR 1.138, 95% CI: 0.984-1.317,p=0.0805).Conclusions: Adjuvant chemotherapy after gastrectomy in patients with gastric cancer should be initiated within five weeks of surgery.A delay of more than five weeks may have a detrimental effect on the subsequent disease course.Research Sponsor: National Research Foundation of Korea (NRF) grant funded by the Korean Government (MSIT); 2021R1F1A1061156.Impact of adding nivolumab to first-line chemotherapy in patients with advanced gastric cancer.First Author: Mai Utsumi, Osaka Medical and Pharmaceutical University Hospital, Takatsuki, Japan Background: Nivolumab plus chemotherapy (Nivo-Chemo) is the standard treatment for advanced gastric cancer based on the results of CheckMate 649 trial and ATTRACTION-4 trial.However, real-world data on the efficacy of Nivo-Chemo are limited.This study aimed to assess the efficacy of Nivo-Chemo in the clinical practice setting by comparing it to chemotherapy alone.Methods: We retrospectively reviewed the medical records of patients with advanced gastric cancer who received palliative chemotherapy in our hospital between 2017 and 2023.The inclusion criteria were as follows: age $ 20 years; histologically confirmed advanced unresectable or recurrent gastric/gastro-esophageal junction adenocarcinoma; HER2 negative or unknown; and no prior treatment.Patients were divided into two groups based on their first-line treatment: the Nivo-Chemo group and chemotherapy alone (Chemo) group.Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) were assessed.Results: Of 78 patients, 52 patients were in the Chemo group and 26 patients were in the Nivo-Chemo group.Median age were 69 years (range 30-83) and 67 years (range 39-76) in the Chemo group and Nivo-Chemo group.Eastern Cooperative Oncology Group performance status (ECOG PS) was 0/1/2 in 18/27/7 patients (35%/52%/13%) in the Chemo group and in 17/8/1 patients (65%/31%/4%) in the Nivo-Chemo group.Histological type (Intestinal type/diffuse type) was 19/33 (37%/63%) in the Chemo group and 8/18 (31%/69%) in the Nivo-Chemo group.Combined positive score (CPS) was assessed in 21 patients in the Nivo-Chemo group.The CPS ,1/1-5/.5 was in 3/10/8 (12%/38%/ 31%).In the Chemo group, 28 patients (54%) received anti-PD-1 monotherapy after progression of first-line chemotherapy.The median PFS was 5.7 months in the Chemo group and 6.0 months in the Nivo-Chemo group (HR 0.88, 95% CI 0.50-1.55,p=0.66).The median OS was 15.0 months in the Chemo group and 18.6 months in the Nivo-Chemo group (HR 0.76, 95% CI 0.37-1.53,p=0.44).The ORR was 50% in the Chemo group and 54% in the Nivo-Chemo group, while the DCR was 63% and 69%, respectively. Conclusions:In clinical practice, the addition of nivolumab to chemotherapy tended to provide a survival benefit compared to chemotherapy alone.Research Sponsor: None.The primary objective of phase Ib was to determine the DLT in first treatment cycle defining the PR2D.Additional 64 pts were enrolled in the phase II dose expansion stage using RP2D.Primary endpoint of phase II was PFS per RECIST 1.1.Secondary endpoints included ORR, DCR, OS, DOR and safety.Results: At data cut-off (August 31, 2023), 17 pts (9 in phase Ib; 8 in phase II) with median age 65 years old had been enrolled.59%weremale,100%hadECOG PS 1 and 35% had liver metastasis.10/17(59%)ptswerePD-L1CPS $1.No DLTs were observed at all three dose levels.This study included 911 patients who underwent APC for gastric neoplasms at the tertiary hospital from July 2007 to March 2022 with a minimal follow-up of 12 months.112subjectswithoutanyinformationabout H. pylori infection status, 164 subjects who underwent APC for salvage therapy, 5 subjects with high grade dysplasia, and 12 subjects with cancer were excluded.Through a retrospective review of medical data, the clinical outcomes and variables associated with the local recurrence were analyzed.Results:A total of 618 patients with LGD (median age of 64 years old) were followed up for a median of 30 months and local recurrence has happened in 21 patients (3.4%). The detection of ctDNA in patients with colorectal cancer (CRC) is emerging as a potential biomarker to identify patients at high risk of relapse, assess treatment response and monitor for recurrence.Solid tumors are currently monitored by imaging studies, tumor markers and clinical symptoms and recent studies suggest tumor-informed molecular residual disease (MRD) testing may outperform these current methods and may serve as a prognostic biomarker to aid in the identification of patients at high risk of relapse(Reinert et al, 2019; Christensen et al, 2019; Coombes et al, 2019).Recent studies have demonstrated that tumor-informed MRD testing can detect relapse prior to detection with imaging in CRC and while interventional trials are needed, this may provide an opportunity for therapeutic intervention(Reinert et al, 2019; Kotani et al, 2023).This study utilizes the Invitae Personalized MonitoringTM (PCM) test, a highly sensitive tumor-informed MRD test(Zhao et al, 2023), to monitor early stage CRC patients. Methods: MARIA is a multi-site, prospective, observational trial in the United States of 200 newly diagnosed patients with early stage (high risk stage II, stage III and stage IV oligometastases) CRC undergoing curative intent treatment. Formalin fixed paraffin embedded (FFPE) tissue from the biopsy or surgical specimen is utilized to create the PCM test. Tumor tissue and a matched normal blood sample will undergo whole exome sequencing to identify 18-50 unique tumor variants to create a patient specific panel (PSP) for ctDNA analysis. Participants are asked to provide serial plasma specimens for ctDNA analysis at baseline, post surgical landmark and surveillance time points. A clinical report will be provided to the ordering physician. Physicians will be asked to complete a case report form for each participant when the first result is reported and every 6 months. The primary endpoint is to evaluate the correlation between the PCM test result at the landmark timepoint and the patient's 24 month

Inhibition of TIGIT, a novel checkpoint inhibitor, may further amplify immune responses by complementing the PD-L1/PD-1 pathway.Anti-tumor activity has been demonstrated with cancer immunotherapy in ESCC.SKYSCRAPER-08 (NCT04540211) is evaluating the efficacy and safety of tira (anti-TIGIT) + atezo (anti-PD-L1) in combination with CT compared with placebo + CT as 1L treatment (tx) in an Asian population with unresectable locally advanced (LA), unresectable recurrent, or metastatic (R/M) ESCC.Methods: Eligible pts (confirmed LA or R/M ESCC; ECOG PS 0-1; no prior systemic tx) were randomized 1:1 to receive tira 600mg + atezo 1200mg + CT (paclitaxel 175mg/m2 + cisplatin 60-80mg/ m2, local standard of care) or placebo + CT on Day 1 of each 21-day cycle (cycles 1-6); followed by tira + atezo or placebo maintenance until loss of clinical benefit/unacceptable toxicity.Primary endpoints: independent review facility (IRF)-assessed progression-free survival (PFS) and overall survival (OS).Secondary endpoints: investigator (INV)-assessed PFS, objective response rate (ORR), duration of response (DoR), and safety.Results: Overall, 461 pts were randomized (tira + atezo + CT, n= 229; placebo + CT, n=232).Pt characteristics were generally balanced between arms.As of 15 June 2022 (minimum survival follow-up 6.5 months[mo]; PFS primary analysis), median IRF-assessed PFS was 6.2 mo for tira + atezo + CT vs 5.4 mo for placebo + CT (HR 0.56; 95% CI: 0.45, 0.70; P,0.0001).As of 13 Feb 2023 (minimum survival follow-up 14.5 mo; OS final analysis), median OS was 15.7 mo for tira + atezo + CT vs 11.1 mo for placebo + CT (HR: 0.70; 95% CI: 0.55, 0.88; P= 0.0024).INV-assessed PFS, IRF-assessed ORR and DoR are presented in Table.Treatment-related adverse events (TRAEs) occurred in 98.2% of pts (both arms); Grade 3/4 TRAEs in 59.6% (tira + atezo + CT) and 56.4% (placebo + CT) of pts; Grade 5 TRAEs in 2.6% (tira + atezo + CT) and 0.9% (placebo + CT) of pts. Conclusions: The study met both primary endpoints of IRF-assessed PFS and OS, demonstrating statistically significant and clinically meaningful improvements in PFS and OS for tira + atezo + CT over placebo + CT. Generally consistent benefit was observed across subgroups, including PD-L1 status. The safety profile was consistent with the known risks of the individual tx. Clinical trial information: NCT04540211. Research Sponsor: F. Hoffmann-La Roche Ltd/Genentech Inc.

44, the predefined non-inferiority margin. Results: We randomized 300 patients, assigning 150 to the TE group and 150 to the OE group between May 2015 and June 2022. The second planned interim analysis with 64 OS events was conducted in June 2023. Median follow-up (interquartile range) was 2.6 (1.4-4.9) years. Three-year OS was 82.0% (95% CI, 73.8%-87.8%) in the TE group, and 70.9% (61.6%-78.4%) in the OE group. The Data and Safety Monitoring Committee recommended terminating the trial and publishing the results

Conclusions: These results further support the clinical efficacy of NIVO + chemo and NIVO + IPI in 1L ESCC and suggest enhanced OS benefit in multiple biomarker subgroups.The clinical utility of these biomarkers should be validated in future trials.Clinical trial information: NCT03143153.Research Sponsor: Bristol Myers Squibb.Disparities in survival in Asian American, Native Hawaiian, and Pacific Islander patients with gastric adenocarcinoma: An NCDB analysis. First Author: Anjali Mishra, Creighton University School of Medicine, Omaha, NE Background: Asian American, Native Hawaiian, and Pacific Islander (AANHPI) individuals exhibit stark disparities in gastric cancer mortality rates, with AANHPI men facing a two-fold higher risk of death and AANHPI women encountering a 2.5-fold elevated risk compared to their Non-Hispanic White (NHW) counterparts. However, the AANHPI community is a diverse group, including over 21 ethnic groups. Here, we identify disparities among AANHPI subpopulations with gastric adenocarcinoma. Methods: Using the National Cancer Database, which gathers data from over 1,500 accredited hospitals and facilities across the United States, this retrospective cohort study identified 141,906 patients with gastric adenocarcinoma (ICD code "8140"). Races listed as "unknown/other" or "Other Asian" were excluded. Kaplan Meier and Cox Regression model were performed. Results: This study compared mean overall survival (OS) of NHW (n=111,137), East Asian (EA) (n=3,745), South Asian (SA) (n=760), Southeast Asian (SEA) (n=1,379), and Native Hawaiian or Pacific Islander (NHPI) (n=325) patients with gastric adenocarcinoma. When aggregated, AANHPI had statistically significant improved OS compared to NHW (21.6 months vs 14.1 months, p , 0.001). After disaggregating, the mean OS was 26.9 months for EA; 21.3 months for SA; 14.5 months for SEA; and 14.3 months for NHPI. Only SA and EA had significantly improved OS than NHW (p,0.001 for both). SEA and NHPI had significantly worse outcomes than EA (p,0.001 for both) and SA (p,0.001 for SEA, and p = 0.033 for NHPI). Multivariate analysis accounted for age at diagnosis, insurance status, median income quartile, Charlson-Deyo comorbidity score, facility type, stage at diagnosis, and time to treatment. SA (HR=0.82; 95% CI, 0.726 to 0.925; p,0.001)), EA (HR=0.644; 95% Gastric cancer accounts for approximately 1.5% of all new cancers diagnosed in the US, with a high incidence in older White populations. However, this study demonstrates that there is a large proportion of young Hispanics with gastric cancer who have higher associated instances of H. pylori. This suggests the need for further research to determine if there is utility in screening for H. pylori in asymptomatic young Hispanics to decrease the burden of gastric cancer in this population. Research Sponsor: None.

Differential burdens: A study of gastric cancer hospitalization and outcomes across race and ethnicities.First Author: Chun-Wei Pan, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL Background: Despite advances in H. pylori screening and eradication, gastric cancer remains a significant public health issue as the 4th most common cancer globally.Racial and ethnic disparities in disease presentation, surgical intervention, and healthcare burden in United States are not well understood.Methods: We retrospectively analyzed National Inpatient Sample data (2016-2020) for gastric cancer hospitalizations in patients $18 years.Primary outcome was in-hospital mortality.Secondary outcomes included disparities in gastrectomy, length of stay (LOS), and total hospital charges.Results: In our study, we analyzed 207,690 hospitalizations related to gastric cancer from 2016-2019.Over this period, we observed a decrease in gastric cancer-related hospitalizations, from 42,865 to 39,855.However, among Hispanics, there was a significant increase in hospitalizations from 6,309 to 6,930 cases (annual percentage change [APC] of 1.89%, P,0.01).Notably, there was a significant higher in in-hospital mortality odds for African-American (AA) (aOR 1.15, 95CI: 1.03-1.29),Asian(aOR 1.23, 95CI: 1.06-1.42),andall other races (aOR 1.35, 95CI: 1.13-1.60).Surgical interventions differed among racial groups, with AA having lower odds of undergoing total gastrectomy (aOR 0.71, 95CI: 0.60-0.86),andAsians having higher odds of receiving partial gastrectomy (aOR 1.59, 95CI: 1.41-1.78).LOS also differs between ethnicities, AA had the highest LOS 7.960.1ddays,followed by Native American/Other (NA) at 7.560.2days.The financial impact of also differs, with Asians incurring the highest mean total charges at 101,436.863,253.5,followedby NA at 93,102.763,954.7.The total hospital charge burden of gastric cancer increased from 3,682.8 million to 3,880.0 million (APC 1.04%).The white population experienced the highest increase in this burden, from 1,879.2 million to 1,990.0 million (APC of 1.10%).Conclusions: Despite an overall decrease in gastric cancer hospitalizations, our study reveals notable disparities across racial and ethnic groups.Hospitalizations increased among Hispanics, and AA, Asians, and NA faced higher mortality odds.AA experienced the longest lengths of stay, while Asians bore the highest mean total charges.These findings highlight the need for targeted interventions to mitigate these disparities.Research Sponsor: None.Unveiling survival strategies: The impact of treatment modalities on patients with esophageal cancer and the role of racial disparities.First Author: Dani Ran Castillo, City of Hope National Cancer Center, Duarte, CA Background: Managing esophageal cancer (EC) involves neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy as the standard of care.However, some patients may remain unsuitable for esophagectomy.This study explores real-world outcomes in EC patients across different treatments, considers prognostic factors, and examines potential racial disparities.Methods: Data from 44,181 patients diagnosed with locally advanced EC between 2004-2017 were extracted from the National Cancer Database.The cohort was stratified into three groups: nCRT followed by esophagectomy, definitive RT (dCRT), single-modality RT.The dataset included 24,676 patients who received nCRT with esophagectomy or dCRT (N=17,534) and 1,971 patients who received single-modality RT.Endpoints included overall survival (OS).Cox Proportional Hazards Model was employed for multivariate survival analysis.Chi-square test was applied to the covariate demographic data.Results: nCRT followed by esophagectomy significantly improved OS compared to dCRT (mOS 43.5 vs. 20.1 months, p , 0.001).Single-modality RT had an mOS of 14.4 months.In the RT group, 73% were over 65 years old compared to 59% in the dCRT group (p , 0.001).Over 60% of patients had node-positive disease in both RT and dCRT groups (69% vs. 61.4%).More privately insured patients received multimodal treatment compared to publicly insured patients (27.3% vs. 16.8%,p , 0.001).Over 70% of patients were willing to travel within 20 miles for treatment, 60% underwent treatment in community programs.Racial disparities were observed, with Black patients experiencing worse outcomes compared to all other groups, while Asian and Hispanic patients had better outcomes (table1).In the squamous cell histology subset treated with dCRT, mOS was 22 (20.6 -23.6 months) for Black patients, 27 (26 -28) months for White patients, 36 (30-46) months for Hispanic patients, and 37 (30-44) months for Asian/Pacific Islander patients (p , 0.001).Conclusions: This real-world data analysis underscores the effectiveness of nCRT followed by esophagectomy in providing the best survival benefit for EC patients compared to dCRT or RT alone.Racial disparities emerged as significant factors influencing cancer survival outcomes.These identified factors including race and age can assist clinicians in making better-informed decisions regarding treatment pathways for specific patient populations.Research Sponsor: None.Hispanics were less likely to have surgical intervention (20.5% vs 27.5%) p,0.001, receive neoadjuvant therapy (61.8% vs 72%) and overall, less likely to receive any type of treatment (30.1% vs 26.1%) when compared to NH p,0.001.Time to treatment was delayed in those Hispanics who were uninsured 37 weeks

). Results: PredicineCARE ULTRA cfDNA assay exhibited exceptional sensitivity in calling single-nucleotide variants and indels, with a 98.0% detection rate at a LoD of 0.075% mutant allele frequency (MAF) for 60 ng cfDNA.This is significantly lower than the LoD (0.25% MAF) of a standard PredicineCARE cfDNA assay.The ultra-sensitive assay also displayed decent analytical specificity (.99.99%) and precision (intra-assay 100%; inter-assay 99.41%).In 6 GEC patients' longitudinal samples, PredicineCARE ULTRA cfDNA assay detected 36 additional somatic mutations with the MAFs spanning in a range from 0.024% to 0.1% beyond 124 baseline mutations identified using standard PredicineCARE.In two representative cases presented here, all baseline mutations (genes TP53 and PIK3CA etc.)Efficacy and safety of trastuzumab deruxtecan and nivolumab as third-or later-line treatment for HER2-positive advanced gastric cancer: A singleinstitution retrospective study. First Author: Keitaro Shimozaki, Department of Gastrointestinal Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan Background: Despite the difficulty of directly comparing trastuzumab deruxtecan (T-DXd) and nivolumab as third-or later-line treatment for HER2-positive advanced gastric cancer (AGC) in randomized trials, discussions regarding optimal treatment strategies are desired. Methods: This single-institution retrospective study aimed to describe the real-world efficacy and safety of T-DXd and nivolumab as third-or later-line treatment for patients with HER2-positive AGC treated between March 2016 and May 2022. DXd and nivolumab had distinctive efficacy and toxicity profiles as third-or later-line treatment for HER2-positive AGC. Considering the distinct features of each regimen might help clinicians personalize the optimal treatment approaches for patients with HER2-positive AGC. Research Sponsor: None.

Patients with non-curative resection factors limited to positive peritoneal cytology, or those who relapsed during adjuvant chemotherapy or within 6 months after its completion, were excluded.Results: Out of the total 825 patients, 765 had GA and 60 had EGJA.The baseline characteristics of the GA and EGJA Impact of time-of-day on nivolumab monotherapy infusion in patients with metastatic gastric cancer.First Author: Yasunobu Ishizuka, Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan Background: Nivolumab monotherapy, an immune checkpoint inhibitor, is a standard of care for patients with metastatic gastric cancer (mGC) as a later-line treatment.Several studies have suggested that the circadian rhythm is essential in immune system function, including anti-cancer immunity.This study evaluated whether the time-of-day patterns of nivolumab infusion alter the efficacy of mGC treatment.Methods: This study retrospectively analyzed 298 consecutive mGC patients who received nivolumab monotherapy at a single institution between December 2014 and December 2022.Multivariate analyses, including factors such as age, ECOG performance status, histological type, ascites, modified Glasgow Prognostic Score, and timing of nivolumab infusion, showed that EA was an independent prognostic factor for PFS (adjusted HR, 0.66; P,0.01) and OS (adjusted HR, 0.62; P,0.01).Conclusions: Our data suggest that efforts to schedule nivolumab infusions before mid-afternoon could be considered in daily practice.Research Sponsor: None.Recurrence-free survival as a surrogate for overall survival in esophageal squamous cell carcinoma: Nationwide real-world data from Japan. First Author: Jun Okui, Department of Surgery, Keio University School of Medicine, Tokyo, Japan Background: One of the limitations of the established gold standard, overall survival (OS), is that it requires an extended follow-up period. Addressing this challenge involves investigating appropriate statistically and clinically relevant surrogate endpoints. However, there is a paucity of studies using real-world data (RWD) to explore surrogacy in patients with esophageal squamous cell carcinoma (ESCC). Our study aims to investigate whether recurrence-free survival (RFS) is a valid surrogate endpoint for OS in surgically resectable advanced ESCC patients, utilizing a comprehensive nationwide database in Japan. Methods: The ESCC patients who received neoadjuvant CF (cisplatin and 5-fluorouracil) or DCF (docetaxel, cisplatin and 5-fluorouracil) at 58 Japanese esophageal centers certified by the Japan Esophageal Society were retrospectively reviewed. Kendall's tau between RFS and OS was used at the individual level, and the coefficient of determination was used at the institutional level to assess surrogacy. This study retrospectively examined RGC patients who received gastrectomy with #10 nodal dissection after distal gastrectomy at two high-volume cancer centers in Japan between 1998 and 2015. Results: 99 patients were entered in this study. The #10 nodal metastatic rate was 12.1% (12/99). Initial gastrectomy was performed for benign in 42 patients and for malignant in 52 patients. The median duration from the initial gastrectomy was 20 (1-55) years. Main tumor location was lesser curvature in 46 patients, anterior wall in 11, greater curvature in 19, posterior wall in 11, and the whole in 12. We retrospectively reviewed medical records of patients who received adjuvant nivolumab after neoadjuvant DCF and surgery for locally advanced ESCC from Nov 2021 to Jun 2023 at National Cancer Center Hospital East. Pathological stage was classified by UICC-TNM 8 th edition. Adverse events were assessed according to CTCAE v5.0. Disease-free survival (DFS) was calculated by Kaplan-Meier method. Results: The study included a total of 33 patients with a median age of 67 years (range, 56-77), of which 29 patients were male. All patients had residual pathological disease, with ypStage I/II/III/IV of 5/1/16/11 patients. Median time from surgery to the initiation of adjuvant nivolumab was 10.6 weeks (range, 7.1-16.4 weeks).

Correlation between histopathological response by neoadjuvant DCF therapy and the clinical efficacy of palliative platinum-containing regimens for recurrent ESCC. First Author: Shota Igaue, Department of Esophageal Surgery, National Cancer Center Hospital, Tokyo, Japan Background: Docetaxel and cisplatin, 5-FU (DCF) therapy has established as the standard neoadjuvant treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC) based on the results of the JCOG1109 study. If patients showed recurrence of ESCC after neoadjuvant DCF therapy, platinum-containing regimens were used as palliative treatment in the clinical practice. However, there were no data of correlation between histopathological response by neoadjuvant DCF therapy and clinical efficacy of palliative platinum-containing regimens for recurrent ESCC.

Assessment of circulating tumor DNA (ctDNA) burden and association with outcomes in metastatic gastric cancer (mGC) patients using real-world data (RWD).First Author: Senaka A. Peter, Merck & Co., Inc., Rahway, NJ Background: CtDNA burden has been shown to have potential uses in early cancer detection, guiding treatment decisions, residual disease and drug resistance detection, and treatment response monitoring.While published literature suggested that ctDNA may be prognostic of clinical outcomes for various tumor types, there is limited RWD assessing its use in mGC.This study uses RWD to evaluate the association of pre-treatment ctDNA burden with clinical outcomes in mGC.Methods: Patients were identified from the Guardant INFORM real-world clinical-genomic database, which links ctDNA results via plasma-based next-generation sequencing Guardant360 assay (G360) to de-identified claims data.Adult mGC patients in the US, who received NCCN guideline treatments post-diagnosis and underwent testing with G360 from June 2014 to March 2022 were included.For those who received first line (1L) therapy within 60 days after a G360 test result, median of the maximum variant allele fraction (mVAF) was used to classify them into high or low ctDNA burden groups, with undetectable ctDNA burden considered low.Associations with time to next treatment (TTNT) and overall survival (OS) were assessed using log rank tests and multivariable Cox proportion hazards models adjusting for age, sex, Elixhauser comorbidity score, and anatomical location.Results: 2,200 mGC patients were identified, of which 824 (37%) initiated 1L therapy within 60 days after a G360 test.Among the 824 patients, mean age was 63 years, 70% were male and 47% had gastric adenocarcinoma and 53% gastroesophageal junction cancer.Median mVAF among these patients was 2.9%, with 91% having detectable ctDNA.Patients with high ctDNA burden treated with 1L chemotherapy (Chemo) showed significantly worse TTNT and OS than low ctDNA burden patients (Median TTNT= 4.7 months vs 7.5 months, p,0.001;MedianOS=12.4months vs 19.1 months, p,0.001).Multivariable Cox analyses showed similar results for 1L Chemo group.Treatment group outcomes based on adjusted Cox models were reported (Table).Conclusions: We used RWD to demonstrate that high pre-treatment ctDNA burden was associated with worse clinical outcomes in a mGC population treated with 1L Chemo.Our analysis adds to the body of evidence that suggest ctDNA burden could be used as a prognostic biomarker for mGC.The small sample size of the other 1L treatment groups warrants further investigation because the use of IO-based therapy is expected to increase with recent approvals.Research Sponsor: None.Helicobacter pylori infection and response of gastric cancer to immunotherapy. First Author: Yinghong Wang, The University of Texas MD Anderson Cancer Center, Houston, TX Background: Helicobacter pylori is a known risk factor for gastric cancer, possibly via the PD-1/L1 pathway. Some suggest that H. pylori infection may counteract the action of immune checkpoint inhibitors in few studies with limited sample size. This study explores the effects of H. pylori infection status on survival outcomes in patients with gastric cancer. Methods: This single-center, retrospective chart review included patients with gastric adenocarcinoma between June 1985 and August 2022. Patients with different histological subtypes were excluded. Primary variables of interest included H. pylori infection status and treatment with ICIs. Other clinical information included demographics, cancer histology, the presence of other cancers, and vital status. Conclusions: H. pylori infection may negatively impact the therapeutic effect of ICIs. These findings suggest H. pylori infection may be an obstacle to successful immunotherapy and may interact with cancer subtypes to differentially impact survival. Future studies are needed to validate the potential prognostic value of H. pylori positivity in gastric cancer. Research Sponsor: None.

First-line FOLFOX therapy for advanced esophageal squamous cell carcinoma: Multicenter prospective study in Japan. First Author: Kunihiro Fushiki, Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan Background: Cisplatin (CDDP) plus fluoropyrimidine was the standard first-line treatment in patients with advanced esophageal squamous cell carcinoma (ESCC). FOLFOX is promising option especially in patients with ESCC intolerant to CDDP but there were limited data on efficacy and safety of FOLFOX. We conducted a multicenter prospective observational study of FOLFOX for Japanese patients with ESCC intolerant to CDDP. Methods: Eligible participants had clinical stage IVB ESCC, with measurable Clinical outcomes of conversion surgery following immune checkpoint inhibitors and chemotherapy in stage IV gastric cancer with peritoneal metastasis. First Author: Huayuan Liang, Department of General Surgery, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China Background: Although anti-PD-1 antibody in combination with chemotherapy and/or targeted therapy has shown promising antitumor activity in advanced gastric adenocarcinoma (GC), the evidence of conversion therapy for initially GC with peritoneal metastasis is limited. This study aimed to clarify the clinical outcomes of conversion therapy for such patients. Methods: In this retrospective single institution cohort study, we analyzed 83 GC patients with peritoneal metastasis who received first-line anti-PD-1 antibody and chemotherapy and/or target therapy (trastuzumab) between November 2019 and June 2023. In patients who respond well to treatment, when preoperative imaging studies, multidisciplinary team discussions, and staged laparoscopy indicated the absence of peritoneal metastasis and the possibility of R0 resection, patients were offered conversion surgery. In this study, palliative surgery was not included. Patients were divided into two groups: conversion therapy group and palliative therapy group. Results: All patients underwent staging laparoscopy at their initial visit and underwent at least 2 treatment cycle, with a median follow-up time of 20.3 (16-24.6) months. Of the 83 patients, 32 patients presented a clinical response and underwent re-laparoscopy. Negative peritoneal metastasis and peritoneal cytology were confirmed in 25 patients who proceeded to undergo the conversion surgery. Compared with palliative therapy group, surgery group had a significantly better PFS2) systemic therapy and disease-free interval (DFI) in the recurrent group (defined as time between initial diagnosis and development of recurrent disease). OS was calculated from diagnosis of stage IV disease. Cox proportional hazards and Kaplan Meier curves were used to compare OS, PFS1 and PFS2. Outcomes were adjusted for baseline characteristics. The effect of DFI on outcomes was evaluated in the recurrent group.

Short-term and long-term results of robot-assisted esophagectomy in cT3br/T4b esophageal cancer at initial diagnosis: Comparison with conventional thoracoscopic surgery.First Author: Takeo Fujita, Division of Esophageal Surgery, National Cancer Center Hospital East, Kashiwa, Japan Background: Conversion surgery in patients with locally advanced esophageal cancer that is not resectable at first time and has responded to prior therapy remains unclear.Recently, the usefulness of RAMIE for locally advanced esophageal cancer has begun to be discussed.In this study, we first analyzed the short-and long-term results of RAMIE, then examined the results of conversion RAMIE in T3br/T4b patients, and compared them with those of conversion using conventional MIE.T4b cases in the usual MIE showed a favorable trend in RAMIE (p=002).Of the 38 patients with recurrence after RAMIE surgery, 19 were local/regional and 19 were distant.Of these, 5/6/5/3 were brain/lung/liver/LN+others as the first site of distant metastasis.Conclusions: The short-and long-term results of RAMIE in our department, including T3br/T4, were described, and the short-term and long-term results of RAMIE were considered acceptable.In terms of recurrence, local/regional disease control was considered to be relatively good.Research Sponsor: None.Prognostic impact of ectopic fat deposition within psoas muscle in patients undergoing systemic chemotherapy for stage IV gastric cancer.First Author: Takako Ikegami, The Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Japan Background: Sarcopenia is a progressive condition characterized by loss of skeletal muscle mass, muscle strength, and physical function, and is identified as an important prognostic factor in malignant tumors.The patients of gastrointestinal (GI) malignancies are often poor nutrition, weight loss, and loss of skeletal muscle mass due to pathophysiology such as the dysfunction of nutritional absorption and GI obstruction.The prevalence of sarcopenia is high in GI malignancies, especially in advanced gastric cancer (GC), which is reported to be 30%.Recently, in assessing sarcopenia, muscle quality as well as skeletal muscle mass has been considered important and some studies suggest that intramuscular adipose tissue is useful in assessing muscle quality.In this study, we focused on the fat ratio within psoas muscle (FRPM) and sought to clarify the impact of FRPM on overall survival (OS) in GC patients undergoing systemic chemotherapy.Methods: We retrospectively analyzed the patients with histologically confirmed stage IV GC receiving at least one systemic chemotherapy between February 2017 and March 2021 in our hospital.We measured PMI (Psoas Muscle Index: bilateral muscle mass (cm 2 )/height squared(m 2 )) and FRPM both at the lumber three level on the CT images before chemotherapy.PMI and FRPM values were classified into two groups, High and Low, according to whether they were higher or lower than the median, and differences in OS were analyzed for each group.Results: The analysis included 79patients (median age: 69 years, 59 males).The median FRPM was 1.67%.The FRPMhigh group and the FRPM-low group were 40/39patients, respectively.The median PMI in male and female patients was 4.35 cm 2 /m 2 and 2.88 cm 2 /m 2 .Thirty male patients and ten female patients were defined as the PMI-high group, and the remaining 39 patients were in the PMI-low group.The 1, 2 and 3year cumulative OS rate in patients with FRPMhigh and FRPM-low was 67.3%, 14.3% and 7.6% in the FRPM-high group and 74.8%, 40.5% and 32.4% in the FRPM-low group (P = 0.0341).The 1, 2 and 3year cumulative OS rate in patients with PMI-high and PMI-low was 86.7%, 40.4% and 30.0% in the PMI-high group and 55.End points were least squares mean (LSM) change from baseline, time to deterioration (TTD), and overall improvement/stability rate in prespecified subscales of EORTC QLQ-C30, QLQ-STO22, EuroQol EQ-5D-5L.LSM changes from baseline were analyzed at wk 24 when prespecified completion and compliance rates of ~60% and 80%, respectively, were met, based on review of blinded data. Results: In the PRO analyses, 685 pts were evaluable (345 pembro with tras + chemo; 340 pbo with tras + chemo).Median time from randomization to data cutoff (May 25, 2022) was 28.4 mo (range, 9.3-42.6).Completion rates were .92% at baseline and .55% at wk 24 for all assessments in both arms.Similar changes in PRO scores from baseline to wk 24 were observed for the pembro versus pbo arms (Table). Similar percentages of pts in each arm had improved or stable scores for the EORTC QLQ-C30 GHS/QOL and physical functioning scales and EORTC QLQ-STO22 subscales. TTD was similar between arms for all prespecified subscales.

An observational study on treatment patterns and outcomes among patients with metastatic or recurrent esophageal cancer: Real-world data and empirical analyses in Japan (POME).First Author: Shun Yamamoto, Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan Background: There has been little information on treatment patterns and factors affecting outcomes of metastatic or recurrent esophageal cancer (EC) in clinical practice before the marketing of immune checkpoint inhibitors.This study aimed to investigate the treatment patterns and outcomes among patients (pts) with EC treated with systemic chemotherapy (CTx).Methods: This was a retrospective chart review study and included pts with his-GC/GEJC): Health-related quality of life(HRQoL)outcomes in the RATIONALE-305 study.First Author: Marcia Cruz-Correa, University of Puerto Rico, School of Medicine, San Juan, Puerto Rico Background: RATIONALE-305 (NCT03777657), demonstrated statistically significant and clinically meaningful improvements in overall survival (OS) with TIS + chemo (n=501) over PBO + chemo (n=496) as 1L treatment in patients (pts) with advanced G/GEJC.This analysis examined HRQoL outcomes of the RATIONALE-305 study at final analysis.Methods: Adults with previously untreated, unresectable, or metastatic GC/GEJC, were randomized (1:1) to TIS 200 mg or PBO IV once every 3 weeks plus investigator-choice of chemo.HRQoL was assessed using EORTC QLQ-C30 and the QLQ-STO22.A mixed model for repeated measures using PRO endpoints at clinical Cycles 4 and 6 was performed.Time to deterioration was examined.Pts treated with TIS + chemo had better HRQoL outcomes vs pts treated with PBO + chemo, particularly for GHS/QoL, physical functioning, fatigue, GC/GEJC symptoms, pain/discomfort, and upper GI symptoms These results, along with prolonging of OS and other secondary efficacy endpoints, as well as a tolerable safety profile, support the benefit of TIS + chemo as a potential 1L treatment option for GC/GEJC.Clinical trial information: NCT03777657.Research Sponsor: BeiGene.The median OS for the entire cohort was 7.2 m, 3.7 m for stage IV, 17.3 m for stage III, and 84 m for stage I. Median OS for stage II was not reached, and it was 58% at 5 years.Symptoms associated with worse or better survival are shown in table.Conclusions: Reducing delays in histopathological diagnosis from symptom onset could lead to earlier detection and curative treatments.Identifying alarm signs and appropriate patient navigation would enable earlier diagnosis and early treatment.Research Sponsor: None.The effects of pre-existing psychiatric disorders on gastric cancer survival.First Author: Josephine Soddano, Department of Medicine, Columbia University Irving Medical Center, New York, NY Background: Despite advances in available treatment, gastric cancer (GC) survival remains low (34.5% overall 5-year survival).In patients diagnosed with cancer, having a prior psychiatric disorder (PD) has been associated with worse survival outcomes compared with no prior PD.Therefore, we examined the relationship between a prior PD diagnosis and GC survival.Methods: We queried the Surveillance, Epidemiology and End Results (SEER)-Medicare database from 2000 to 2017 for patients who were 66 years of age or older with histologically confirmed GC.Patients with prior cancer history, who were diagnosed by autopsy or death certificate, or were not continuously enrolled in Medicare for at least one year prior to their GC diagnosis were excluded.Patients diagnosed with a PD at least one year prior to GC diagnosis and patients without a prior PD were defined as the exposed and unexposed groups, respectively.PDs were categorized as either mild (depression and anxiety) or severe (bipolar or psychotic disorders and schizophrenia).We performed adjusted multivariable Cox proportional hazards regression modeling to evaluate the relationship between prior PD and 5year overall and cancer-specific survival.Cancer stage, histologic grade, age at diagnosis, sex, race and ethnicity, rural/urban, comorbidity, socioeconomic status, and marital status were examined as potential confounders. Results: Out of 10,464 identified GC patients, 1,651 had a prior PD (46.3% male, mean age 77.5 years) and 8,813 did not have a prior PD (61.5% male, mean age 77.4 years).Our PD patient cohort included 1,355 mild and 296 severe PD patients.When we examined overall survival, patients with a prior PD had a greater hazard of death compared to patients without a prior PD (adjusted hazard ratio: 1.12; 95% CI: [1.05, 1.19] ). However, we found no association between having a prior PD compared with not having a prior PD on GC-specific survival (adjusted hazard ratio: 1.07; 95% CI: [0.99, 1.15]). In GC patients with a prior PD, we examined the effects of severe PD versus mild PD on survival. For overall survival, severe PD patients had a greater hazard of death compared with mild PD patients

The prevalence of PD-L1 combined positive score (CPS) $ 5 before the 1L therapy was 55% for NIVO+chemo and 27% for chemo. Baseline demographic and clinical characteristics were comparable between treatment groups in the overall cohort and the CPS subgroups.

Does routine clinical assessment of older adults with gastroesophageal cancer tell the whole story?First Author: Meghan Connors, Fox Chase Cancer Center, Philadelphia, PA Background: Geriatric Assessment (GA) can help oncologists determine fitness of their older patients (pt) for anti-cancer therapy.Our objective was to compare routine provider assessment (PA) and GA of older adults with gastroesophageal cancer (GEC).Methods: Patients $65 with any stage of GEC completed a GA.The pt's provider completed a PA and abnormalities detected by both assessments were centrally reviewed and compared.GA and PA assessed functional status, nutrition, comorbidities, psychological distress, cognition, social support, and chemotherapy toxicity risk.Validated assessment tools were used for the GA.Data collected 3 months post-enrollment included hospitalization, $ grade 3 toxicities, and treatment delays.We compared the proportions detected/not detected abnormalities by PA vs GA using McNemar's test for paired data, and we measured agreement using Kappa statistics (1=full, 0=no, -1=disagreement).Pts' demographic and clinical characteristics did not predict for the identification of GA abnormalities.GA detected 196 abnormalities and PA detected 86.Majority of pts (84%) had $ 1 unidentified abnormality by PA.Providers identified more pts with clinically significant comorbidities as compared to GA.However, the GA identified more abnormalities compared to PA in all other evaluated domains (Table).Low agreement was found between PA and GA in any of the domains.Pts scoring high on the CARG chemotherapy toxicity prediction tool (p=0.004) and pts with evidence of psychological distress (p=0.049) had more $ grade 3 toxicity.Pts with abnormalities in functional status, nutrition, psychological distress, and a high CARG score were more likely to be hospitalized during therapy.Conclusions: Clinical characteristics of older pts with GEC are not predictive of GA abnormalities.While providers were better at identifying comorbidities, the GA resulted in a comprehensive evaluation of all domains and identified significant abnormalities that affect treatment outcomes in this population.Research Sponsor: NCCN -National Comprehensive Cancer Network; NCCN/Lilly 3275101.With advances in treatment and an aging population, gastroesophageal cancer (GEC) in older adults (OA) is increasing.Geriatric assessment (GA) is recommended as part of treatment decision in patients $ 65.Unfortunately, due to the complex nature and multiorgan effects of GEC, it is often difficult for oncologists to discern whether GA abnormalities are secondary to aging or the GEC itself.Because of their objectivity, fitness trackers are becoming increasingly popular in the functional evaluation of cancer patients.While fitness trackers have shown feasibility and validity in some cancers, data for their use in OA is currently limited.Objective: Evaluate the feasibility of functional status assessment via Fitbit activity tracker (FB) in comparison to traditional geriatric assessments in OA with GEC.Methods: Patients age $65 with any stage of GEC completed a GA and were given a FB to wear for 3 days in line with the battery life of the device.GA included a comprehensive evaluation of all geriatric domains with functional status assessed by performance status (PS), falls, Timed Up and Go (TUG), Activities of Daily Living (ADLs), and Instrumental Activities of Daily Living (IADLs).FB collected total steps per day (SPD), and patients' mean SPD was calculated.We compared patient characteristics and outcomes using Fisher's exact and Wilcoxon tests grouped by below and above median SPD.Results: 82 patients completed GA, of which 69 (84%) wore FB for $8 hours.Mean SPD for all patients was 2827 (38 -11032), Conclusions: FB use for short objective evaluation functional status is feasible among OA with GEC and provides data which correlates with other GA abnormalities and treatment tolerance.Additional research is warranted to further incorporate this assessment tool into clinical care.Research Sponsor: None.Logistic regression models were used to evaluate the association of age and SMG with 90-day surgical mortality.Patients were classified based on their predicted probability of 90 day mortality into low and high risk groups, where high risk was defined as the highest-risk 25% of patients.This model was then applied to the study cohort of patients with ACA.Log-rank tests were used to compare overall survival by treatment (CRT vs CRT+S) in the high risk and low risk groups.Results: Of 316 patients with locally advanced ACA treated with CRT, 254 underwent surgery (CRT+S).90-day post operative mortality in the CRT+S group was 5.1%.74 patients were categorized as high-risk and 242 as low-risk.Patients were grouped into quartiles of SMG and by age ($75 and ,75 years).90-day postoperative mortality for the high risk group in the bottom SMG quartile (Q1) was compared to the low-risk group in the top 3 quartiles (Q234).Moving towards a personalised understanding of the nutritional impact of self-expanding metallic stents (SEMS) in gastro-oesophageal cancer: A retrospective case note review of a tertiary referral oncology centre. First Author: Aimee Cunningham, The Christie NHS Foundation Trust, Manchester, United Kingdom Background: Dysphagia is a common life-impacting complication for patients with gastro-oesophageal (O-G) cancer. Options to alleviate dysphagia include insertion of SEMS or percutaneous endoscopic gastrostomy (PEG). SEMS improve quality of life by enabling a person to eat a varied diet, but are associated with complications including pain and need for reintervention. Although studies have shown SEMS improve dysphagia, consequent longitudinal impact on nutritional status has not been evaluated. There is a need to better characterise risks and benefits of SEMS to allow a personalised approach to both insertion and follow-up. Methods: We identified patients with a confirmed diagnosis of O-G cancer, who underwent SEMS insertion at The Christie NHS Foundation Trust in 2021 and 2022. Data was retrospectively collected about patient and stent characteristics, and patient outcomes to quantify benefits and risks of SEMS. SEMS-related toxicity or stent failure within 30 days, and 20% developed significant pain within 24 hours of SEMS insertion. Conclusions: SEMS provide meaningful nutritional benefit in the majority of patients with O-G cancer, as weight loss is significantly slowed following insertion. However, we identified two groups of patients who did not benefit from SEMS; those who continued to lose weight and those who had stent failure. We did not find predictive factors for stent failure from multivariate analysis of baseline demographics or stent characteristics. Therefore, more detailed analysis of tumour factors, imaging findings and SEMS location from a larger cohort of patients may be required to identify patients who are unlikely to benefit from SEMS, and alternative interventions such as PEG feeding could be considered. Research Sponsor: None.

Pathologic complete response among patients with esophageal cancer receiving neoadjuvant chemotherapy or chemoradiation: A meta-analysis.First Author: Charles Gaber, University of Illinois-Chicago, Chicago, IL Background: Although neoadjuvant therapy improves overall survival in esophageal cancers, the benefit is largely confined to those with the greatest pathologic response.Current estimates of pathologic complete response (pCR) rates come from individual studies and lack precision.With this study, we sought to estimate summary pCR rates in patients with non-metastatic esophageal cancer who received either neoadjuvant chemotherapy or chemoradiation by conducting a systematic review and meta-analysis of clinical trials.Methods: Studies were identified from the Medline, EMBASE, and CENTRAL database searches.Eligible studies were published in English from 1992-2022 and consisted of clinical trials that focused on incident non-metastatic esophageal cancer or cancer of the gastroesophageal junction.Trials were required to contain at least one arm of patients receiving neoadjuvant chemotherapy (including perioperative) or neoadjuvant chemoradiation (including treatment with induction chemotherapy).Eligible studies had to report pCR in at least 20 patients who underwent neoadjuvant therapy and surgery.Pooled pCR prevalence was determined using the Freeman-Tukey double arcsine transformation and a random effects model.Results:Among 6,575 records first identified, we included 75 studies with 5,988 patients in the meta-analysis.NIVO + chemo demonstrated superior overall survival (OS) and clinically meaningful progression-free survival (PFS) benefit vs chemo and an acceptable safety profile in previously untreated, advanced non-HER2+ GC/GEJC/EAC, leading to approvals in many countries.NIVO + chemo continued to demonstrate clinically meaningful improvement in efficacy at 2 and 3-yr follow-ups.We present 4-yr follow-up results for NIVO + chemo vs chemo from CheckMate 649.Methods: Adults with previously untreated, unresectable advanced, or metastatic GC/GEJC/EAC were enrolled, regardless of programmed death ligand 1 (PD-L1) expression.HER2+ patients (pts) were excluded.Randomized pts received NIVO (360 mg Q3W or 240 mg Q2W) + chemo (XELOX Q3W or FOLFOX Q2W), NIVO + ipilimumab, or chemo.Dual primary endpoints for NIVO + chemo vs chemo were OS and PFS by blinded independent central review (BICR) in pts with PD-L1 combined positive score (CPS) $ 5.Results: 1581 pts were randomized to NIVO + chemo or chemo.At the 48-month (mo) minimum follow-up, NIVO + chemo continued to demonstrate OS and PFS benefit vs chemo in pts with PD-L1 CPS $ 5 and all randomized pts (Table)OS benefit with NIVO + chemo was observed in most prespecified subgroups.Objective response rates (ORR) were higher and responses were more durable with NIVO + chemo vs chemo in pts with PD-L1 CPS $ 5 and all randomized pts (Table). In the exploratory analysis of OS by response at the 18-week landmark timepoint, there were numerically more pts achieving response with NIVO + chemo vs chemo, and median OS (95% CI) with NIVO + chemo was numerically longer in responders vs non-responders both in pts with PD-L1 CPS $ 5 (20.5 [17.5-25.0] vs14.0 [11.6-15.7])andall randomized pts (19.4 [17.5-21.7]vs13.1 [11.6-14.4] ).No new safety signals were identified, consistent with the 3-yr follow-up.Conclusions: NIVO + chemo is the first PD-1 inhibitor/chemo combination to demonstrate long-term efficacy and acceptable safety after 4 yrs of follow up in previously untreated advanced GC/GEJC/EAC.These results are consistent with earlier follow-ups, further supporting NIVO + chemo as a standard 1L treatment in these pts.Clinical trial information: NCT02872116.Research Sponsor: Bristol Myers Squibb.Results: 10 pts with EC (8 adenocarcinoma, 2 squamous) and CDKN2A loss (n=5) or CDKN2A mut (n=5) were enrolled from Dec 2019 to June 2022.6pts had HER2 negative EC, 1 pt had HER2 low EC, 1 pt had HER2 positive EC, and 2 pts were not tested for HER2.All pts were evaluable for efficacy and toxicity.Table summarizes pt demographics and outcomes.1 pt with CDKN2A loss had a 27-wk PR for a DC rate of 10% (1-sided 90% CI, 1% to 100%) and OR rate of 10% (95% CI, ,1% to 45%).The null DC rate was not rejected (p=0.80).Median PFS was 8 wks (95% CI, 2 to 13) and median OS was 17 wks (95% CI, 9 to 35).The pt with PR had HER2 negative adenocarcinoma, ECOG PS of 1 and 2 prior lines of therapy.4pts had 12 serious adverse events at least possibly related to tx, including anemia, atrial fibrillation, increased creatinine, dehydration, dyspnea, generalized muscle weakness, heart failure, lung infection, pericardial effusion and thrombocytopenia.4pts had a drug-related grade 3 AEs including anemia, increased bilirubin and thrombocytopenia.Conclusions: Abemaciclib monotherapy did not demonstrate sufficient clinical activity in pts with advanced EC with CDKN2A loss or mut for continued evaluation in this pt population.Other tx should be considered for these pts, including tx offered in clinical trials.Clinical trial information: NCT02693535.Research Sponsor: Eli Lilly and Company; AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Genentech, Merck, Pfizer, Seagen, Taiho Oncology.First Author: Daisuke Takahari, Gastroenterological Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Koto City, Tokyo, Japan Background: Currently no HER2 directed therapy is available in the perioperative setting for gastric and gastroesophageal junction (GEJ) cancer.Trastuzumab deruxtecan (T-DXd) received regulatory approval based on the encouraging efficacy demonstrated in the DESTINY-Gastric01 and DESTINY-Gastric02 studies in pretreated patients (pts) with metastatic gastric and GEJ cancer.This multicenter phase 2 study aimed to evaluate the clinical activity and safety of neoadjuvant T-DXd for locally advanced gastric and GEJ cancer.Methods: Eligible pts possessed previously untreated locally advanced gastric and GEJ adenocarcinoma with clinical stage of T2-4 and/or N+ without distant metastasis.The main cohort enrolled pts exhibiting HER2-positivity, defined as IHC 3+ or IHC 2+ with ISH+ by local assessment.An exploratory cohort included patients with HER2-low expression (IHC1+ or 2+ with ISH negative) with serum HER2-ECD exceeded 11.6 ng/ml.Treatment included three cycles of T-DXd administered every 3 weeks, followed by surgery.The primary endpoint was the major pathological response (MPR) rate by central assessment, with an expected rate of 45% and a futility threshold of 20%.The planned sample size in the main cohort was 27 pts with one-sided alpha of 10% and power of 90%, while an additional 10 pts would be enrolled into the exploratory cohort.Pre-and post-treatment samples were subjected to biomarker analyses.Clinical trial identification: NCT05034887.Results: Between November 2021 and November 2022, 27 pts were enrolled into the main cohort from seven Japanese sites.The majority of the pts had IHC3+ (24pts).The primary sites were gastric (16 pts) and GEJ (11 pts).Clinical stages ranged from II/III/IVa: 2/21/4 pts.Of the cohort, 26 pts completed planned 3 courses of T-DXd and one pt discontinued because of toxicity.R0 resection was achieved in 25 pts, with one undergoing R1 resection.The MPR rate as the primary endpoint was 14.8% (80% CI 6.6 % -27.5 %) which did not surpass the predefined 20%.The efficacy and safety of conversion therapy after initial systemic chemotherapy in advanced esophageal cancer with distant metastases: A multicenter retrospective observational study. First Author: Takayuki Tsuji, Department of Surgery, Keio University School of Medicine, Shinjuku-Ku, Japan Background: Systemic chemotherapy, with or without radiation, has been the standard treatment for esophageal squamous cell carcinoma (ESCC) with distant metastasis. The increased efficacy of multimodality treatment allows for the consideration of conversion therapy with curative intent for initially unresectable ESCC after initial treatment. In the present study, we examined the safety and effectiveness of conversion therapy for ESCC. Methods: Conversion therapy was defined as surgery or chemoradiation therapy (CRT) aiming at cure after initial treatment for tumors that were initially unresectable due to distant metastasis. The patients who underwent conversion therapy for ESCC between 2011 and 2021 at participating institutions were retrospectively reviewed. Patient backgrounds, treatment outcomes, and overall survival (OS) were evaluated.

Neutrophil-to-lymphocyte ratio to predict metachronous cancer after curative resection of early gastric cancer.First Author: Sunsuk Kim, Korea University Guro Hospital Healthcare System, Seoul, South Korea Background: We investigate the predictive value of inflammatory markers for occurrence of metachronous cancers among patients who underwent endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) and are judged as curative resection (CR).Methods: We enrolled patients who were diagnosed as EGC and underwent ESD during 2006 and 2020.We retrospective collected data of inflammatory indexes such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and erythrocyte sediment ratio (ESR).Clinical outcomes of early gastric cancer resected by endoscopic submucosal dissection at young age. First Author: Jong-Jae Park, Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea Background: A small portion of patients are diagnosed as early gastric cancer (EGC) and undergo endoscopic submucosal dissection (ESD) at young age, however, their clinical outcomes are rarely known. We investigated clinical characteristics and outcomes of patients who underwent ESD for treatment of EGC at age under 50. Methods: We enrolled patients who were diagnosed as EGC and underwent ESD during 2006 and 2020. We divided them either for young age (YA) group if age # 50 years and other age (OA) group if . 50 years.

phase Ib/II study of ASKB589 (anti-Claudin 18.2 [CLDN18.2] monoclonal antibody) combined with CAPOX and PD-1 inhibitor as first-line treatment for locally advanced, relapsed and metastatic gastric/gastro-esophageal junction (G/GEJ) adenocarcinoma. First Author: Zhi Peng, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China Background: ASKB589 is a humanized IgG1 monoclonal antibody against Claudin 18.2 (CLDN18.2) with high affinity and enhanced antibody-dependent cytotoxicity. We report preliminary safety and efficacy data from an ongoing Phase Ib/II, dose-escalation and expansion study of ASKB589 combined with capecitabine, oxaliplatin(CAPOX) and Sintilimab as first-line treatment of G/GEJ adenocarcinoma (NCT05632939).

CheckMate 649 Chinese subgroup analysis 4-year (yr) follow-up.First Author: Lin Shen, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China Background: NIVO + chemo demonstrated clinically meaningful improvement in overall survival (OS) and an acceptable safety profile vs chemo in previously untreated Chinese pts from CheckMate 649, consistent with the overall study population with advanced GC/GEJC/EAC.1LNIVO+ chemo is approved for advanced GC/GEJC/EAC in multiple countries, including China.We report 4-yr results of NIVO + chemo vs chemo in Chinese pts from CheckMate 649.No new safety signals were identified (Table).Conclusions: After 4 yrs of follow-up, NIVO + chemo continued to demonstrate clinically meaningful survival benefit and more durable responses vs chemo in Chinese pts, with an acceptable safety profile.These results are consistent with previous reports and with the overall study population with advanced GC/GEJC/EAC and further support NIVO + chemo as a standard 1L treatment option for Chinese pts.Clinical trial information: NCT02872116.Research Sponsor: Bristol Myers Squibb.To assess the heterogeneity of the study outcomes, the I2 statistic was obtained.The I2 statistic represented the variability in the meta-analysis attributed to study heterogeneity.These analyses were applied to the overall cohort of studies, as well as within the liver metastasis (yes or no) sub-cohorts.All analyses were conducted in SAS v9.4 (Cary, NC) at a significance level of 0.05.Results: Seven Phase III RCTs were includedthat had available data on overall survival and/or progressive free survival in patients with liver metastasis.Of these, six were in the frontline setting and one in the later line.Overall, 6,109 patients were included.Clinicopathological characteristics and lymph node metastasis rates in early gastric lymphoepithelioma-like carcinoma: Implications for endoscopic resection. First Author: Tae-Se Kim, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea Background: We aimed to clarify the clinicopathological features and the rate of lymph node metastases (LNM) of early gastric lymphoepithelioma-like carcinoma (LELC). Methods: We compared the clinicopathological characteristics of 82 LELC and 5758 well-or moderately differentiated (WD or MD) tubular adenocarcinoma patients who received gastrectomy for single early gastric cancer (EGC). Lymphatic invasion was the only significant risk factor in the regression analysis for LNM in LELC patients. Among 12 patients with mucosal or shallow submucosal invasion and 27 patients with deep submucosal invasion having small tumor sizes (less than 2 cm) and no lymphatic invasion, there was no LNM. Conclusions: Given the low rate of LNM, the same curability criteria of ESD for WD or MD EGC may be applied to early LELC and even more flexibly for those considered non-curative ESD only because of deep submucosal invasion. Research Sponsor: None.

This open-label, single-arm, phase II study consists of dose-finding and dose-expansion phases, enrolling advanced or metastatic ESCC patients after first-line immunotherapy failure. The dose-finding phase followed a 3+3 design.

Results: 152 pts were randomized to: CT (n=24; control); atezo + CT (n=65) or tira + atezo + CT (n=63).As of 14 Mar 2023, median follow-up was 8.7 months (mo) in the CT arm, 11.4 mo in the atezo + CT arm and 10.9 mo in the tira + atezo + CT arm.Pt characteristics were generally balanced between arms.ORR was 47.8% (CT) vs 53.8% (atezo + CT) vs 67.7% (tira + atezo + CT).Median PFS was 4.1 mo (CT) vs 6.8 mo (atezo + CT) vs 6.9 mo (tira + atezo + CT) (Table).ORR and PFS benefit was generally consistent across all pre-specified subgroups, including PD-L1 status.There was a numerical improvement in OS with tira + atezo + CT vs atezo + CT and CT alone (Table).Grade 3-5 adverse events (AEs) were 82.6% vs 83.1% vs 85.5% and treatment-related Grade 4/5 AEs were 4.3% vs 7.7% vs 14.5% for CT vs atezo + CT vs tira + atezo + CT.AEs leading to any tx discontinuation were 21.7%, 16.9% and 35.5%, respectively.Conclusions: Clinically meaningful improvements in INV-assessed ORR and PFS and a trend of improved OS were observed with tira + atezo + CT when compared with CT and atezo + CT.These results support the contribution of both tira and atezo in combination with CT.The safety profile was consistent with the known risks of the individual tx.Clinical trial information: NCT03281369.Research Sponsor: F. DEP cabazitaxel was welltolerated with mostly mild (62.9%, Grade (G) 1)/moderate (20.2%, G2) treatment-related adverse events (TRAEs), including nausea, vomiting, fatigue, neuropathy, neutropenia (only 1 pt had G-CSF Tx, 1 pt had secondary G-CSF prophylaxis) and anemia, that were like those observed with standard cabazitaxel Tx. Of severe TRAEs (G3/4; 16.9%) most (80%) were observed in 2 pts, including neutropenia, anemia, thrombocytopenia, fistula, elevated liver enzymes. Conclusions: DEP cabazitaxel exhibited highly encouraging anti-tumor activity in .1L, advanced EGC in multiple anatomic locations and of different histological sub-types. The preliminary efficacy and safety results compare favorably to available treatment options and highlight the promising clinical potential of DEP cabazitaxel in advanced EGC. Clinical trial information: EudraCT 2017-003424-76. Research Sponsor: Starpharma Pty Ltd. Poster Session Pembrolizumab, radiotherapy, and chemotherapy in neoadjuvant treatment of malignant esophago-gastric diseases (PROCEED): Assessment of survival and patterns of recurrence in a prospective, phase II single-arm trial. First Author: Pooja Karukonda, Duke Cancer Institute, Durham, NC Background: Locally advanced esophagogastric adenocarcinoma (EGA) is commonly treated with neoadjuvant chemoradiation (CRT) prior to surgical resection. Adjuvant immunotherapy has been shown to improve outcomes for these patients. The primary objective of this trial was to investigate whether neoadjuvant pembrolizumab (P) + CRT improves pathologic complete response (pCR) compared to historical control of neoadjuvant CRT alone. Exploratory endpoints included time to local recurrence (TTLR), time to distant recurrence (TTDR), progression-free survival (PFS), and overall survival (OS). Methods: Single-institution, prospective phase II trial (NCT03064490) evaluating neoadjuvant P + CRT followed by adjuvant P in patients with locally advanced operable EGA. CRT (45 Gy in 25 fractions with concurrent, weekly carboplatin [AUC 2] and paclitaxel [50mg/ m2 of BSA] ) with three cycles of P were administered as neoadjuvant therapy. Patients also received three cycles of adjuvant P. Pathologic response was scored from 0-3 based on tumor regression grading (TRG): 0 indicating a complete response, 1 marked response (,10% residual disease), 2 partial response, and 3 poor or no response. pCR was defined as the absence of viable tumor cells at the primary tumor site and all resected lymph nodes in the surgical specimens (ypT0N0, TRG 0). Major pathologic response (MPR) was defined as TRG 0-1. Treatment-responders (R) are those with MPR, while non-responders (NR) are those with TRG 2-3 TTLR was time from enrollment to local recurrence (LR); distant recurrences (DR) were ignored and deaths were censored. TTDR was defined analogously. PFS was time from enrollment to LR, DR, or death due to any cause. OS was time from enrollment to death due to any cause. The Kaplan-Meier method was used to estimate TTLR, TTDR, PFS, and OS. Two-sided statistical tests were performed with an a of ,0.05 considered significant. Results: 35 patients were enrolled from 2017-2022. 30 underwent neoadjuvant P + CRT followed by surgical resection. pCR and MPR rates were previously reported: 35.5% and 50%, respectively. Median follow-up of the whole cohort was 35.5 mo. PFS was significantly improved in R vs NR (p=0.046), and there was a trend towards improved OS (p=0.084), and TTDR (p=0.069). There was no significant difference in TTLR (p=0.128). At three years, in R vs NR, PFS was 72.7% vs 46.2%, OS was 80.0% vs 58.3%, TTLR was 100% vs 81.8%, and TTDR was 81.8% vs 53.8%. Conclusions: Patients undergoing neoadjuvant P + CRT for EGA experienced higher rates of pCR/MPR compared to historical controls treated with CRT alone. MPR correlated with improved PFS, with a trend towards improved OS, indicating the clinical significance of pathologic response. These correlations appear to be driven primarily by decreased risk of developing distant metastases. Clinical trial information: NCT03064490. Research Sponsor: Merck.

The role of exosomal LINC00853 in gastric cancer progression.First Author: Sang Kil Lee, Yonsei University College of Medicine, Seoul, South Korea Background: Examination of various substances contained in exosomes (EXOs) as biomarkers is being actively conducted.Long non-coding RNAs (lncRNAs) are garnering interest in the diagnosis of gastric cancer.In this experiment, we attempted to obtain lncRNAs that drive the onset and recurrence of gastric cancer and elucidate the mechanism to observe their potential as exosomal biomarkers.Methods: LncRNA expression profiling was conducted using ArrayStar Human LncRNA array 2.0 for the patient's tissues who underwent endoscopic resection that reflected early gastric cancer onset and recurrence.The proliferation, apoptosis, invasion, and migration of AGS and MKN74 cells were measured after treatment with pcDNA over expressing vector and two different siRNAs.To observe the interaction between lncRNA and MAP17, RNA immunoprecipitation (IP) and electrophoretic mobility shift assay were conducted.EXOs were extracted from patient samples and gastric cancer cell lines, which were then administered to gastric cancer cells.Results: Five target lncRNAs (LINC00853, LINC00634, LINC01535, GAPLINC, and AC017002.1)were selected by performing a lncRNA microarray analysis.The validation results showed that LINC00853 was upregulated in gastric cancer tissues compared to that in paired adjacent non-cancer tissues.LINC00853 induced proliferation and suppressed apoptotic signaling of AGS and MKN74 cells.LINC00853 promoted the invasion and migration of AGS and MKN74 cells.LINC00853 bound with its neighbor gene MAP-17 and activated it via the downstream PDZK1/AKT signaling pathway.LINC00853 and MAP-17 cooperatively acted as oncogenes in gastric cancer.EXOs derived from patients with gastric cancer and those from gastric cancer cell lines (AGS, MKN74) contained LINC00853.Knockdown of LINC00853 decreased LINC00853 expression in EXOs, which, in turn, reduced the oncogenicity of LINC00853 exosome in AGS cells.Cellular and exosomal LINC00853 exert an oncogenic effect via MAP-17-related cell signaling in gastric cancer.Conclusions: Exosomal LINC00853 can be a candidate biomarker of occurrence of recurrence of gastric cancer.Research Sponsor: None.Genomic analysis of oesophageal carcinoma (EC) to identify recurrent mutations in histone methyltransferases as a distinctive subset. First Author: Jingyuan Wang, Department of Medical Oncology, Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China Background: Histone-lysine N-methyltransferase 2 (KMT2) family proteins methylate lysine 4 on the histone H3 tail at important regulatory regions in the genome and thereby impart crucial functions through modulating chromatin structures and DNA accessibility, which is associated with tumorigenesis and immune tolerance, indicating its possible correlation with the efficacy of immunotherapy. Recurrent mutations of KMT2 have been identified in EC, but data addressing the molecular features of KMT2 mutated (MT) EC are lacking. We aimed to understand the molecular profile of KMT2 -MT EC. Fragment analysis and NGS. Results: The mutation spectrum of KMT2A/C/D was significantly different between ESCC and EAC ( KMT2A, 2.7% vs. 1.2%; KMT2C, 3.8% vs. 1.2%; KMT2D, 14.2% vs. 2.0%, P ,0.05). KMT2-MT EAC tumors showed significantly higher mutation rates in CIC (13% vs 1.1%), NF1 (12.5% vs 2.2%), FBXW7 (12% vs 3.4%), ATM (11.5% vs 2.6%) and BRCA1 (11.5% vs 1%, all q,0.05), compared to KMT2-WT tumors. However, in ESCC there were no significant differences in gene mutations between the KMT2-MT and WT groups. Significantly higher rates of dMMR/MSI-H (19.2% vs 1.0% in EAC, 5.4% vs. 0% in ESCC, both p,0.01) were seen in both KMT2-MT ESCC and EAC, compared to KMT2-WT cohorts, respectively. TMB was significantly higher in both KMT2-MT ESCC (median: 10 vs 8.6 mut/Mb, P=0.042) and EAC (23.9 vs 8.0 mut/Mb, P,0.0001), compared to KMT2-WT cohorts, respectively. A numerically longer immune-related overall survival was observed in KMT2 -MT EC patients, compared to KMT2 -WT EC patients (9.05 vs 6.98 months, HR=0.744, 95%CI: 0.52-1.07, P =0.11). Conclusions: This is the largest study to investigate the distinct genomic landscapes between KMT2 -MT and WT EC to date. Our data showed the KMT2 -MT EC has a distinctive genetic profile, indicated by higher TMB, and higher frequency of dMMR/MSI-H and gene mutations involved in DDR and epigenetic regulation. Understanding these molecular characteristics may be informative in the development of effective treatment strategies in KMT2 -MT EC. Research Sponsor: None. Combining PARP inhibitor and irinotecan is known to synergize cytotoxicity. The aim of this analysis was to evaluate the association of HRD and efficacy of irinotecan and venadaparib combined, in patients with metastatic GC who had failed at least 2 lines of therapy. Methods: MTT assays were performed in vitro to verify and characterize synergism between venadaparib and SN-38. Data were analyzed using the GraphPad Prism (version 9.5.1) and CompuSyn (version 1.0) software. Patients with at least two prior palliative treatments were enrolled in a multinational phase Ib trial (NCT04725994). Tumor response was evaluated according to RECIST 1.1. Exploratory genomic analysis was included to assess the correlation between efficacy and HRD. Genomic analysis was conducted using ctDNA (GuardantOMNI Gene Panel version 1.0, Redwood City, CA) on Day 1 pre-dose. Results: In MTT assays, the combination of SN-Gastric microbiota, including H. pylori, may play a role in the development of gastric cancer. This study aimed to investigate the gastric microbiota throughout the stages of gastric carcinogenesis, encompassing atrophic gastritis, gastric dysplasia, and gastric adenocarcinoma. Methods: From December 2021 to August 2023, we collected gastric mucosal tissue samples from patients with atrophic gastritis, gastric dysplasia, and early gastric cancer. Subsequently, we conducted 16S rRNA gene profiling through next-generation sequencing. We compared alpha-diversity and beta-diversity within each group and analyzed the taxonomic composition. Results: This study included a total of 98 patients, comprising 16 with atrophic gastritis, 23 with low-grade dysplasia, 15 with high-grade dysplasia, and 44 with early gastric cancer. The H. pylori infection status was comparable across all groups. While there was a difference in alpha diversity between tumor lesions and normal stomach lesions, it did not reach statistical significance. Notably, Phyllobacterium was dominant in early gastric cancer, Prevotella in high-grade dysplasia, and Kocura in low-grade dysplasia. Furthermore, within the early gastric cancer group, Bacillus was widely distributed in cases of undifferentiated type adenocarcinoma. Conclusions: The analysis of microbiota collected from Korean stomach tissue revealed distinct microbial distributions across the various stages of gastric carcinogenesis. Research Sponsor: None. Detection of early-stage gastrointestinal cancers by micronuclei DNA from erythrocytes. First Author: Haobo Sun, School of Life Sciences, Westlake University; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, China Background: Gastrointestinal (GI) cancers account for over a third of cancer deaths. However, their early detection remains a challenge. Micronuclei (MN) are extranuclear bodies containing damaged chromosome segments indicative of genomic instability. Increased MN frequency in hematopoietic cells is observed in patients with solid tumors. Unlike cell-free DNA, mnDNA are chromosomal fragments in the cytoplasm. The abundance of erythrocytes in peripheral blood provides an easily accessible source for mnDNA enrichment. This pilot study illustrates the potential of mnDNA as a tool for early GI cancer detection, contributing to large-scale efforts towards developing an effective GI cancer screening test. Research Sponsor: Timing Biotech. Esophageal adenocarcinoma (EAC) is a deadly cancer with a low survival rate and limited treatment options. Receptor tyrosine kinase inhibitor, sitravatinib, selectively targets tumor associated macrophage (TAM) family receptors, AXL, TYRO3 and MERTK, and split family receptors, VEGFR, PDGFR, KIT and MET. In solid tumors, sitravatinib has been shown to potentiate PD-1 blockade by production of pro-inflammatory cytokines and reducing MDSCs, Tregs and TAMs, in the tumor microenvironment (TME).

Relationship between the number of positive MSI markers and the efficacy of NIVO+IPI therapy in MSI-H gastric cancer: A subgroup analysis of NO LIMIT study (WJOG13320G/CA209-7W7). First Author: Kenro Hirata, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan Background: Although high instability of microsatellite lesion (MSI-H) is an established biomarker for response to immune checkpoint inhibitors, the relationship between the number of MSI markers and the efficacy of immune checkpoint inhibitors in MSI-H tumors has not been well elucidated. There was no difference in PFS or OS between the two groups. Conclusions: The number of MSI markers is not related to the efficacy of NIVO+IPI in NO LIMIT study. Further follow-up is needed to confirm the relationship between survival. 1. Muro K, et al. ESMO Congress 2023. Clinical trial information: jRCT2080225304. Research Sponsor: Bristol Myers Squibb. First Author: Sun Mi Lee, Indiana University School of Medicine, Indianapolis, IN Background: The frequency of microsatellite instability-high (MSI-H) phenotype in sporadic gastric cancers (GCs) widely varies from 8% to 20%. From prior data, MSI-H phenotypes are significantly associated with female sex, older age, antral location of the tumor, well to moderate differentiation, intestinal type, non-signet ring cell component, mucinous histologic type, a moderate to severe lymphoid stromal reaction, and a lower TNM stage. This study investigated the proportion and distribution of PD-L1 expression of MSI-H GCs compared to microsatellite stable (MSS) GCs.

Molecular profiling of hepatoid adenocarcinoma and adenocarcinoma with enteroblastic differentiation.First Author: Yosuke Matsumoto, Division of Gastric Surgery, Shizuoka Cancer Center, Nagaizumi, Japan Background: Hepatoid adenocarcinoma (HAD) and adenocarcinoma with enteroblastic differentiation (ACED) are rare types of gastric cancer that produce alpha-fetoprotein (AFP) and morphologically resemble liver or fetal gut cells.The molecular characteristics of these tumors are poorly understood.We aimed to investigate the molecular profile of HAD and ACED in the comparison with common type of gastric cancer.Role of heat shock protein 90 in hypoxia-induced angiogenesis and epithelial-mesenchymal transition for esophageal squamous cancer cells. First Author: Ching Tzao, Cardinal Tien Hospital, New Taipei City, Taiwan Background: Hypoxia is known as an important trigger for the development and progression of human cancers. Heat shock proteins (Hsps) may be up-regulated in response to cellular stressors including hypoxia. To date, the functional role of Hsps within hypoxic tumor microenvironment for esophageal squamous cell cancer (ESCC) remains poorly defined. Methods: CoCl2 was used to induce hypoxia that mimics a hypoxic tumor microenvironment in cultured ESCC cells. Our data have shown that CoCl2 induced hypoxia promotes EMT and angiogenesis, which are inhibited by 17-DMAG, suggesting that hypoxia induced EMT and angiogenesis is Hsp 90 dependent in ESCC. Research Sponsor: Ministry of Science and Technology, Republic of China.

First Author: Hokyoung Lee, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea Background: It is well-established that the gastric microbiota undergoes significant alterations during the process of gastric carcinogenesis.This study aimed to identify gastric mucosa-associated microbiome (MAM) for the prediction of metachronous recurrence after endoscopic resection of gastric neoplasms.Methods: Subgroup analyses were conducted for 81 patients (early gastric cancer: dysplasia = 55:26) from a prospective cohort(Clinical Trials No. NCT04830618). Demographic data, and history of Helicobacter pylori eradication therapy, endoscopic and histologic findings were incorporated. The profile of Gastric MAM obtained from non-cancerous corporal biopsy specimens and was analyzed by 16S rDNA sequencing. Results: Over a median followup duration of 53.8 months, 16 metachronous gastric neoplasms (10 adenomas and 6 adenocarcinomas) developed. Baseline gastric MAM varied with H. pylori infection status, but was unaffected by the presence of atrophic gastritis, intestinal metaplasia or synchronous lesions. The group with metachronous recurrence did not exhibit distinct phylogenetic diversity compared with the group devoid of recurrence. b-diversity analysis showed significant difference between the two groups (weighted UniFrac distance, PERMANOVA p = 0.006). In the LEfSe analysis, metachronous recurrence group had an increased abundance of Corynebaceriaceae, Comamonadaceae, Corynebacterium, Curvibacter, and a decreased abundance of Helicobacteraceae, and Helicobacter. The total study population were classified into two distinct gastrotypes by baseline Gastric MAM (gastrotype 1: Helicobacter-dominant, gastrotype 2: Akkermansia-abundant). MAM of gastrotype 1 had higher abundance of Helicobacter pylori, and lower abundance of Akkermansia¸Comamodaceae, Muribaculacae, Streptococcus, Corynebacteriaceae, Cutibaterium. Patients in gastrotype 2 showed higher risk of metachronous recurrence than gastrotype 1 (hazard ratio = 4.621 by Cox proportional hazard model, p-value = 0.0185). Conclusions: Gastric cancer patients can be classified into two distinct gastrotypes by their MAM profiles, which were associated with different risk of metachronous recurrence. MAM profiling of gastric cancer patients is expected give insight into their risk of metachronous recurrence. Clinical trial information: NCT04830618. Research Sponsor: None.

Expression of claudin 18.2 in peritoneal metastasis (PM) of gastric cancer.First Author: Akira Saito, Jichi Medical University, Shimotsuke, Japan Background: Prognosis of patients with gastric cancer (GC) with peritoneal metastasis (PM) still remains poor, and new treatment strategies are needed.Claudins (CLDNs) are main components of tight junctions that physiologically mediate cell-cell adhesion and regulate selective permeability in epithelial cellular sheets.Recent clinical trials have demonstrated that monoclonal antibodies (mAb) to CLDN18.2 have been shown to improve the outcome of the patients with unresectable metastatic GC, especially with undifferentiated histology.However, the clinical effects of the anti-CLDN18.2mAb for patients with PM is unclear.In this study, we evaluated the expression of CLDN18.Association of methylation silencing of ULK2 via epithelial-mesenchymal transition and differentiated gastric cancers. First Author: Iori Motoo, Third Department of Internal Medicine, University of Toyama, Toyama, Japan Background: Diffuse-type gastric cancers (DGC) typically have a poor prognosis related to their invasion and metastasis, in which the epithelial-mesenchymal transition (EMT) is the initiation step. ULK2 plays a role in the autophagy initiation, which might provide a survival advantage in cancer cells. Although knock-down of ULK2 reportedly induces autophagy and EMT in a lung cancer cell line, the mechanism of EMT via the downregulation of ULK2, as well as its clinical significance, remains yet unclear. The present study, therefore, aims at clarifying this mechanism and its clinical significance in gastric cancers. Methods: We examined ULK2 mRNA expression in gastric cancer tissues and normal gastric tissues of healthy people. The effects of knock-downed ULK2 were examined in two gastric cancer cells, which were investigated in terms of their gene expression changes by the mRNA microarray. Furthermore, to investigate the carcinogenic process from normal gastric epithelial cells, we used RGE cells, which were conditionally immortalized normal gastric epithelial cells developed from a transgenic rat. Results: ULK2 mRNA expression of gastric cancer tissues was significantly lower than H. pylori-negative normal tissues. ULK2 was strongly expressed in normal tissues and intestinal-type gastric cancers (IGC) but was scarcely expressed in DGC by immunohistochemical staining. Furthermore, we found that the ULK2 methylation level of gastric cancer tissues was higher than H. pylori-negative normal tissues and IGC. Then, we validated whether knock-down of ULK2 could induce autophagy, cell migration, and EMT in NUGC3 and MKN45 cells. Using mRNA microarray analysis, we confirmed that knock-down of ULK2 changed expressions of oncogenic genes associated with cell migration and EMT. Autophagy inhibitor suppressed cell migration and EMT induced by knock-down of ULK2 in NUGC3 and MKN45. Additionally, we found that knock-down of Ulk2 induced apoptosis in normal gastric epithelial cells. Conclusions: Methylation silencing of ULK2 in gastric cancer cells could induce cell migration and EMT by means of autophagy induction, causing transformation to poorly differentiated cancers. Research Sponsor: None.

ICI + chemotherapy (chemo-ICI) is becoming an increasingly common 1 st line regimen for patients with aGEJ. However, direct outcome comparison between biomarkerenriched groups receiving chemo-ICI vs. ICI monotherapy (mono-ICI) is limited in phase III trials. We sought to evaluate if TMB might identify patients for whom mono-ICI vs. chemo-ICI might be de-risked. We prospectively hypothesized that (1) patients with TMB ,10 mut/ Impact of DNA mismatch repair status on prognosis of patients with locally advanced gastric cancer in a Mexican population. First Author: Maria del Consuelo Diaz Romero, Instituto Nacional de Cancerología, Mexico City, Mexico Background: Gastric cancer (GC) is among the five most frequent and mortal cancers in the world. In Mexico, GC is the second cause of death from cancer in men between 30 and 59 years old. The role of deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) in locally advanced gastric cancer (LAGC) is still controversial. We aimed to evaluate the overall survival (OS) of patients with LAGC, according to MMR status and treatment.

Conclusions: CRPmax, which reflects the magnitude of systemic inflammation induced by surgical stress and postoperative complications in the early phase after surgery, may be a promising prognostic indicator in patients with stage II/III gastric cancer who undergo curative resection.Research Sponsor: None.Genomic profile and clinical feature of esophageal squamous cell carcinoma, focusing on MSI, TMB, and HRD status: Analysis with the national database of Japan. First Author: Ryuichi Morita, Gastoenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan Background: In Japan, cancer genome profiling (CGP) testing has been widely used from 2019, and genomic and clinical information integrated into national database (C-CAT database) is now available for secondary use for innovative research. In esophageal squamous cell carcinoma (ESCC), more than 500 patients (as of December 2022) have already undergone CGP testing. MSI-H and TMB-H ESCC are rare, and information is lacking. Using C-CAT data base, we analyzed the clinical and genomic characteristics of ESCC, especially focusing on MSI, TMB, and HRD status.

The CLAEG study (ChiCTR1900026131) is a prospective, real-world data evaluation of the clinical outcomes of patients with AEG following radical resection to investigate lymph node (LN) metastasis patterns and refine treatment strategies.

Treatment will continue for up to 2 years (for pembrolizumab) or until PD or discontinuation criteria are met. Approximately 30 patients will be enrolled in cohort F and in We are conducting the Zhen Jing trial in five Chinese centers to investigate the tolerability and efficacy of a dose-sense regimen of docetaxel, oxaliplatin and fluorouracil in MBO from GC. Cohort A is for pts in first-line setting. Cohort B is for second-line setting. Cohort C is for pts who have failed to two or more regimens. Eligible pts will receive the same experimental regimen every 28 days: docetaxel

To the best of our knowledge, this is the first Phase III clinical trial exploring the combination of anti-HER2 ADC with trastuzumab and chemotherapy in first-line GC/GEJ.This trial began in August 2023 and has enrolled 4 patients at the time of submission.Clinical trial information: NCT05980481.Research Sponsor: None.Phase II clinical study evaluating the efficacy and safety of disitamab vedotin combined with sintilimab and S-1 in the conversion treatment of HER2-overexpression unresectable gastric cancer. First Author: Han Liang, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China Background: Gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEJA) is the fifth commonest cancer and the fourth leading cause of cancer deaths worldwide. In about 30% to 40% of patients with advanced gastric cancer have lost the opportunity for radical surgery at the first diagnosis, and the overall 5-year survival rate is less than 50%. In recent years, conversion therapy has shown great promise.

S50Gy). 8 weeks after last treatment, pts will undergo tumor assessment by esophagogastroduodenoscopy with biopsies, endoscopic ultrasonography, and CT-or MRI-scans. Surgical resection would be offered only to pts in whom a locoregional persistence is confirmed. Pts with complete remission will enter the maintenance phase and will receive durvalumab monotherapy (1500 mg, Q4W) for a maximum of 12 cycles accompanied by regular tumor re-evaluation. Primary endpoint is the rate of cCR/pCR at time of re-evaluation. Secondary endpoints include rate of cCR/pCR at 1, 2 and 3 years, rate of salvage surgery, 90 day and 1 year mortality after start of treatment, safety and EMERALD-1: A phase 3, randomized, placebo-controlled study of transarterial chemoembolization combined with durvalumab with or without bevacizumab in participants with unresectable hepatocellular carcinoma eligible for embolization. First Author: Riccardo Lencioni, Department of Diagnostic and Interventional Radiology, University of Pisa School of Medicine, Pisa, Italy

factors of gallbladder cancer (GBC) in patients diagnosed over a period of 20 years: A Canadian province experience. First Author: Nima Hamidi Toussi, University of Saskatchewan, Saskatoon, SK, Canada Background: GBC is an uncommon but often fatal gastrointestinal cancer. The poor prognosis of GBC may in part be due to lack of effective screening tools and a delay in diagnosis that leads to presentation in the latter stages of the disease. The current study aims to determine outcomes of patients with GBC in relation to contextual, demographic and clinical factors in a Canadian province over a span of 20 years. Methods: In this population-based retrospective cohort study patients with GBC diagnosed in Sas-

Addressing these disparities is crucial for promoting equitable health outcomes in liver and bile duct cancer.Research Sponsor: Robert A. Winn Career Development Award; NCI-Intramural.Disparities in surgical outcomes and survival based on insurance status among patients with fibrolamellar hepatocellular carcinoma: A national perspective. First Author: Alec Czaplicki, Creighton University School of Medicine, Omaha, NE Background: Fibrolamellar hepatocellular carcinoma (FL-HCC), encompassing 1%-5% of all liver cancers, is a rare, malignant cancer that typically affects patients less than 40 years old. FL-HCC usually affects individuals with healthy livers and initially presents asymptomatically. Prior studies describe the importance of surgery on survival, with a 5year survival of about 44%-68% with surgery versus 2%-17% without surgery. Disparities in outcomes regarding surgical factors and survival between private insurance, Medicare, Medicaid, and no insurance remain unknown. This study aims to determine differential surgical factors and survival of patients with FL-HCC based on insurance status. Current guidelines emphasize the use of CT or MRI for hepatocellular carcinoma (HCC) diagnosis, with strict regulation of biopsies. However, Hepatocellular-Cholangiocarcinoma (cHCC-CC), a liver cancer variant displaying histological elements of both HCC and cholangiocellular carcinoma (CCC), typically exhibits radiological features of both HCC and CCC on imaging studies. Additionally, platinum drugs represent the most promising initial treatment option for patients with unresectable or advanced cHCC-CC, deviating significantly from the treatment approach for HCC. feature assessment among AIEs for HCC and CCC when compared to cHCC-CC. Notably, no significant differences were observed in the impact of a cirrhotic background on the diagnosis of HCC and cHCC-CC among AIEs. Furthermore, there was no significant intercontinental variability in overall liver cancer diagnosis and the diagnosis rates of the three types of liver cancer by AIEs.

Pemigatinib demonstrated efficacy in fibroblast growth factor receptor (FGFR)-altered CCA in the FIGHT-202 trial; however, limited RW evidence exists on treatment patterns and outcomes in patients (pts) with CCA treated with pemigatinib. This study assessed characteristics, FGFR2 testing patterns, treatment patterns, and outcomes of pts treated with pemigatinib for locally advanced or metastatic CCA in the United States as part of routine clinical care. Atezolizumab plus bevacizumab (A+B) is approved by the Food and Drug Administration (FDA) for treatment of advanced stage hepatocellular carcinoma (HCC) as first line systemic therapy following results of the IMBRAVE150 trial. Since its approval, limited real-world data is available. The benefit of this treatment in patients with advanced cirrhosis is still unclear, especially in patients with Child Pugh (CP) B Efficacy profile of A+B appears to be sustained in the real world. While the efficacy is inferior in CP B liver disease, A+B remains a viable option for these patients with limited treatment options and acceptable tolerability. Our study adds to the body of evidence for real world data with A+B. Research Sponsor: None.

Real-world survival outcomes and treatment patterns in patients (pts) with unresectable hepatocellular carcinoma (uHCC): Results from the OREIOS study. First Author: Stephen Chan, Department of Clinical Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China Background: Recent advances in systemic therapies have revolutionized the management of HCC. However, there is limited real-world data on treatment patterns and survival outcomes in pts with uHCC. OREIOS (NCT05239507) study determined the clinical characteristics, management patterns and survival outcomes in pts with uHCC from 12 countries across Asia, Latin America, and Middle East and Africa. Methods: This noninterventional, retrospective study included pts with Barcelona Clinic Liver Cancer (BCLC) stage B or C unresectable or advanced/metastatic HCC at index date (date of diagnosis), diagnosed between January 2017 and December 2019. We present the clinicodemographic characteristics, treatment patterns, median overall survival (mOS), landmark survival (12 and 24 months), and median progression-free survival (mPFS). Our study provides real-world data on treatment patterns and reports poor prognosis with pts reaching a mOS of ~13 months. With novel agents and combination therapies being approved for uHCC, integrating them in routine care is important to improve survival. Alongside, further real-world studies are warranted for evaluating the change in treatment patterns and prognosis. Clinical trial information: NCT05239507. Research Sponsor: AstraZeneca International.

. RFS was defined as time from curative intent therapy, by local ablation or surgical resection, until death or disease recurrence (first of: new HCC treatment, liver transplant, metastatic disease).OS was defined as time from curative intent therapy until death.Kaplan-Meier analyses were used, censoring on end of Medicare Parts A/B/D continuous eligibility or end of data availability.RFS/OS were summarized overall and by type of prior local therapy and risk of recurrence.Pts with a solitary tumor with histologic grade 3 or 4, solitary tumor .3cm,ormultipletumors were classified as high to very high risk.Pts with a solitary tumor not histologic grade 3 or 4 or a solitary tumor #3 cm were classified as low to intermediate risk.Correlation between RFS and OS was assessed using the Kendall's t rank correlation.Results: 611 HCC pts met the inclusion criteria (mean follow-up 3.3 years; mean age 73.3 years).Average (median) primary tumor size at diagnosis was 4.8 (4) cm.91.6% of pts had a solitary tumor at diagnosis.66.1% of pts experienced death or recurrence (Table).Analysis of patients (pts) with unresectable hepatocellular carcinoma (uHCC) and Child-Pugh (CP)-B liver function treated with regorafenib in routine clinical practice in the observational REFINE study. First Author: Yoon Jun Kim, Seoul National University Hospital, Seoul, South Korea Background: Pts with HCC and compromised liver function are typically excluded from clinical trials.

In REFINE, pts with uHCC and CP-B liver function had similar rates of grade 3-4 TEAEs, but a higher occurrence of serious TEAEs due to underlying cirrhosis led to more frequent permanent discontinuations in CP-B pts.Median OS in CP-B7 pts was comparable with OS in CP-B pts overall.The evaluation of prognostic models to identify CP-B pt subgroups who may benefit from regorafenib treatment is a subject for further research.1.Kim YJ, ILCA 2022.Research Sponsor: Bayer.First-line therapies in a Latino-rich cohort of US patients (pts) with hepatocellular carcinoma (HCC) and Child Pugh B (CPB) cirrhosis.First Author: Moses Andrew Alfaro, Long School of Medicine, University of Texas Health-San Antonio, San Antonio, TX Background: There are limited prospective clinical trials in patients with both HCC and CPB cirrhosis.As the prevalence of HCC and cirrhosis has been rising among Latinos in South Texas, it is crucial to examine the liver dysfunction within this demographic to understand the contributing factors to treatment patterns.Therefore, we conducted a retrospective analysis of 36 patients with both HCC and Child Pugh B (CPB) cirrhosis.Methods: A dataset of 65 patients with HCC and cirrhosis from 2009 -2019 was used to identify 36 patients with CPB treated at a Latino-Rich NCI-designated Cancer Center.We further segmented patients of Child Pugh Class B by ALBI grades (1-3) to explore variations in demographics, liver dysfunction, and first-line therapies.Results: Median age overall of the cohort is 59 (50-71).Lenvatinib and Nivolumab were given only in ALBI II (Table).Conclusions: Sorafenib was more often given to patients with CPB cirrhosis, in the first line setting; however, more patients were treated with nivolumab or lenvatinib with ALBI II.Further investigation of survival based on ALBI levels and the trajectory of liver function over time in response to different treatment approaches is underway in a larger cohort who has received newer immunotherapy-based regimens.With more agents approved for HCC, prospective clinical trials are needed in CPB and HCC.Research Sponsor: None.This retrospective observational cohort study used linked electronic health records and medical and pharmacy claims data from the Optum Market Clarity Database.Adults diagnosed with de novo or recurrent aBTC, who initiated 1L Gem-based CT between January 2016 and March 2022, were identified and followed from the index date (defined as the first administration of Gem-based CT on or after initial BTC diagnosis date) until death, end of continuous enrollment, or end of study period, whichever occurred first.Variables including patient demographics, clinical characteristics, and treatment patterns were described.Results:A total of 580 patients were included in the analysis with either de Patient-reported outcomes (PROs) < 65 or ‡ 65 years old (yo) from CARES-310 camrelizumab + rivoceranib vs sorafenib as first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC).First Author: Stephen Lam Chan, State Key Laboratory of Translational Oncology, Department of Clinical Oncology, Hong Kong Cancer Institute, The Chinese University of Hong Kong, Hong Kong, China Background: CARES-310 (NCT03764293) evaluated the combination of the anti-PD-1 inhibitor, camrelizumab (cam), and the VEGFR-2 tyrosine kinase inhibitor, rivoceranib (rivo), compared to sorafenib (sor) for the treatment of uHCC.Cam + rivo significantly improved OS and PFS compared to sor (OS, 22.1 months [mo] [95% CI 19.1-27.2] vs15.2mo [13.0-18.5]HR0.62[95% CI 0.49-0.80];one-PatientscompletedEORTC QLQ-C30 and EORTC QLQ-HCC18 at baseline, each visit, and post-last-dose follow-up periods.Endpoints included time to deterioration (TTD) with a $10-point decrease from baseline of patient reported QoL, physical functioning, role functioning, and patientreported symptoms.Results: Mean completion rates across questionnaires were 98.56% and 96.78% for cam + rivo and 98.91% and 98.75% for sor in the ,65 and $65 yo groups, respectively, from baseline through $121 weeks of treatment.In the ,65 yo group, cam + rivo vs sor had improved TTD in fatigue measured by EROTC-QLQ-C30.In the $65 yo group, cam + rivo had significantly longer median TTD of pain measured by EROTC-QLQ-HCC18 and QLQ-C30, respectively.The median TTD of appetite loss in the $65 yo group favored cam + rivo.Median TTD for jaundice was significant for sor in both ,65 yo and $65 yo group.Median GHS/HRQoL in the $65 yo group favored cam + rivo.Conclusions: Cam + rivo was associated with improvement in varied QoL aspects in both patient groups.These PRO results support the clinical benefit and use of cam + rivo in patients with uHCC who have not received prior systemic therapy. Clinical trial information: NCT03764293.Research Sponsor: Elevar Therapeutics; Jiangsu Hengrui Pharmaceuticals.Prognostic value of the timing of immune checkpoint inhibitors infusion in patients with advanced hepatocellular carcinoma.First Author: Alina Pascale, Hepato-Biliary Center, Paul Brousse Hospital, APHP, Villejuif, France Background: Experimental and clinical data in melanoma and lung cancer suggest that the response to immune checkpoint inhibitors (ICI) may be influenced by circadian rhythms.However, similar findings are lacking in hepatocellular carcinoma (HCC).The aim of this study was to assess the impact of infusion timing of atezolizumab, an ICI, associated or not with bevacizumab, as first line systemic treatment in advanced HCC.Methods: We retrospectively analyzed all consecutive patients, who received, as first line systemic treatment, at least two cycles of atezolizumab +/-bevacizumab for advanced HCC in Paul Brousse Hospital, Villejuif, France, between January 2020 and October 2022.We split them in two groups: 1) patients receiving the first two cycles after 1 pm (afternoon group); 2) patients receiving at least one of the two first cycles before 1 pm (morning or mixed group).Cox regression models were used to assess the prognostic value of ICI infusion timing for the overall survival (OS).included in the first group and were compared to 90 patients included in the second group.There were no significant clinical differences between the two groups.The median OS was significantly lower in the afternoon group compared to the morning or mixed group (11.5 months vs 18.7 months, p = 0.015).In univariate analysis, PS $ 1 (p = 0.025), initial level of alpha-fetoprotein (p = 0.030), monotherapy by atezolizumab (p = 0.004) and the first two cycles of ICI infusion after 1 pm (p = 0.018) were significantly correlated with OS.The first two cycles of ICI infusion after 1 pm remains an independent factor significantly associated with OS in the multivariate Cox model, with HR 2.29, 95% CI: 1.27-4.14,p= 0.005 (Table). Conclusions: Our results suggest that the afternoon infusion of the first two cycles of ICI is associated with lower outcomes in patients with advanced HCC, independently of other prognostic factors. There may be confounding factors due to the variability of administration of further perfusions. Larger data are needed to confirm such findings. Research Sponsor: None.

Conclusions:The diverse population in this RWS is reflective of the heterogeneous CCA pt population in the US. These realworld overall response rates support the clinical benefit of pemi across racial and ethnic groups and complement the results of the clinical trial. Research Sponsor: Incyte Corporation.

(HR 2.6[95% CI 1.03 -6.56]; p=0.04) after adjustment for aforementioned confounders.Conclusions: Frailty status assessed by patient-reported GA using CARE-FI is associated with an increased risk of mortality in older adults with HCC.Frailty assessment should be encouraged and considered in prospective clinical trials to estimate the impact of treatment on the most vulnerable adults.Research Sponsor: None.Has management of locally advanced intrahepatic cholangiocarcinoma evolved with the evidence? Trends and practice patterns from the National Cancer Database. First Author: Lauren E. Schleimer, Memorial Sloan Kettering Cancer Center, New York, NY Background: Intrahepatic cholangiocarcinoma (IHC) is often advanced at presentation. Mounting evidence suggests a limited role for surgical resection in the setting of multifocal hepatic and regional lymph node involvement in favor of initial treatment with systemic therapy. We sought to characterize trends and practice patterns in the management of patients with locally advanced IHC without distant extrahepatic metastasis. Over the last decade, increasing evidence has demonstrated unfavorable outcomes of surgical resection in locally advanced IHC even without distant extrahepatic disease, and supported the use of multimodality therapy. The most significant overall trends have been increasing use of perioperative systemic therapy in combination with formal resection compared to resection alone and an improvement in overall survival. On subgroup analysis, there was a significant and appropriate trend away from resection as first treatment modality for patients with clinically positive lymph nodes or multifocal disease. Research Sponsor: None.

1. Trosman, JCOOP 2021.2. Liu, JCOOP 2022.ResearchSponsor: Genentech. fractions, median dose of 40 Gy, and dose ranging from 16 Gy to 60 Gy. CRT was delivered in 13-28 fractions, median dose of 50.2 Gy, and dose ranging from 45 Gy to 52.5 Gy. Kaplan-Meier was used to analyze overall survival (OS), progression-free survival (PFS), and local control (LC). Acute and late G3+ toxicity was scored using CTCAE, version 5.0. Results: We identified 13 patients with ICC, 5 with ECC, and 13 with perihilar disease where SBRT or CRT was part of upfront definitive treatment. With a median follow-up time of 11 months, there was no statistical difference between SBRT vs. CRT for OS (median 21 vs.

Preoperative preoperative endoscopic nasal biliary drainage (ENBD) and/ or endoscopic retrograde biliary drainage (ERBD) procedures may affect the intrahepatic recurrence of tumor in patient with cholangiocarcinoma after surgical resection.And serum elevated CA 19-9 level affected intrahepatic recurrence of tumor in patients with cholangiocarcinoma after surgical resection.Research Sponsor: None.Promising first-line immuno-combination therapies for unresectable hepatocellular carcinoma: A cost-effectiveness analysis.First Author: Feng Wen, West China Hospital Sichuan University, Chengdu, China Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related death all over the world, bringing a heavy social economic burden especially in China.Several immuno-combination therapies have shown promising efficacy in the first-line treatment of unresectable HCC and are widely used in clinical practice.However, which combination is the most affordable is unknown.The current study assessed the cost-effectiveness of the immuno-combinations as first-line treatment for patients with unresectable HCC from the Chinese payers' perspective.Medical costs were searched from the Red Book, published literatures, and West China Hospital.Cost-effectiveness ratios (CERs) and incremental cost-effectiveness ratios (ICERs) were evaluated to compare costs among different combinations.Sensitivity analyses were performed to assess the robust of the model.Results: The total cost and quality-adjusted life years (QALYs) of C+R, S+B, P+L, A+B and STRIDE were $12,109.27and 0.91, $26,961.60 and 1.12, $55,382.53 and 0.83, $70,985.06 and 0.90, $84,589.01 and 0.73 respectively, resulting in the most cost-effective strategy of C+R with CER of $13,306.89 per QALY followed by S+B with CER of $24,072.86 per QALY.The S+B strategy would become the most cost-effective when the willing-to-pay threshold exceeded $73,500/QALY.In the subgroup analysis, with the application of Asia results in Leap-002 trial, the model results were the same as global data.In the sensitivity analysis, with the variation of parameters, the results were robust.Conclusions: As one of the promising immuno-combination therapies in the first-line systemic treatment for unresectable HCC, camrelizumab plus rivoceranib demonstrated the potential to be the most cost-effective strategy, which warranted further studies to best inform the realworld clinical practices.Research Sponsor: Med-X Center for Informatics, Sichuan University.Tinengotinib (TT-00420) in combination with atezolizumab in Chinese patients (pts) with biliary tract carcinoma (BTC): Preliminary efficacy and safety results from a phase Ib/II study. First Author: Panpan Zhang, Beijing Cancer Hospital, Beijing, China Background: Programmed Cell Death Ligand 1 (PD-L1) inhibitor durvalumab in combination with gemcitabine and cisplatin has been approved as first-line therapy for BTC. However, the efficacy of subsequent standard of care is limited. Tinengotinib is a spectrum-selective multi-kinase inhibitor that targets cell proliferation, angiogenesis, and immune-oncology pathways by inhibiting Aurora kinases A/B, Janus kinases and receptor tyrosine kinases (FGFRs and VEGFRs). Tinengotinib combined with PD-L1 has demonstrated promising antineoplastic activity in preclinical study. Here we present the preliminary data of tinengotinib in combination with atezolizumab (atezo) in pts with advanced BTC from a phase Ib/II trial in China. Methods: In combination therapy, eligible pts with advanced/metastatic BTC were enrolled and treated with tinengotinib plus atezo 1200 mg/20 mL in 21-day cycle. Dose escalation (Phase Ib) and dose expansion (Phase II) were designed. Dose escalation followed a standard 3+3 design.

First safety and efficacy data from phase Ib/IIa study of fostroxacitabine bralpamide (fostrox, MIV-818) in combination with lenvatinib in patients with hepatocellular carcinoma (HCC).First Author: Maria Reig, Hospital Provincial Clinic de Barcelona, Barcelona, Spain Background: Fostrox is an orally administered troxacitabine-based nucleotide prodrug in clinical development in combination with lenvatinib (NCT03781934).Fostrox is rapidly metabolized by human hepatocytes, directing high levels of the active metabolite to the liver.Phase I fostrox monotherapy demonstrated selective intra-tumoral activity in ontreatment liver biopsies.The anti-angiogenic activity of lenvatinib has the potential to synergize with fostrox by hypoxia-induced increase in the enzymatic generation of the active metabolite of fostrox in the tumor.Methods: In a phase Ib/IIa study with an interpatient dose escalation 3+3 cohort design followed by a dose expansion phase, fostrox was administered orally QD for 5 days in 21-day cycles in combination with lenvatinib according to local prescription information.Patients (pts) with ,2 prior lines systemic treatment for advanced, unresectable HCC were recruited at 10 sites in Spain, South Korea and UK.Pts with histologically, radiologically, or cytologically confirmed HCC, Child-Pugh A, $18 years, ECOG PS # 1 and adequate organ function were eligible.The primary objective was to assess safety and tolerability.Key secondary endpoints were ORR based on RECIST 1.1 and mRECIST.Exploratory endpoints included pharmacokinetics (PK) and pharmacodynamic effects of fostrox in combination with lenvatinib.Results: At interim data cut-off 18 pts (6 pts in Ib and 12 pts in IIa) were enrolled at fostrox QD doses of 20mg (3 pts) and 30mg (15 pts) in combination with lenvatinib.Median age was 63 years (range: 42-82).No DLTs and only 1 discontinuation of fostrox due to AEs with a median FU of 3.8 months, were observed.Most common grade 3/4 AEs were transient neutrophil count decrease, platelet count decrease and hypertension.No febrile neutropenia, bleeding events or proteinuria were reported.The safety profile was consistent with each individual agent.In phase Ib, central independent review based on RECIST 1.1 showed SD in 5/6 pts, while mRECIST showed CR in 1 pt, PR in 2 pts and SD in 2 pts.Updated phase Ib data and efficacy data from phase IIa by central independent review, together with PK for fostrox and lenvatinib, and liver biopsy biomarker data, will be presented.Conclusions: Fostrox in combination with lenvatinib, in pts with HCC who progressed on previous systemic treatment, had an acceptable safety and tolerability profile with promising interim efficacy results from the completely enrolled phase Ib/IIa study.Clinical trial information: NCT03781934.Research Sponsor: Medivir AB.Phase 2 REGONEXT trial.First Author: Changhoon Yoo, Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea Background: Atezo-Bev is the standard first-line therapy against uHCC.However, there is no globally established subsequent treatment after failure on first-line Atezo-Bev.We aimed to evaluate the efficacy and safety of second-line regorafenib in uHCC pts who progressed on first-line Atezo-Bev.Methods: This is a phase II investigator-initiated trial involving 2 academic centers in Korea.Key eligibility criteria include confirmed diag-Regorafenib was effective as second-line therapy in uHCC pts who progressed on first-line Atezo-Bev.Efficacy and safety outcomes from our study were consistent with those observed in the pivotal phase 3 RESORCE trial which included sorafenib-tolerated/progressed pts. Clinical trial information: NCT05134532. Research Sponsor: Bayer. This open label, multicenter phase II trial enrolled patients with histologically or clinically confirmed intermediate uHCC to receive TACE followed by cadonilimab 10mg/kg every 3 weeks plus Len until disease progression or intolerable toxicity. The primary endpoint was progression free disease (PFS) according to RECIST v1.1. The secondary endpoint includes safety, overall survival (OS), PFS according to modified RECIST (mRECIST), and objective response rate (ORR), disease control rate (DCR) and duration of response (DoR) by both RECIST v1.1 and mRECIST. Results: From June 2022 to May 2023, 78 patients were screened and 60 patients enrolled. As of August 15, 2023, 60 patients received at least once cadonilimab and the median duration of follow-up was 5.1 months. The average number of TACE procedures per patient was 1.70. The median PFS and OS were not reached, while the 6-month PFS rate was

Research Sponsor: Japan Agency for Medical Research and Development.Phase Ib trial of durvalumab plus tremelimumab in combination with particle therapy in advanced hepatocellular carcinoma patients with macrovascular invasion: DEPARTURE trial.First Author: Sadahisa Ogasawara, Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan Background: The HIMALAYA study established the efficacy and safety of durvalumab combined with tremelimumab (STRIDE) as a first-line treatment for advanced hepatocellular carcinoma (HCC).Carbon ion radiotherapy (C-ion RT), a type of particle therapy, allows precise tumor targeting while sparing nearby normal tissue.In HCC, macrovascular invasion (MVI) signifies aggressive progression with poor outcomes.Our strategy used C-ion RT to target a key tumor with MVI for disease management and potential MVI control, complemented by STRIDE.Recognizing that radiation therapies, including C-ion RT, stimulate immune responses, notably releasing tumor antigens and DAMPs (immune priming), we posited that merging C-ion RT with STRIDE might enhance therapeutic effects.Methods: This is a Phase Ib, multicenter study evaluating durvalumab with particle beam radiotherapy in HCC patients with MVI (Cohort A) and STRIDE (Cohort B).Both cohorts began with patients resistant to standard treatments.After safety confirmation, the study expanded to include systemic therapy-naïve patients, totaling 15.C-ion RT begins after day 8 of the first cycle, following the initial drug dose.The relative biological effectiveness weighted dose is set at 60 Gy in four fractions over one week, targeting one representative intrahepatic nodule with MVI.The primary endpoint is adverse event rates, including dose limiting toxicity (DLT), with secondary endpoints progression free survival (PFS) and overall survival (OS) (jRCT2031210046).Results: From July 2021 to January 2023, 15 advanced HCC patients were enrolled in our study (Cohort A: 3, Cohort B: 12).Four in Cohort B were systemic therapy-naïve.All cases confirmed MVI radiologically; with tumor invasion observed in the main portal vein for 4 patients and in the inferior vena cava for one.DLT evaluations in 3 from each cohort showed no incidents.While Cohort A had no adverse events, 4 patients in Cohort B (26.7%) experienced serious treatment-related adverse events.Cohort B's median PFS was a significant 2.79 months (95%CI, 1.12-6.64).The 6and 12-month PFS rates stood at 38.1% and 12.7% respectively.The median OS is still undetermined, but promisingly, the 6-and 12-month survival rates both reached 87.5%.Evaluating the safety and efficacy of the addition of liver radiation (RT) to atezolizumab and bevacizumab (A/B) in advanced hepatocellular carcinoma (HCC): A retrospective cohort analysis. First Author: Timothy J Brown, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX Background: Recently, the addition of stereotactic body RT to sorafenib in patients (pts) with advanced HCC demonstrated improved overall survival. However, A/B is the current standard of care for pts with advanced HCC based on IMBrave150. For these pts, RT may potentiate the antitumor immune response of A/B but carries the risk of bowel toxicity and impaired liver function. To date, there are limited data regarding safety and outcomes with the addition of liver RT to A/B in pts with advanced HCC. Here, we describe our single-center experience of adding RT to A/B for pts with advanced HCC. Methods: This single-center retrospective cohort study was conducted at the University of Pennsylvania.

mg/day if bodyweight [BW] ,60 kg; 12 mg/day if BW $60 kg) + pembro (200 mg IV Q3W) or len + pbo. Dual primary end points were OS and PFS (per RECIST v1.1 by BICR). Secondary end points included ORR and DOR, both per RECIST v1.1 by BICR, and safety. Data cutoff was June 6, 2023. Results: 794 pts were randomly assigned to receive len

Combinations of a PD-1/L1 inhibitor with a CTLA-4 or VEGF inhibitor have been approved as 1L treatment options for pts with advanced HCC. The multicenter, phase 2 KEYSTEP-004 study (NCT04740307) was conducted to evaluate the coformulation of quavonlimab (CTLA-4 inhibitor) and pembro (PD-1 inhibitor) in combination with lenva (multityrosine kinase inhibitor) as 1L treatment for pts with advanced HCC. Methods: Pts were $18 y of age, had histologically or radiographically confirmed HCC with no prior systemic therapy, and were not amenable to curative therapy; had Child-Pugh class A; and ECOG PS 0 or 1. The study consisted of a safety lead-in phase (approximately 6-20 pts) to evaluate the tolerability of the recommended phase 2 dose of lenva with a possibility of dose modification based on doselimiting toxicities (DLTs) and an efficacy expansion phase (approximately 110 pts). In the safety lead-in phase, pts received a fixed-dose coformulation of quavonlimab 25 mg and pembro 400 mg IV Q6W in combination with lenva 8 mg (body weight [BW] ,60 kg) or 12 mg (BW $60 kg) PO QD. Allocation to the efficacy expansion phase was allowed if the doses of lenva were determined to be tolerable. Primary end points were ORR per RECIST v1.1 by BICR and safety. Secondary end points included DOR, DCR, and PFS per RECIST v1.1 by BICR and OS. Results: No DLTs were observed in the 6 pts enrolled in the safety lead-in phase. 115 pts in the safety lead-in phase or the efficacy expansion phase were treated with the fixed-dose coformulation of quavonlimab and pembro plus lenva 8 or 12 mg. 94 pts (81.7%) were male, median age was 64 y (range, 32-83), and 80 pts (69.6%) had AFP #400 ng/mL. As of the June 22, 2023, data cutoff date, median follow-up (time from first dose to database cutoff date

The primary endpoint was R0 resection rate, and secondary endpoints included ORR, DCR, PFS, OS, CPR, MPR, RFS.Results: From December 2021 to July 2023, 41 pts were enrolled, 21 males and 20 females with a mean age of 57 years.87.8% pts had iCCA, 7.3% had perihilar bile duct cancer and 4.9% had gallbladder cancer.TNM stage was II, IIIA, IIIB and IIIC for 2.4%, 34.1%, 58.5% and 4.9% of pts respectively.At cut-off date (September 10, 2023), the mean follow-up was 7.7 months, 39 pts completed at least three cycles of conversion therapy and 7 pts still administered with scheduled conversion therapy.The ORR was 43.9% (18/41) and the DCR was 87.8% (36/41).The median duration of therapy before surgery was 2.AEs occurred.Conclusions: This study demonstrates the high effectiveness and manageable safety of GOLP regimen as conversion therapy for potentially resectable locally advanced BTC.Survival data will continue to be followed up.Clinical trial information: NCT05156788.Research Sponsor: None.Efficacy and safety of a combination of sintilimab, bevacizumab plus gemcitabine, and albumin-bound paclitaxel for initially unresectable gallbladder carcinoma: A prospective, single-arm phase II study. First Author: Miao Wang, Liver Surgery Department, Shanghai Cancer Center, Shanghai, China Background: Immune checkpoint inhibitors plus chemotherapy had demonstrated important therapeutic advantages in biliary tract cancers (TOP-AZ and Keynote-966). At present the data of gallbladder carcinoma (GBC) is in blank condition almost, and the effectiveness remains to be improved. Further, the addition of bevacizumab to PD-1 inhibitors has improved the clinical results in carcinomas, such as hepatocellular carcinoma, for which therapeutic options have been limited. This study intended to explore the safety and efficacy of sintilimab combined bevacizumab with chemotherapy in the first-line treatment of initially unresectable GBC. No DLT was reported at safety-run-in part. Up to the end of Sept 2023, 15 patients were enrolled with a median age of 60.4 years (range 46-75), 26.7% were male. Median follow-up time was 3.68 months. All patients completed at least one tumor response evaluation, confirmed ORR was 60.0% and DCR was 93.3%. Median PFS and OS was not reached yet. Grade 3 TRAEs occurred in 40.0% of patients (

Background: A subset of biliary tract cancers (BTC) feature amplification (amp) of the human epidermal growth factor receptor 2 (ERBB2) gene.The prognostic role and treatment in these patients (pts) are poorly understood.This study aims to characterize the clinical outcomes and molecular profiles of ERBB2-amp BTC.Methods: We conducted a retrospective analysis of clinical outcomes data and next-generation sequencing (NGS) at MD Anderson (MDA) and Foundation Medicine (FMI) from 2009-2023 in pts with ERBB2-amp BTC including all classes of genomic alterations (GA) in other genes.Progression-free survival (PFS) and overall survival (OS) were assessed by the log-rank test.Results: 80 pts (MDA) were identified with ERBB2amp BTC with documented treatment and NGS data.Pts (Table)who received ERBB2-directed ERBB2-amp BTC has shorter mPFS or mOS without ERBB2-directed therapy, surgery, or local therapy, suggesting clinical benefit from multi-disciplinary care and targeted therapy.Co-GA with ERBB2-amp did not demonstrate a significant association with survival outcomes.Research Sponsor: None.Comparison of the treatment effect between lenvatinib and atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma in pathologically diagnosed metabolic dysfunction-associated steatotic liver disease. First Author: Hirokazu Takahashi, Liver Center, Saga University Hospital, Saga, Japan Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the leading etiologies of HCC. Recent evidence indicates that MASLD might affect the response to immune checkpoint inhibitors and multi-receptor tyrosine kinase inhibitors in the treatment for unresectable hepatocellular carcinoma (HCC), yet real-world data with accurate pathological diagnosis of MASLD has not been confirmed. Methods: Patients with unresectable HCC who had been pathologically diagnosed with MASLD by liver biopsy and/or hepatectomy and later received treatment with lenvatinib (LEN) or atezolizumab plus bevacizumab (ATZ/Bev) as first-line systemic treatment for HCC were included. Outcomes of treatment with LEN or ATZ/Bev were compared. Results: A total of 48 patients who received LEN (n=26) and ATZ/Bev (n=22) were included. The mean time from pathological diagnosis to the initiation of treatment was not different (LEN 1,542 days, ATZ/Bev 1,260 days; p=0.48). The degree of steatosis, inflammation, ballooning hepatocytes and fibrosis did not differ between LEN and ATZ/ Bev. At the initiation of treatment, BCLC stage, albumin-bilirubin grade, and Child-Pugh grade did not differ between LEN and ATZ/Bev. The overall response rate and disease control rate evaluated with modified RECIST criteria were not different between LEN and ATZ/Bev (26.1% and 77.2% for LEN, and 22.7% and 70.8% for ATZ/Bev). Median progression-free survival (PFS) was not different between LEN and ATZ/Bev (266 days vs 287 days, p=0.278). Median overall survival (OS) of LEN tended to be longer than that of ATZ/Bev (1364 days vs 663 days, p=0.081). The potential advantage of LEN in OS was statistically significant in the patients with Child-Pugh score = 5 (P=0.0443). A total of 17 patients received both LEN and ATZ/Bev treatment and order of the treatment did not associate with PFS and OS. Conclusions: Outcomes of LEN and ATZ/Bev treatment for advanced HCC were not different in pathologically confirmed MASLD. Longer OS of LEN than ATZ/Bev was observed in the patients with relatively better liver function, suggesting that LEN might be a suitable first-line treatment for HCC with compensated liver function in the patients with pathologically confirmed MASLD. Research Sponsor: None.

Treatment was repeated until tumor progression or unacceptable toxicity were observed.Results: A total of 140 patients (40 in the Lenva+CDDP group and 100 in the lenvatinib group) were included in this analysis.Patient backgrounds were comparable between the two groups, and 12 and 19 patients were previously treated with immunotherapy in the Lenva+CDDP group and lenvatinib group, respectively.The objective response rate and tumor control rate, assessed by RECIST ver1.1, in the Lenva+CDDP group were 67.5% and 100%, respectively, which was higher than in the lenvatinib group (17.0% and 87.0%, respectively).Median progression-free survival (PFS) and overall survival (OS) were 8.8 months and 19.6 months, respectively, in the Lenva+CDDP group, and 5.6 months and 20.3 months, respectively, in the lenvatinib group.Among patients who previously received immunotherapy, the median PFS, median OS, and 1-year survival rate were 9.7 months, not reached, and 87.5%, respectively, in the Lenva+CDDP group, and 4.7 months, 15.8 months, and 64.7%, respectively, in the lenvatinib group.Hematological toxicities were the main grade 3-4 adverse events (AEs) more frequently observed in the Lenva+CDDP group compared with the lenvatinib group.However, all grade 3-4 AEs were reversible, and there were no treatment-related deaths in either group.Conclusions: Lenva+CDDP demonstrated a better response and patient outcome than lenvatinib, and was well-tolerated in patients with advanced HCC.We are currently conducting a randomized controlled trial comparing the efficacy of these treatments.Research Sponsor: None.Anlotinib plus TQB2450 (PD-L1 blockade) combined with nab-paclitaxel and cisplatin as first-line treatment for advanced biliary tract cancer: A singlearm, open-label phase II clinical trial. First Author: Shui-Ling Jin, Department of Medical Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

Initial uptake of durvalumab with or without tremelimumab for advanced hepatocellular carcinoma in routine clinical practice: Preliminary results of the international DT-real study. First Author: Ciro Celsa, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, United Kingdom Background: HIMALAYA trial showed that durvalumab plus tremelimumab (Single Tremelimumab Regular Interval Durvalumab; STRIDE) significantly improved overall survival (OS) and that durvalumab (DUR) was non-inferior compared to sorafenib in patients with hepatocellular carcinoma (HCC). However, real world outcomes on this regimen have not been described. Methods: In the context of a prospectively maintained database including 953 patients (pts) with unresectable HCC treated with immunotherapy, we analysed a subgroup of pts treated with STRIDE or DUR across 5 centres in USA, Asia and Europe. We assessed OS, progression-free survival (PFS), objective re-Preliminary observational data from DT-real confirm uptake of STRIDE and DUR across various lines of therapy, with encouraging efficacy and safety outcomes in routine practice. Research Sponsor: None.

This study is the first to qualify the role of MPR as a putative surrogate endpoint for recurrence-free survival in pts treated with neoadjuvant immunotherapy for HCC. Validation in larger phase III clinical trials is warranted. Research Sponsor: None.

Impact of baseline ALBI grade and CP class on survival and other outcomes in Study CARES-310.

Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 29 and statistical significance was set at a = 0.05. Results: Of the 803 patients in the sample,19 patients received Local Tumor Destruction (LTD) and 142 patients received Wedge or Segmental Resection (WSR). The average age of patients receiving LTD was 54 compared to 32 for WSR. WSR patients experienced longer overall survival than LTD (106 vs. 63 months respectively; p,0.05). When controlling for age, year of diagnosis, tumor size, comorbidity score, and surgery type, WSR showed a greater decrease in overall hazard compared to LTD (HR=0.224 vs 0.306; p,0.05). WSR use was highest in healthy patients with no co-morbidities, however, patients were also significantly more likely to have later stage tumors (II, III, and IV vs. stage I; p,0.001). Despite being associated with a lower OS, LTD was utilized more commonly for earlier stage (stage I vs.

£14,481)versus ATEZO+BEV and LEN, respectively. Conclusions: A sequence of SOR-REG for patients with advanced HCC is cost-effective at WTP thresholds of £30,000 / QALY gained due to lower lifetime costs and broadly comparable QALY gains with single-line ATEZO-BEV and LEN in the UK. Broader second-line treatment options are needed for patients receiving ATEZO+BEV and LEN as firstline therapies. Research Sponsor: Bayer Pharmaceuticals.

Association of FGFR2 structural alterations in intrahepatic cholangiocarcinomas with female gender and younger age. First Author: Zishuo Ian Hu, Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX Background: FGFR2 fusions and other rearrangements are targetable alterations due to the advent of FGFR2 kinase domain inhibitors, and are considerably more common in intrahepatic cholangiocarcinomas (iCCA) than other cancer types. Understanding clinical factors associated with FGFR2 fusions and other rearrangements may guide precision oncology efforts. Prior studies indicate that FGFR2 alterations are more common in younger patients, but it remains unknown whether other demographics are specifically associated with FGFR2 structural alterations.

First Author: Colin P Bergstrom, Stanford University Medical Center, Stanford, CA Background: Cholangiocarcinoma (CCA) has poor prognosis and limited treatment options. The US Veteran Health Administration's (VHA) National Precision Oncology Program (NPOP) was established to characterize pathogenic drivers across the integrated VA network. Here, we summarize an important subgroup of CCA with homologous recombination deficiency (HRD) and its impact on overall survival (OS). Methods: Next-generation sequencing (NGS) was performed using FoundationOne CDx Analysis included clinicopathological, molecular alterations including, single nucleotide variants, gene amplification/loss, and gene fusion/ rearrangements obtained from centralized data of the VHA's Corporate Data Warehouse. KRAS MT (n=77, 15.9% of population) did not impact OS (WT 12.3 mo v. MT 13.1 mo) including subgroup analysis stratified by HRD status. There was increased frequency in KRAS MT with HRD WT 18.5% versus HRD MT10.4% (p,0.03). Additionally, there was increased frequency in TP53 MT with HRD WT 54.8% versus HRD MT 28.1% (p,0.00001). TP53 MT (n=224, 46.3% of population) conferred inferior OS (WT 12.3 mo v. MT 13.1 mo) including subgroup analysis stratified by HRD status. Subgroup analysis of TP53 MT had worsened OS with concurrent HRD MT (n=39, 4.1 mo) v. HRD WT (n=158, 9.0 mo; p,0.04). Conclusions: Across a diverse integrated healthcare system of Veterans, mutations associated with HRD were found to be common, however, not prognostic in OS across a diverse patient population of CCA. Further work is needed to clarify exposure to platinum containing chemotherapy. TP53 MT CCA remains a critical unmet need that drives worsened outcomes including here in patients with mutations in HRD. Future analysis should consider mutation signatures of HRD, loss in heterozygosity of HRD, and platinum exposure to further define the subgroups of CCA with mutations in HRD. Research Sponsor: None.

Cholangiocarcinoma (CCA) requires integrated efforts to understand the heterogeneity in available molecular targets. Chemotherapy remains a non-selective standard of care, however defining distinct populations with molecular actionability remains a critical need. The Veteran Health Administration's (VHA) National Precision Oncology Program (NPOP) was established to characterize comprehensive genomic profiles across the integrated VHA network. Methods: Veterans with CCA underwent next-generation sequencing (NGS) with FoundationOne CDx, which enhanced sensitivity in the reporting of gene fusions. Analysis included dedicated chart review for date of diagnosis and survival utilizing the VHA's Corporate Data Warehouse. Molecular alterations included mutations(mut), amplifications (amp) and fusion/rearrangements (fus). Log-rank Kaplan-Meier survival analysis was stratified by primary tumor location, and actionable driver alterations defined by VA Clinical Pathways. Across an integrated healthcare system of Veterans, actionable molecular alterations from VA Pathways were seen in 21.1% of the population. Further data is needed to clarify the prognostic versus predictive value of integrated precision-based strategies in clinical practice. The Veteran population includes important molecular subtypes to consider in future prospective trial design. Research Sponsor: None.

Artificial intelligence (AI)-powered tumor microenvironment (TME) analysis to identify potential biomarkers for ICIs with or without bevacizumab in hepatocellular carcinoma (HCC). First Author: Hong Jae Chon, Department of Medical Oncology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, South Korea Background: While immunotherapies have been approved for use in HCC patients, there is a need for validated predictive biomarkers that correlate with treatment outcomes. We investigated whether AI-powered spatial analysis of non-cancerous cells within the TME can be potential biomarkers for ICIs with or without bevacizumab in advanced HCC. Methods: Analysis of images of H & E-stained slides was conducted by an AI model, Lunit SCOPE IO in pre-treatment tumor samples of 163 HCC patients treated with atezolizumab plus bevacizumab as first-line (n=82), or monotherapies of nivolumab or pembrolizumab as $ second-line (n=81) at CHA Bundang Medical Center or Samsung Medical Center. We analyzed the correlation between clinical outcomes after the treatment and AI-powered TME-related variables, including TILs and endothelial cells, within intratumoral or stromal areas. Inflamed immune phenotype (IIP) was defined as cases exhibiting enrichment of intratumoral TILs. Results: Baseline characteristics, including Child-Pugh liver classification, Barcelona Clinic Liver Cancer stage, and hepatitis B virus, were well-balanced between treatment regimens. IIP was predictive of longer progression-free survival (PFS) of nivolumab or pembrolizumab monotherapy (median PFS 4.7 months for IIP vs. 2.2 months for non-IIP; hazard ratio [HR] 0.50; 95% confidence interval [CI] 0.25-0.99; p=0.042), but not PFS of atezolizumab plus bevacizumab (median PFS 6.8 months vs. 6.2 months; HR 0.92; 95% CI 0.50-1.69; p=0.762). PFS of atezolizumab plus bevacizumab was significantly longer in cases harboring intratumoral endothelial cell density in the highest quartile (median PFS 6.7 months for upper 25% vs. 3.9 months for lower 75%; HR 0.51; 95% CI 0.27-0.97; p=0.037), while there was no significant difference in PFS of pembrolizumab or nivolumab monotherapy (median PFS 2.3 months vs. 2.8 months; HR 1.02; 95% CI 0.59-1.77; p=0.935). Conclusions: AI-powered TME analysis shows IIP is predictive of longer PFS with ICI monotherapies, whereas intratumoral endothelial cell density is specifically associated with PFS of atezolizumab plus bevacizumab in advanced HCC. The latter finding may suggest efficacy of combined VEGFRi and ICI activity is dependent on the amount of baseline tumor vasculature. Research Sponsor: None.

Developing a comprehensive cell-free DNA (cfDNA) epigenetic signature (ep-Sig) with diagnostic and prognostic value in hepatocellular carcinoma (HCC). First Author: Ashish Manne, The Ohio State University Comprehensive Cancer Center, Columbus, OH

P=0.002).No other clinicopathologic or genomic variables distinguished PCA from DCA (Table).MDM2mut occurred in 19/141 (13%) patients with nodal/metastatic disease compared to 1/83 (1%) patients with local disease (Q=0.03),butconferred no survival disadvantage.In resected patients, survival was similar between PCA and DCA and no genomic alterations were associated with outcome.By contrast, in patients without surgery, CDKN2Adel (HR 2.59, 95% CI [1.48, 4.52]) and APCmut (HR 5.11, 95% CI [1.96, 13.3] ) were associated with survival disadvantages.Lack of resection (HR 3.13, 95% CI [2.25, 4.36]), CDKN2Amut (HR 1.80 [95% CI 1.80, 2.68), and APCmut (HR 2.00 [95% CI 1.04, 3.87] ) were associated with poor survival in the entire cohort. Conclusions: In this study, aside from a higher incidence of TP53mut in DCA and some differences in KRAS subtype alteration patterns, genomic alterations were comparable between PCA and DCA. CDKN2Amut and APCmut were associated with poor survival in all patients but no biomarkers provided significant prognostic information when tumors were resected. Research Sponsor: None.

Hepatocellular carcinoma (HCC), the predominant form of hepatic cancer is associated with high mortality rates, both in the United States & globally. Alpha-fetoprotein (AFP) & Glypican-3 have been proposed as biomarkers for HCC, although they do not offer any prognostic benefit to model disease progression. Immunotherapy combinations increase patient survival to ~18 months but are not selected based on biomarkers. Agrin, a secreted proteoglycan is frequently overexpressed & secreted in HCC & plays a prominent role in liver tumor microenvironment to promote hepatocarcinogenesis. In this single center, retrospective study using banked materials, we assessed the role of agrin as a prognostic biomarker in HCC. Methods: With IRB approval, we studied 90 newly diagnosed unresectable hepatobiliary cancer patients, & compared them to healthy controls matched for age, gender, & BMI between February 2006 & September 2013. Serum concentration (conc.) of agrin was assessed using enzyme-linked immunosorbent assay (ELISA). We correlated the level of agrin with AFP, a known biomarker in hepatocellular cancer. Comparisons between groups were made using Mann-Whitney U & Kruskal Wallis tests. Survival analysis used both univariate & multivariate Cox regression models to investigate the relationship between survival outcomes & agrin concentration, in comparison to AFP.

87 in subsequent-line settings can guide sample size calculation in future clinical trials. Research Sponsor: None.

Multivariable logistic regression analysis was performed to assess the association of HCC with obesity and inpatient mortality adjusted by age, gender, race, Charlson index, insurance, and household income.Results: A total of 62,050 HCC patients were identified, and 10.9% of these patients had obesity.HCC patients with obesity were younger (64.7 vs. 65 years, p=0.220), more likely to be female (32.2% vs. 24%, p , 0.001), White (59.8% vs. 50.2%p, 0.001), and more likely to have no insurance (28.8% vs. 23.3%,p, 0.001) compared to HCC patients without obesity.HCC with obesity had higher mean Charlson Comorbidity index 5.9 vs. 5.5, p , 0.001).The overall inpatient mortality rate was 8.2% for all patients who are admitted for HCC; lower in HCC with obesity (5.6%) vs HCC without obesity (8.5%) (p , 0.001).Charlson index, Male gender, African-American race, Hospital teaching status, insurance status found to be associated with inpatient mortality among HCC hospitalizations.HCC with obesity had a lower odds ratio with decreased all-cause mortality of 25% compared to HCC without obesity (aOR 0.75, 95% CI 0.58-0.96,p= 0.023).In addition, HCC with obesity was associated with increased LOS mean 6.3 vs. 5.7 days (adjusted difference: 0.6 p , 0.001), and total hospital charges (mean $112,687 vs $88,481, adjusted difference: $21122 p , 0.0001).Also; ICU transfer rate and AKI development were found more in obese cohort and this different was statistically significant.Conclusions: Our study revealed that HCC patients with obesity had a lower inpatient mortality rate compared to those without obesity, despite longer hospital stays and higher costs.These findings hint at a complex interplay between obesity and HCC outcomes, necessitating further in-depth research.Research Sponsor: None.First Author: Pratik Chandra, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY Background: Recurrence is common after resection of intrahepatic cholangiocarcinoma (IHC) but how recurrence patterns impact survival remains unclear.This study investigated the clinicopathologic and genomic factors associated with site of first recurrence and their impact on outcome after curative intent resection.Methods: Patients who underwent curative intent hepatectomy for IHC at two medical centers (MSKCC and EMC) with complete follow up and tumor genomic data were included.Documented sites of first disease recurrence were classified as liver only (LO), extrahepatic (EH) only or simultaneous liver and extrahepatic (SIM)., 0.001) were independent predictors of worse OS.Of note, 13 LO patients were treated with regional chemotherapy after recurrence, with an associated median OS of 49 (33, NR) months compared to 28 (20, 39) months in the 80 patients treated with systemic therapy alone.Conclusions: Recurrence after resection of IHC was common, and the liver was the single most common site (66%).Clinicopathologic and genomic variables had limited ability to predict site of first recurrence.While LO and EH were associated with similar OS, simultaneous recurrences were dramatically worse.The data support adjuvant strategies targeting liver recurrence to improve outcome after resection of IHC.Research Sponsor: None.Viral hepatitis (HBV and HCV), and lifestyle factors (tobacco chewing and pipe-smoking) were strongly associated with HCC.Further research should explore the role of tobacco chewing and pipe-smoking in HCC risk in Uganda and similar settings in Sub-Saharan Africa.Research Sponsor: None.Other secondary endpoints are progression-free survival, overall survival, safety, and quality of life.Sample size (120 patients) was estimated on the assumption that if the lower ORR between futibatinib 16 mg and 20 mg is 32% (with $60 patients per arm), the probability of correctly selecting the treatment arm with a true ORR of 42% is 0.87.Enrollment is ongoing in Europe, the US, and Asia-Pacific.1.Goyal L et al.N Engl J Med. 2023;388:228-39.2. Meric-Bernstam F et al.Cancer Discov.2022;12:402-15. Clinical trial information: NCT05727176. Research Sponsor: Taiho Oncology, Inc. Fibrolamellar carcinoma (FLC) is a rare, aggressive form of primary liver cancer predominantly affecting children and young adults under the age of 30. There is no established standard therapy and most patients with advanced disease succumb to their illness with a median prognosis of only 12 months. A chimeric transcript between DNAJB1 and PRKACA, which encodes the catalytic subunit of protein kinase A (PKA), was identified as a signature genomic event in FLC. However, pharmacological inhibition of PKAc for FLC with traditional small molecule inhibitors has been infeasible due to unacceptable on-target toxicity. Preclinical work from our laboratory and others has revealed that the DNAJB1-PRKACA fusion results in a metabolic rewiring of the tumor characterized by glutamine dependence. This glutamine dependence also creates a nutrient-depleted tumor immune microenvironment (TiME) enriched in immunosuppressive metabolites (e.g., ammonia, acidosis) that prohibits an effective antitumor immune response. Through this trial, we will test the hypothesis that glutamine antagonism in FLC reverses resistance to immune checkpoint inhibitor (ICI) therapy through modulating the TiME. Methods: We are conducting a single-arm phase 1b/2 clinical trial of glutamine antagonist DRP-104 in combination with durvalumab in children (age $ 12) and adults with advanced FLC who have progressed on prior anti-PD(L)1 therapy. Patients will receive DRP-104 (145 mg s.c. twice weekly) in combination with a fixed dose of durvalumab (1500 mg i.v. every 28 days). The primary clinical endpoints are safety and objective response rate (ORR), defined as the percentage of patients achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Secondary objectives include progression free survival (PFS), overall survival (OS), and immunological correlates. Key eligibility criteria include histologically confirmed FLC that is metastatic or unresectable; demonstrated radiographic progression on at least one line of prior anti-PD(L)1 therapy; Age $ 12 years; ECOG performance status of #2; measurable disease according to RECIST 1.1; and adequate end organ function. Patients will undergo fresh core tumor biopsy pre-treatment and at approximately week 4. Biopsies will be used to prepare paraffin embedded and flash-frozen samples. Research bloodwork will be collected prior to dosing at baseline, prior to dosing on cycles 2-5, and every 3 months thereafter to be processed for PBMC isolation. This study has been registered under NCT06027086 and is expected to begin enrollment in December 2023. Clinical trial information: NCT06027086. Research Sponsor: None.

). Methods: The MONTBLANC study is a randomized, 2-arm phase II study on the efficacy of combinations of durvalumab, tremelimumab, and bevacizumab in patients with advanced HCC.Patients with preserved liver function (Child-Pugh A) with unresectable tumors or not amenable to local or locoregional treatment are randomized to an early escalation arm (A) or a triple treatment arm (B).Patients in arm A receive combined durvalumab and tremelimumab (STRIDE regimen).Treatment is escalated by the addition of bevacizumab upon detection of disease progression or in the absence of radiological response by the 4th month of treatment.Patients in arm B receive up-front STRIDE and bevacizumab.Treatment will continue until unacceptable toxicity or progression under the Bevcontaining regimen.The primary endpoint is overall response rate (ORR).Clinical trial information: NCT05844046.Research Sponsor: None.Tinengotinib will be administered orally QD in 28-day cycles.Subjects will continue to receive study treatment until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or termination of study by Sponsor, whichever occurs first.For Part A, the primary endpoint is safety/tolerability; secondary endpoints include objective response rate (ORR), duration of response (DOR) and PK analysis.For Part B, the primary endpoint is progression-free survival (PFS); secondary endpoints include overall survival (OS), ORR, DOR, safety, quality of life and population PK.Exploratory endpoints will assess the correlations between baseline FGFR2 alterations by cfDNA and efficacy, and exposureresponse in terms of efficacy and safety.Study is open for enrollment.Clinical trial information: NCT05948475.Research Sponsor: None.The primary endpoint is the overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.Secondary endpoints are safety, ORR using HCC modified RECIST, duration of response, complete response rate, and progression-free survival.Clinical trial information: NCT05733598.Research Sponsor: Replimune, Inc.A phase 1b/2 study to evaluate the safety and efficacy of TTI-101 as monotherapy and in combination in advanced hepatocellular carcinoma.First Author: Farshid Dayyani, Division of Hematology/Oncology, Department of Medicine, University of California, Irvine, Orange, CA Background: STAT3 (signal transducer and activator of transcription 3) is a key regulatory protein positioned at the intersection of many signaling pathways integral to the survival and immune evasion of cancer cells.Persistent STAT3 activation has been linked to pathological conditions, including chronic inflammation and fibrosis, both of which play essential roles in the pathogenesis of hepatocellular carcinoma (HCC), and is Methods: NCT05440708 is a multicenter, open-label, study with primary endpoints including safety and efficacy of TTI-101 as monotherapy and in combination with SOC agents. Patients are enrolled to one of three treatment cohorts based upon prior therapy.Cohort A: TTI-101 (monotherapy), pts who have received up to 3 prior lines of systemic therapy.Cohort B: TTI-101 + pembrolizumab, pts who have progressed following $ 2 cycles of first-line anti-PD-(L)1 based therapy.Cohort C: TTI-101 + atezolizumab/bevacizumab, patients who are systemic treatment-naïve.The study consists of 2 parts for each cohort (Phase 1b and Phase 2).During Phase 1b, up to 3 dose levels of TTI-101 will be tested for each cohort to determine the RP2D, using a 3+3 design.Subsequent to RP2D determination, enrollment to Phase 2 will commence (Cohort A n=30, Cohort B n=30, Cohort C n=40).Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, discontinuation based on investigator discretion, or study termination.Secondary and exploratory endpoints include pharmacodynamic effects of TTI-101 and evaluation of candidate biomarkers for anti-tumor activity.Enrollment is simultaneously ongoing in Cohorts A, B, and C of the Phase 1b study.1. Jung KH, et al.Clin Cancer Res.2017;23(18):5537-5546.2. Zhao Y, et al.Hepatology.2021.Clinical trial information: NCT05440708.Research Sponsor: Tvardi Therapeutics.Lenvatinib in recurrent hepatocellular carcinoma after liver transplantation.First Author: Mehmet Akce, Division of Hematology/Oncology, University of Alabama at Birmingham, Birmingham, AL Background: Liver transplantation is a curative treatment option in hepatocellular carcinoma (HCC) however; up to 20% of patients develop recurrent disease.HCC recurrence post-transplant is usually extrahepatic (up to 67%) hence requires effective systemic therapy options.Available data are limited and restricted to small nonrandomized studies and case series.Lack of prospective clinical trial data and limited data indicates an area of unmet need in treatment of recurrent HCC after liver transplantation.This phase II study aims evaluate the safety and efficacy of lenvatinib in patients with recurrent HCC after liver transplantation.Methods: This is a multiinstitutional phase II trial with lenvatinib in patients with recurrent HCC after transplantation.Lenvatinib is administered 12 mg daily orally in patients $60 kg, and 8 mg daily orally in patients ,60 kg.Each cycle is 28 days.Restaging scans will be performed every 8 weeks.Eligible patients must have histologically proven HCC that has recurred after liver transplantation and not amenable for surgical resection, age $18 years, ECOG PS 0-1, Child Pugh Class A, measurable disease per RECIST version 1.1, adequate organ function, no prior systemic therapy with lenvatinib or another systemic therapy in the post-transplant setting.Prior liver directed therapy is allowed, should be at least .28days prior to the study enrollment, and should have at least one measurable untreated lesion by RECIST 1.1 Primary endpoint is overall response rate (ORR).Secondary endpoints are safety/tolerability, progression free survival, and overall survival. Pre-treatment and on-treatment peripheral blood samples will be collected for correlative research. A Simon`s two stage Minimax design is employed (H 0 : ORR = 5%; H 1 : ORR = 24%; Type I error = 0.05; power = 80%). In the first stage, 11 patients will be accrued, and if there is no objective response among them, the study will be stopped for futility. Otherwise, additional 6 patients will be accrued for a total of 17 patients. This study is currently enrolling patients. Clinical trial information: NCT05103904. Research Sponsor: None.

Phase I/II clinical trial of regorafenib plus durvalumab (MEDI4736) in patients with chemotherapy-refractory advanced biliary tract cancers.First Author: Raed Moh'd Taiseer Al-Rajabi, University of Kansas Cancer Center, Westwood, KS Background: Biliary tract cancers (BTC) are a heterogeneous group of cancers affecting the epithelial lining of the intra-and extrahepatic portions of the biliary tree, ranking as the second most prevalent primary liver cancer after hepatocellular carcinoma.A subgroup of BTC was found to have an abundant tumor specific neoantigen expression, enriched expression of immune related genes and genes regulating inhibitory immune checkpoint proteins.Recent advancements in BTC treatment include the TOPZ-1 trial, which established the survival advantage of adding durvalumab to the gemzar + cisplatin regimen with an estimated 24-month overall survival rate of 24.9% versus 10.4% for placebo.The hazard ratio for progression-free survival favored durvalumab at 0.75 (95% CI, 0.63 to 0.89; P=0.001).Objective response rates also showed improvement, with 26.7% for durvalumab and 18.7% for placebo.Furthermore, single agent regorafenib has exhibited efficacy in patients with refractory advanced metastatic cholangiocarcinoma, particularly in terms of progression-free survival, favoring regorafenib over placebo, the overall toxicity profile was as expected.Regorafenib targets multiple tyrosine kinases and has been reported to show immunomodulatory properties that may counteract tumor-induced immunosuppression, providing a rationale for combining it with checkpoint inhibitors.We believe that modulating the tumor microenvironment with small molecule inhibitors like regorafenib will have synergistic effect when combined with checkpoint-based immunotherapy like durvalumab in patients with chemo refractory BTC. Methods: This study comprises a single-arm, unblinded Phase I/II trial designed to assess the safety and efficacy of the combination therapy involving regorafenib and durvalumab in patients with chemo-refractory advanced BTC.The Phase I portion employed a 3 + 3 design with two dose levels of regorafenib (80 mg and 120 mg) administered in conjunction with 1500 mg IV durvalumab every 28 days.Phase I successfully completed, and the Data Monitoring Committee (DMC) endorsed the continuation of the trial as planned.Eligibility: Histologically confirmed unresectable or metastatic disease.Progressed on at least one line of therapy.May have received checkpoint inhibitor in the past.Inclusion criteria also include ECOG PS 0-1.Objectives: Primary Phase I: Safety of regorafenib in combination with durvalumab.Phase II: Progression-free survival (PFS).Secondary:Disease Control Rate (DCR), Overall response rate (ORR), Overall survival (OS).Statistical Plan: Interim futility testing after one year, halting if conditional power , 20%.Final analysis: PFS and OS via Weibull Regression.Enrollment is currently ongoing with 8 out of 40 patients enrolled.Research Sponsor: Bayer and AstraZeneca.phase II study to evaluate the safety and efficacy of anlotinib combined with penpulimab for advanced refractory biliary tract cancer.First Author: Xiaojun He, General Surgery Department, The Second Affiliate Hospital of Air Force Medical University/Tangdu Hospital, Xi'an, ChinaBackground: Although with modest efficacy, mFOLFOX is recommended as standard second-line chemotherapy for advanced biliary tract cancer (BTC). Several clinical trials are exploring the combination treatment of antiangiogenic drugs and immune checkpoint inhibitors. Anlotinib is an oral multi-targeted tyrosine kinase inhibitor tar-

PRECISION 1: A phase 2, multicenter, open-label basket trial of nab-sirolimus for malignant solid tumors harboring pathogenic inactivating alterations in TSC1 and TSC2.First Author: Dustin A. Deming, University of Wisconsin Carbone Cancer Center, Madison, WI Background: SEER data report that US patients with advanced gastrointestinal (GI) cancers have a poor prognosis as indicated by low 5-year survival rates in patients with colorectal (15.6%), liver (3.5%), and other GI cancers, highlighting the need for more efficacious treatments.Dysregulation of the mTOR pathway contributes to tumor growth and disease progression in many cancers, including GI cancers.The tumor suppressor genes TSC1 and TSC2 are critical negative regulators of mTOR activity whose inactivation can lead to tumor cell growth.Inactivating TSC1 and TSC2 alterations have been observed in GI cancers with a combined frequency of up to 6.5% in hepatocellular carcinoma, 1.7% in colorectal adenocarcinoma and gastrointestinal stromal tumors, and 1.6% in cholangiocarcinoma.nab-Sirolimus,approved in the US for patients with advanced malignant perivascular epithelioid cell tumor (PEComa), is an albumin-bound mTOR inhibitor (mTORi) that inhibits the mTOR pathway via suppression of the mTORC1 complex.In an exploratory analysis of the pivotal AMPECT trial of nab-sirolimus in advanced malignant PEComa (NCT02494570), 8/9 (89%) and 1/5 (20%) patients with inactivating alterations in TSC2 and TSC1, respectively, had a confirmed response.Most treatment-related adverse events were grade 1/2 (none were grade $4) and were consistent with mTORi-class adverse events.Based on the clinical observations from AMPECT and the underlying mechanism of action of nab-sirolimus, the PRECISION 1 trial was designed to assess the safety and efficacy of nab-sirolimus in a tumor-agnostic study of patients with advanced cancers harboring TSC1 or TSC2 inactivating alterations.The trial is open to patients with GI cancers with inactivating alterations in TSC1 or TSC2.Methods: In PRECISION 1 (NCT05103358), eligible patients are $12 years old and mTORi-naïve, have advanced malignant solid tumors harboring TSC1 or TSC2 inactivating alterations identified using next-generation sequencing (NGS) of tumor tissue or liquid biopsy (confirmed by central review of NGS reports), and have received appropriate standard treatments, per investigator.nab-Sirolimus100 mg/m 2 is given intravenously over 30 min on days 1 and 8 of each 21-day cycle.The primary endpoint is overall response rate per independent radiographic review (IRR) using Response Evaluation Criteria in Solid Tumors v1.1.Other endpoints include duration of response, time to response, progressionfree survival by IRR, overall survival, patient-reported quality of life, and safety.Enrollment began in March 2022.Collaboration with leading NGS vendors is expediting the identification of patients with qualifying TSC1 and TSC2 alterations; ongoing study access is facilitated through a just-in-time approach to trial location activation.Clinical trial information: NCT05103358.Research Sponsor: Aadi Bioscience.Phase II study evaluating the efficacy of PDS0301 in combination with hepatic artery infusion pump (HAIP) and systemic therapy for patients with metastatic colorectal cancer or intrahepatic cholangiocarcinoma.First Author: Jonathan Matthew Hernandez, National Cancer Institute, Bethesda, MD Background: Treatment of advanced liver tumors continues to pose significant challenges.Despite advances in immunotherapies, including immune checkpoint blockade, responses in colorectal liver metastases and biliary tract cancers remain suboptimal.The lack of robust clinical efficacy is likely myriad, including immunosuppression by the tumor microenvironment and poor susceptibility of these tumors to immune infiltration Gemcitabine and Oxaliplatin) for ICC will be introduced.Patients will be evaluated for response at eight-week intervals.The primary endpoint is overall response rates to PDS0301 and HAIP/systemic combination therapy.Secondary objectives include hepatic progression-free survival (PFS), extra-hepatic PFS, overall survival, and safety.Scientific objectives include determination of microenvironment alterations through pre-and post-treatment biopsies as well as evaluation of peripheral immune subsets and cytokines.To date, we have enrolled 8 of 23 patients in Cohort 1. Clinical trial information: NCT05286814.Research Sponsor: None.NABNEC: A randomised phase II study of nab-paclitaxel in combination with carboplatin as first line treatment of gastrointestinal neuroendocrine carcinomas (GI-NECs). First Author: Lorraine A. Chantrill, Wollongong Hospital, NSW, Wollongong NSW, NSW, Australia Background: Neuroendocrine carcinomas (NEC) are rare and aggressive cancers. There are no randomised trials to date to establish standard therapy for advanced G3 gastrointestinal (GI) NENs. Extrapolating from small cell lung cancer data, standard practice is to treat G3 GI-NENs with etoposide and carboplatin. Paclitaxel is also active in NECs however there is no data on the role of nab-paclitaxel. NABNEC (ANZCTR # 12616000958482) aimed to determine the activity, safety and tolerability of carboplatin and nab-paclitaxel in advanced G3 GI-NENs and to enhance our understanding of the biology and imaging characteristics of such NENs. Methods: NABNEC was designed as a randomised non-comparative phase II study, evaluating the activity of nab-paclitaxel in patients with advanced and/or metastatic non-resectable G3 GI-NENs. The statistical plan was that 46 evaluable patients in the experimental arm would give 80% power and 95% confidence to rule out a 30% RR in favour of a more interesting RR of 50% at 6 months. Protocol version 3.0 was amended and randomisation to the control arm was suspended after 12 patients. Primary endpoint was objective response rate (RR) by RECIST 1.1. Secondary endpoints were progression free survival, overall survival, adverse events by NCI-CTCAE V4.03 and quality of life (EORTC QLQC30, QLQ-GINET21 questionnaires). Translational research endpoints include blood and tissue biomarkers including circulating tumour cells profiling, mutation profile (whole exome sequencing) and DNA methylation profile correlated with clinical endpoints. Correlation of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) to early response has also been evaluated. Results: 60 patients were accrued between Sep 2016 and Dec 2021 from 16 centres, resulting in 58 evaluable patients, 12 (control arm), 46 (experimental arm). 43 patients (75%) had tumours with Ki-67.55%; the remainder had Ki-67 between 20 and 55%. About 20% had pancreatic primaries; more than half had liver metastases. The NABNEC trial met its primary endpoint. RR was 53% (38-69%) in the experimental treatment arm compared to 42% (16-71%) in the control group. Progression free survival was not different between the 2 treatments. 24m overall survival was 25% in the experimental group compared to 17% in the control. Grade 3 toxicity was worse in the nab-paclitaxel arms (52% v 42%). Quality of life and tertiary outcomes are being analysed. Conclusions: The combination of carboplatin and nab-paclitaxel is an active regimen for G3 GI-NENs. Further evaluation in a Phase III study is warranted. Clinical trial information: ACTRN12616000958482. Research Sponsor: National Health and Medical Research Council (NHMRC). To our knowledge, this is the first of its kind analysis describing the safety and effectiveness of repeat PRRT in a US cohort. We show that repeat PRRT may benefit select patients and has an acceptable safety profile. Larger prospective clinical studies are required to identify patient groups that are more likely to benefit from repeat PRRT. Research Sponsor: None. The incidence and prevalence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are increasing worldwide. Surgery remains the only curative modality. Because of limited data on patterns of recurrence, real-world surveillance practices and duration vary widely. In 2018, the Commonwealth Neuroendocrine Tumour Research Collaboration (CommNETs) published consensus surveillance guidelines for patients with completely resected GEP-NETs. Our aim was to assess adherence to the CommNETs guidelines for surveillance practices for this patient population at our center. Methods: We conducted a retrospective cohort study of patients with GEP-NETs seen for a new patient appointment at Princess Margaret Cancer Centre (PMCC) from 2019-2022. Patients were included if they had a completely resected GEP-NET and followed on surveillance at our center. Demographic and tumor characteristics, surveillance practices, and clinical outcomes were abstracted. Summary statistics and a descriptive comparison of surveillance practices were completed. Results: Out of the 374 new patient appointments, 87 met the inclusion criteria.

Visit meetings.asco.org and search by abstract for the full list of abstract authors and their disclosure information. of cancer testis antigen expression with high type-I interferon signal and prognosis in small bowel neuroendocrine tumors. First Author: Reed I. Ayabe, The University of Texas MD Anderson Cancer Center, Houston, TX Background: Patients with small bowel neuroendocrine tumors (SBNET) frequently present with metastatic disease, and efficacy of available therapies, including immune checkpoint inhibitors (ICI), is limited. Toward developing novel immunomodulatory strategies, we evaluated the tumor immune microenvironment of SBNETs using bulk transcriptional and digital spatial profiling (DSP). Methods: Patients with SBNET who underwent surgical resection at MD Anderson Cancer Center from 2003-2016 were retrospectively analyzed. Overall survival (OS) was assessed using the Kaplan-Meier method and Cox proportional hazards model was used for multivariate analysis (MVA). High expression of CTA and type-I IFN in resected SBNET is associated with longer survival, agnostic of stage or grade. While CTA expression has been implicated in tumor immunogenicity, this is the first work to identify a clinical signal in SBNET. Increased IFN in CTA-high tumors, corroborated by increased stromal NK cell activation, suggests an immune-mediated component of improved survival. Spatial transcriptomic analysis reveals epigenetic differences in CTAhigh tumors and highlights the potential for combination epigenetic modifiers and immunotherapy in future trials. Research Sponsor: None.

Elevated serum VEGFa levels at 8-weeks post treatment correlated with lower PFS.Serum VEGFa level is a potential indicator of effector T-cell suppression, as evidenced by low number of activated cytotoxic T-cells in patients with higher VEGFa levels at baseline.Higher baseline regulatory T-cells were associated with a greater increase in serum LAG-3 levels, suggesting that serum LAG-3 may be an indicator of an immunosuppressive tumor microenvironment.Research Sponsor: None.Risk of second cancers in long term survivors of neuroendocrine tumors of the large intestine.First Author: Callie Fort, BSW Health, Round Rock, TX Background: There is an increasing incidence of neuroendocrine tumors (NET) of the colon and rectum likely related to increased screening colonoscopy and availability of better diagnostics.Most of these tumors identified during screening are low grade earlystage tumors with high cure rates.Data on long term risk of recurrence of NET and other second cancers is lacking.We studied the incidence rates of all second malignancies in survivors of NET of the colon and rectum.Methods: We analyzed data from the Surveillance, Epidemiology and End Results (SEER), Research Data 17Registries, Nov 2022 Sub (2000-2022)to determine the risk of second malignancies in patients with an initial cancer diagnosis of NET of the colon and rectum.With these criteria we had overall 17,907 patients and 157,720 patient years of follow up.The relative risk of subsequent malignancies is reported as a standardized incidence ratio (observed incidence [O]/expected incidence [E] ).Incidence ratios are analyzed over time from initial diagnosis to assess long term risk.Results: Survivors of NET of the large intestine are at Survivors of NET of the large intestine are at risk of developing subsequent malignancies.The information presented may help physicians in effectively monitoring survivors for second cancers at various timeframes from their initial diagnosis.Research Sponsor: None.Phase 2 study of nab-sirolimus in patients with well-differentiated and advanced/metastatic neuroendocrine tumors of the gastrointestinal tract, lung, or pancreas. First Author: Michael J. Demeure, Hoag Memorial Hospital Presbyterian, Translational Genomics Research Institute, Newport Beach, CA Background: Neuroendocrine tumors (NETs; ~2% of all malignancies) commonly arise from the gastrointestinal (GI) tract, pancreas, and lung, often presenting as metastatic disease. The PI3K/Akt/mTOR pathway is implicated in the pathogenesis and progression of NETs. Everolimus, an oral mTOR inhibitor (mTORi), is an option for treatment of NETs of the GI tract, lung, or pancreas but response rates observed in the RADIANT -3 and -4 studies were modest at 4-10%. nab-Sirolimus is a mTORi that utilizes nanoparticle technology to preferentially target tumors and is approved in the USA for malignant perivascular epithelioid cell tumor. In preclinical animal models, nab-sirolimus demonstrated higher intratumoral drug accumulation, improved target suppression, and stronger antitumor activity relative to equal weekly doses of sirolimus and everolimus, warranting further exploration of nab-sirolimus. This study will evaluate efficacy/safety of nab-sirolimus in patients with advanced/metastatic NETs. Methods: This phase 2, multicenter, open-label, single-arm study (NCT05997056) will enroll approximately 21 adults ($18 years) with functional or non-functional, well-differentiated, locally advanced unresectable or metastatic NETs of the GI tract, lung, or pancreas who have received #2 prior lines of therapy, excluding somatostatin analogs (SSTa).Patients with functional NETS are eligible if they have been on a stable dose of SSTa for $12 weeks and had disease progression during SSTa treatment. Eligible patients must have $1 measurable target lesion (per Response Evaluation Criteria in Solid Tumors [RECIST] v1.1), Eastern Cooperative Oncology Group performance status score 0 or 1, and adequate organ function/hematologic parameters.They are not permitted to have received prior mTORi, including nab-sirolimus, or to have tumors with known inactivating TSC1 or TSC2 alterations. Patients will receive nab-sirolimus 100 mg/m 2 by intravenous infusion on days 1 and 8 of 21-day cycles. Treatment will continue until disease progression or unacceptable toxicity, or until discontinuation based on investigator or patient discretion.The primary endpoint is investigator-assessed objective response rate per RECIST v1.1. Secondary endpoints include duration of response, disease control rate, time to response, progression-free survival, overall survival, and safety. Exploratory endpoints include correlation of baseline molecular biomarkers with clinical outcomes. Analysis of study objectives will be descriptive. Study site activation is underway with the first patient on study anticipated for the 3 rd quarter of 2023. Clinical trial information: NCT05997056. Research Sponsor: Aadi Biosciences, Inc.

The primary objective is to estimate the response rate by RECIST 1.1.Secondary objectives include estimation of disease-control rate, duration or response, progressionfree survival, overall survival, and safety signals.The NEC expansion cohort will seek to enroll 10 patients.If at least one objective response is observed, and safety is confirmed, the regimen will be considered for future study.Clinical trial information: NCT03647163.Research Sponsor: None.Preliminary activity and safety results of KRAS G12C inhibitor glecirasib (JAB-21822) in patients with pancreatic cancer and other solid tumors.First Author: Jian Li, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, HaiDian District, Beijing, China Background: KRAS G12C mutation is an oncogenic driver and a validated therapeutic target in solid tumors.Glecirasib, a highly selective, covalent oral KRAS G12C inhibitor, has demonstrated promising clinical activity in NSCLC and CRC; however, the efficacy and safety of glecirasib are unknown in PDAC and other solid tumors with KRAS G12C mutation.Methods: Two phase 1/2 trials (NCT05009329 in China; NCT05002270 in US, Europe and Israel) are evaluating the safety and efficacy of glecirasib in patients (pts) with solid tumor harboring KRAS G12C mutations.As both trials have similar inclusion and exclusion criteria, we have pooled the data from them to assess the effect of glecirasib monotherapy in various types of solid tumor with low incidence of KRAS G12C mutation.Treatment duration after randomization was similar in both arms (3.25 vs. 3.02 months).Fewer patients receiving alternating treatment cycles dropped out of the study due to adverse events compared to patients treated with continuous Gem/nab-Pac (14.9% vs 27.5%).In return, these patients terminated the study slightly more often due to progression of disease (48.3% vs 42.5%).Conclusions: The ALPACA trial suggests that a dose-reduced regimen with alternating cycles of Gem/nab-Pac and Gem monotherapy after 3 induction cycles of standard Gem/nab-Pac is feasible and associated with an OS comparable to standard treatment while resulting in improved tolerability.Clinical trial information: NCT02564146.Research Sponsor: None.Only few randomized clinical trials have been conducted for second line therapy in advanced pancreatic cancer (APC).In these studies, elderly patients are poorly represented, even if the median age at diagnosis of APC is increasing; therefore, limited efficacy and safety data are available.Here, we present a retrospective monocentric analysis of second line chemotherapy in elderly patients treated at our Hospital.Methods:This study included patients with APC and aged.70 years old receiving a second-line chemotherapy for APC at our institution from March 2015 to August 2020.The primary endpoints were progression-free survival to second line (PFS2) and overall survival (OS); the secondary endpoint was safety.The Kaplan-Meier method was used to estimate efficacy outcome; log-rank test and Cox-regression model were used to compare the differences, considering a statistically significant p value , 0.05.Number of metastatic sites and ECOG PS were both also associated with mOS.No unexpected adverse events were reported, and no patients had to interrupt treatment due to toxicity.Conclusions: In our experience, only about a third of elderly pts with APC received second-line therapy; in these patients, ECOG PS, disease's burden and the response to therapy are all positive prognostic factors.With regard to the safety profile, older age does not seem to negatively increase serious toxicities.In conclusion, elderly pts should not be precluded from an active treatment (also in later lines setting) and careful patients selection should guide treatment indication.Research Sponsor: None.Socioeconomic variables in the National Cancer Database: Utilization and impact of income and education in survival models for patients with resected pancreas cancer. First Author: Qianyun Luo, University of Minnesota Medical School, Minneapolis, MN

Pearson and Spearman correlation was assessed.Overall survival (OS) was calculated using Kaplan Meier method.The effects of income and education was calculated using Cox proportional Hazard (PH) models.Results: 69,362 patients met inclusion criteria.Median age was 66 (IQR 59-73), with 48.9% female.The correlation coefficient between income and education based on the 2020 American Community Survey data was 0.48 (p,0.01).Median OS from the time of diagnosis was 21 months.The 5-year OS was 19.4 and 22.7 months for groups with lowest and highest education (p,0.01).Group with missing education has a 5-year OS of 22.4 month, comparable to the group with highest education (p=0.82).The 5-year OS based on income quartiles was 18.7 and 22.5 months for the Q1 and Q4 (p,0.01).Group with missing income has a 5-year OS of 22.4 month, similar to the highest income group (p=0.85).When including combinations of income, education and their interaction, the concordance of Cox models was changed by less than 0.002.Conclusions: For patients who underwent definitive surgery for PDAC, the income and education variables are only mildly correlated, and their inclusion do not have significant impact on OS models.Investigators should reconsider the utility of the aggregate NCDB measures, as they many not fully elucidate income and education disparities and impact on survival.Research Sponsor: None.Demographics and PH model for patients undergoing definitive surgery for PDAC in the NCDB.

Factors associated with increased survival outcomes include insurance status, positive regional lymph nodes, grade/differentiation, treatment facility type and surgical intervention.These findings make a valuable contribution to the ongoing research on disparities affecting survival in patients with pancreatic signet cell carcinoma.Research Sponsor: None.).When stratified by production of CA 19-9, there was no significant difference between rate of MPR between Black and White patients.In the PanCAN KYT analysis, CAnonproduc had higher rates of SWI/SNF alterations (50.0% of CAnonprod vs 30.1% of CAprod, P,0.01;P-adj=ns; ARID1B was the most frequently mutated SWI/SNF gene in CAnonprod (31.0%vs 9.0% CApos, p,0.01;P-adj=ns).Conclusions: CAnonprod were more likely to be Black and have significantly worse rates of MPR following neoadjuvant chemotherapy in patients with localized PDAC.Moreover, CAnonprod was associated with higher rates of SWI/SNF alterations, noting a potential biologic basis for racial differences in chemotherapy response to curative-intent treatment for PDAC.Research Sponsor: None.Almost 30% of gastrointestinal cancers (GI) are diagnosed at an advanced stage.These patients have a poor prognosis with no curative options. Certain demographic and social factors adversely impact health outcomes. However, these have not been well studied in the context of late diagnosis of GI cancers. Methods: Texas and California cancer registries, merged with CDC's Social Vulnerability Index (SVI) database, were used to identify patients diagnosed with gastric, colorectal, pancreatic and liver cancer from 2004 to 2019. To determine the association of demographic and 16 social vulnerability factors, while accounting for differences in tumor characteristics, univariate and multivariate logistic regression analysis (MVA) was performed for each cancer separately. Results: In total, 589,405 patients were included. Of these 166,910 (28.3%) patients had metastasis at diagnosis. This included 55%, 39%, 21%, and 17% of all pancreatic, gastric, colorectal and liver cancers respectively. On MVA, odds of metastatic cancer at presentation decreased with increasing age (except for pancreatic cancer where odds increased). Across all 4 cancer types, females and Asians had decreased odds while Blacks, uninsured and patients on Medicaid had increased odds of metastatic cancer at diagnosis. Poverty below 150% increased odds of metastatic pancreas, liver, and colorectal cancers at diagnosis. Odds were decreased for households with adults aged over 65 years for pancreas, colorectal and gastric cancers. Conclusions: This study has identified multiple demographic and social factors associated with odds of having metastatic GI cancer at diagnosis. Interventions aimed towards these at-risk populations offer an opportunity for early diagnosis and improved survival. Research Sponsor: None.

.024) and higher rate of acute pancreatitis (p 0.037) in pancreatic cancer. On multivariate analysis, race was not associated with difference in recurrence free survival (12 months in AA vs. 14 months in NHW; p 0.96) when adjusted for age, sex, alcohol use, tobacco use, cancer stage and chemotherapy. High mean age, clinical stage II, III and IV, current alcohol use, underweight and BMI.30 and cerebrovascular accident as a comorbidity was associated with worse overall survival when adjusted for other variables. Conclusions: Our study revealed that pancreatic cancer in AA was diagnosed at a younger age, associated with active smoking and pancreatitis. We observe there was no difference in treatment initiation among AA and NHW. There was no significant difference in recurrence free survival and overall survival compared to NHW when adjusted for other variables. Future studies incorporating germline mutations, novel biomarkers are needed to determine impact of racial health disparities on outcomes in pancreatic cancer. Research Sponsor: None.

Wholomics was also capable of differentiating between early stage (stages I and II) and late-stage (stages III and IV) pancreatic cancer with an accuracy of 100%.Conclusions: Taken together, this study demonstrates that diseasespecific molecular signatures in peripheral blood can distinguish patients with PDAC from healthy individuals and patients with pancreatitis with very high accuracy.If validated in additional cohorts, this method could be evaluated as a screening test for PDAC to allow for early detection and improve patient outcomes.Research Sponsor: Wholomics GmbH.The radiological morphology of mesopancreas: A new variable to predict a positive vascular margin after pancreatoduodenectomy for pancreatic ductal adenocarcinoma?First Author: Julie Navez, Hopital Erasme, Hôpital Universitaire de Bruxelles, Bruxelles, Belgium Background: The most frequently invaded surgical margins on pancreatoduodenectomy (PD) specimens of pancreatic ductal adenocarcinoma (PDAC) are vascular margins, especially the superior mesenteric artery (SMA), also called mesopancreatic margin.Considering embryology, it may be hypothesized that PDAC cells tend to infiltrate the retroperitoneum through the contents of mesopancreas, justifying the frequent SMA positive margin.Because the radiological aspect of mesopancreas has been poorly studied, the aim of this original research was to assess the mesopancreatic infiltration on diagnostic imaging, corroborate with the corresponding margin pathology and evaluate the impact on survival in PDAC patients who underwent PD.Methods: From 2015 to 2021, all patients who underwent PD for PDAC with curative intent were reviewed, excluding patients lost to follow-up, who died postoperatively or within the first year for nononcological reason, and those with unavailable preoperative imaging. Surgical margins of pathological specimens were reassessed.Blinded reviewing of preoperative radiographic images was conducted.According to qualitative assessment, the mesopancreas tissue was defined as normal fat (NF), fat stranding (FS) or solid infiltration (SI).Results: 133 patients were included in the study, including 51 (38%) who received neoadjuvant therapy.The tumor location was into the head or the uncinate process in 54% and 46%, respectively.At diagnosis, PDAC were classified as resectable (51%), borderline resectable (28%) and locally advanced (9%) according to the NCCN classification.FS or SI in the mesopancreas was present in 45 (34%) and 18 (14%) patients, respectively.Tumor size on imaging, tumor location, chronic obstructive pancreatitis, vascular contacts and NCCN resectability status were predictive factors of mesopancreas infiltration (p,0.001).Median overall and disease-free survivals were significantly lower in case of SI compared to NF and FS in the mesopancreas.When comparing patients with mesopancreatic FS at diagnosis who received neoadjuvant therapy (n=20) to those who underwent upfront surgery (n=25), no significant impact was observed in survivals.R0 resection was obtained in 36%; in all patients with R1 resection, a vascular margin was involved.Tumor size at pathology, SMA margin and resection status were factors that were significantly influenced by the radiological infiltration of the mesopancreas.Conclusions:The SI of mesopancreas on diagnostic imaging was associated with a poor prognosis, but not FS, in patients who underwent PD for PDAC.SMA margin and resection status were correlated with the radiological texture of the mesopancreas, which suggests to further explore underlying mechanisms related to tumoral invasion of vascular margin and mesopancreas. Research Sponsor: Fonds Erasme.First Author: Ashish Manne, The Ohio State University Comprehensive Cancer Center, Columbus, OH Background: Pancreatic ductal adenocarcinoma (PDA) is one of the deadliest cancers with poor outcomes.Around 20% arise from premalignant lesions (PML) including IPMN.Current guidelines recommend risk stratifying IPMN based on the location, size, and imaging characteristics after first diagnosis, followed by endoscopic ultrasound (EUS) in high-risk populations, and annual or bi-annual imaging.This approach can be improved with cfDNA testing.Traditional mutation testing in cfDNA is not useful secondary to their poor prevalence/detection rates.We propose ep-Sig to improve surveillance and early detection of PDA transformation.Methods: We curated an 11-gene cfDNA ep-Sig from the literature with a proven role in the malignant transformation of IPMN.Evidence suggests that epigenetic changes in every gene of this panel have a role in carcinogenesis in IPMNs.We compared RNA and gene expression of the genes in this ep-Sig between normal (NT) and PDA tissues using a web-based tool, TNMplot.com that uses the data from the Gene Expression Omnibus of the National Center for Biotechnology Information (NCBI-GEO) or Cancer Genome Atlas (TCGA), Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and The Genotype-Tissue Expression (GTEx) repositories was used create this tool.It uses Mann-Whitney or Kruskal-Wallis tests to compute statistical significance.We used cell-free epigenome atlas (CFEA) database to examine the prevalence of these markers in cfDNA of PDA patients.Results: RNA expression of all the genes from the ep-Sig combined was significantly lower in PDA than NT (0.45, p=3.13e-26).Gene expression was 8/11 genes was lower in PDA tissues thanNT (0.44,. The other 2 genes were not detected in the tested samples. Prevalence of all the markers in ep-Sig was . 90%. Conclusions: Our proposed ep-Sig has a high prevalence in PDA patients and has reliable preliminary evidence in tissues suggesting its diagnostic value. This study is the first step in developing non-invasive cfDNA testing with the potential to improve the current surveillance strategies for IPMN pending larger prospective studies. Research Sponsor: None.

Clinical impact of KRAS mutations in metastatic pancreatic ductal adenocarcinoma (PDAC).First Author: Carter Norton, Huntsman Cancer Institute, University of Utah Health, Salt Lake City, UT Background: Mutations in the KRAS oncogene occur in most PDAC and lead to the activation of the KRAS protein.Little is known about the differential impact of KRAS mutations on the outcomes of patients receiving standard of care cytotoxic treatments for metastatic disease.KRAS inhibitors are emerging as promising options for this disease and understanding the impact of distinct KRAS mutations in patient outcomes is needed.Methods:This study used the nationwide Flatiron Health electronic health record (EHR)derived de-identified database from 5,369 patients.Adult patients with diagnosis of metastatic PDAC who received at least one line of systemic therapy and had sufficient data available were included in this analysis.Median time to next treatment (TTNT) and overall survival (OS) time were calculated for three common first-line treatments and KRAS mutations.TTNT and OS were calculated for each permutation of treatment and each KRAS mutation.Hazard ratios (HR) were generated for each KRAS mutation and treatment, accounting for potentially confounding variables.Results: Of the 5,369 patients, 2,472 met the inclusion/exclusion criteria.G12C had the shortest median OS (7.5 mo) and G12R had the longest (9.1 mo).Overall, KRAS mutation-positive patients had a median OS of 8.6 mo, compared to 11.7 mo for KRAS Wild Type (WT) patients.A Cox Proportional Hazard analysis of OS across KRAS mutation status found that G12C, G12V, G12D, and Other Non G12/13 KRAS had significantly higher HR than KRAS WT.A comparison of the three common firstline interventions for metastatic PDAC showed that FOLFIRINOX had the longest median TTNT (5.3 mo) and the longest OS (10.2 mo), while Gemcitabine had the shortest TTNT (2.6 mo) and OS (5.9 mo).A Cox Proportional Hazard analysis of OS across all patients found that Gemcitabine and Gemcitabine with Nabpaclitaxel had significantly higher HR than FOL-FIRINOX.FOLFIRINOX had the longest TTNT in the G12C, G12V, G12D, G12R, and other non-G12/G13 KRAS groups (see table). Conclusions: Our data suggest that FOLFIRINOX has a longer TTNT than other first-line regimens for KRAS G12C, G12V, G12D, and G12R. KRAS G12C was associated with the shortest OS among common KRAS mutations. Research Sponsor: None. Pancreatic ductal adenocarcinoma (PDAC) remains an immense challenge within oncology, with only 15-20% of cases initially qualifying as resectable. Based on National Cancer Database analyses there is an increase in neoadjuvant chemotherapy (NACT) use, with potential downstaging effects. Yet, a subset of neoadjuvant-treated patients fail to proceed with curativeintent surgery, leading to worse outcomes. This retrospective analysis aims to uncover factors that predict NACT use and the impact on survival outcomes. Methods: A cohort of 543 consecutive non-metastatic PDAC patients treated at an NCCN-designated comprehensive cancer center between 2015 and 2022 were prospectively enrolled into a REDCap database. Based on NCCN resectability criteria, initial CT staging placed 96 patients as upfront resectable. Survival outcomes were compared using univariate and multivariate cox regression analyses. These findings underscore the need for more robust selection criteria in resectable PDAC patients to undergo NACT. Leveraging real-world data helps identify predictive factors of treatment decision making and their impact on patient survival outcomes. Research Sponsor: 1440 Foundation for the Canopy Cancer Collective Learning Health Network. Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and is projected to be the 3 rd leading cause of cancer related death in the United States in 2023. Most patients are diagnosed at an advanced/metastatic stage and 5-year survival remains dismal at ~12%. While effective regimens are limited, some patients benefit significantly from chemotherapy, while others harbor disease that progresses despite treatment. Unfortunately, it is impossible to predict individual patient outcomes on treatment such that only general prognostic information can be provided to patients and families. Quantification of circulating tumor DNA (ctDNA) is a promising prognostic biomarker and emerging evidence shows that baseline ctDNA tumor fraction (TF) is prognostic in several tumor types. This study represents the largest data set reported to date aimed at evaluating the prognostic value of ctDNA TF in metastatic PDAC (mPDAC). Methods: This study used a cohort of patients from the de-identified nationwide Flatiron Health-Foundation Medicine pancreatic clinico-genomic database who underwent ctDNA testing using FoundationOne Liquid or FoundationOne Liquid CDx as part of routine care. Data originated from approximately 280 US cancer clinics. Patient/disease characteristics, laboratory and treatment data were captured from the electronic health record. , 0.001). Conclusions: ctDNA TF is a prognostic biomarker in mPDAC with potential to inform expected longevity of patients. Uniform cohorts, with regard to treatments given and line of therapy, would help further evaluate the ability of ctDNA TF to identify patients with aggressive disease and inform the design of future studies to personalize therapeutic decision-making. Research Sponsor: None.

).Visit meetings.asco.organdsearchbyabstractfor the full list of abstract authors and their disclosure information.impactandprognosticrole of systemic inflammatory response index (SIRI) in advanced pancreatic cancer: PANTHEIA-Spanish Society of Medical Oncology (SEOM) study results.First Author: Vilma Pacheco-Barcia, Department of Medical Oncology Hospital Universitario de Torrejón, Madrid, Spain Background: Whilethe systemic inflammatory response assessed by SIRI has been recognized as a prognostic factor in advanced pancreatic cancer, understanding its association with patients' nutritional status may provide deeper insights into disease biology and outcomes.Methods:This is an observational, non-interventional and multicenter study (15 Spanish hospitals) promoted by SEOM, including retrospective and prospectively patients with metastatic pancreatic cancer in routine clinical practice.Clinical and nutritional data was recorded, and SIRI was calculated using the formula: (neutrophils x monocytes) / lymphocytes.We considered SIRI score as low (SIRI-L) or high (SIRI-H) using a cutoff of ,2.3 or $2.3, respectively based in our previous findings.PANDORA-SEOM tool was used for electronic data collection.The main outcome is to correlate SIRI with the nutritional status.Other aims were to correlate the overall survival (OS) and progression-free survival (PFS) with SIRI and weight loss in the 3 months prior to diagnosis using the Kaplan-Meier method and multivariate Cox regression model.Data from the pilot study is presented in this abstract, and more data is expected to be available prior to the Congress.Results: We included 144 patients retrospectively: 65% men, with median age of 66 years (range 45-81).The most common 1 st line chemotherapy regimen were gemcitabine + nab/paclitaxel (63.2%), mFOLFIRINOX (20.1%) andFOLFOX (11.8).Prior to diagnosis, 54.2% of patients had weight loss .5 Kilograms (Kg) and 22.9% lost .10Kg.SIRI-H was significantly associated with weight loss .5Kgcompared to SIRI-L, 35.7 vs 24% respectively (p=0.028).Patients with a pretreatment SIRI-H showed shorter OS compared to SIRI-L (median OS 5 vs 12 months, Hazard Ratio (HR) 3.047, 95% Confidence Interval (CI) 2.069-4.488,p,0.001),aswellas shorter PFS (median PFS 5 vs 10 months, HR 2.364, 95% CI 1.650-3.387,p,0.001).In the patient subgroup that experienced .5Kgweightloss,SIRI-Hwas associated with worse OS (median OS 4 vs 12 months).We didn't find an association between CA19.9 level and SIRI or weight loss.Multivariate analysis identified SIRI as an independent prognostic factor for OS (HR 2.962, 95% CI 1.911-4.591,P,0.001).Conclusions: Our findings underscore the importance of SIRI as a significant predictor of nutritional status and disease aggressiveness in patients with metastatic pancreatic cancer.Prospective data will help us to validate these findings.Research Sponsor: Spanish Society of Medical Oncology (SEOM).In-hospital outcomes of acute pulmonary embolism in patients with gastrointestinal cancer: A nationwide study.First Author: SAJANA POUDEL, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL Background: Cancer is a well-established risk factor for the development of pulmonary embolism (PE), especially the.gastrointestinal (GI) cancers.While multiple studies have reported the burden of PE in cancer patients, recent data comparing in-hospital outcomes among different types of cancer patients are lacking.This study aimed to investigate the clinical and healthcare utilization outcomes of hospitalized patients with acute PE in the context of gastrointestinal (GI) cancers.Methods: A cross-sectional study was conducted using data from the National Inpatient Sample (2016-2020).There was no significant difference in mean length of hospital stays and mean total hospital charges in patients with or without cancer.Similarly, no significant differences were observed in complications such as requirement for mechanical ventilation, arrhythmia, cardiac arrest, need for vasopressor and thrombolysis.Conclusions: In-hospital mortality in patients with acute pulmonary embolism is significantly higher in all types of GI cancer, however; there is no significant differences in hospital length of stay and total hospital charges in patients with or without cancer.Research Sponsor: None.The COVID-19 pandemic increased all-cause mortality and disrupted healthcare delivery in the United States.Interruptions in cancer screening and surveillance because of the pandemic resulted in delayed diagnosis, diagnosis at later stages, and worse cancer-related outcomes.However, the effect of COVID-19 on pancreatic cancer outcomes has not been reported.This study aimed to investigate this question.Methods:We studied consecutive patients with unresectable and metastatic pancreatic cancer treated at the University of Cincinnati Cancer Center.Patients were divided into 2 cohorts: from January 2018 to December 2019 (pre-COVID) and from January of 2020 to December of 2021 (during-COVID).Descriptive data on patient characteristics, ECOG performance status (PS), laboratory values, therapies, and mortality were obtained by pre-and during-COVID.The categorical variables were compared using the Pearson Chi-square test for contingency tables (or Fisher's exact test when the expected frequency within any cell was less than 5 in the contingency table), and the t-test or ANOVA was used for continuous variables.For overall survival time, the Kaplan-Meier curves were compared between pre-and during-COVID using log rank test.We fitted univariable Cox proportional-hazards model for each interest variable, and the multivariable Cox models, which includes only significant variables.Results:There were 81 and 64 patients in the pre-and during-COVID cohorts, respectively.Patients diagnosed during COVID were more likely to be female, have better PS, have higher proportion of alcohol use, and were more likely to receive 5-FU-based (compared with gemcitabine-based) chemotherapy upfront.There was no overall survival difference between the two cohorts.A Cox proportional hazards model showed that PS at diagnosis, history of chronic pancreatitis, any chemotherapy compared to no chemotherapy, serum albumin prior to initial chemotherapy, and body mass index at time of diagnosis were associated with survival.Conclusions: We observed no difference in overall survival in patients diagnosed with advanced stage pancreatic cancer during the first two years of the COVID-19 pandemic compared with the two prior years.While some differences were observed between patient groups and treatment selection before and during the pandemic, a concerted effort to maintain cancer care appears to have minimized the impact of the pandemic.Further analyses on patients undergoing treatment are being conducted.Research Sponsor: None.Pancreatic cancer and diabetes: The effects of race and genes.First Author: Michael Shu, University of Cincinnati College of Medicine, Cincinnati, OH Background: Pancreatic cancer and diabetes mellitus (DM) have been shown to be connected, but the genetic associations between the two have not been well characterized.The goal of this study was to identify racial and genomic patterns that relate the timing of DM onset with a pancreatic cancer diagnosis.Methods: Consecutive pancreatic cancer patients treated at the University of Cincinnati Cancer Center with available tumor genomic profiles were studied.Descriptive statistics for 133 genes, patient characteristics, cancer stage, treatment details, and family history were analyzed.Categorical variables were compared using the Pearson Chi-square test for contingency tables (or Fisher's exact test when the expected frequency within any cell was less than 5 in the contingency table), and the t-test or ANOVA was used for continuous variables.For overall survival, we generated Kaplan-Meier curves by DM diagnosis, and fit univariable Cox Proportional-Hazard models for each interest variable for all patients, and multivariable Cox models, which included only significant variables.Results: Of 147 individuals with pancreatic cancer (median age 67 years, 49% female, 12% Black), 46.3% had a DM diagnosis.Of these, 62% had chronic DM, while 38% were diagnosed within one year of their pancreatic cancer diagnosis.Black individuals were more likely to have DM diagnosed (76.5% vs 41.7%, p = 0.007), and were more likely to have been diagnosed within a year of pancreatic cancer (69.2% vs 30.2%, p = 0.023), compared with White individuals.There were 15 genes found to be upregulated in those with DM and pancreatic cancer, and 11 genes found to be downregulated.RNF43 mutation was more prevalent in pancreatic cancer patients with chronic DM than those without DM (71.4% vs 32.5%, p = 0.048), although absolute number of individuals with the mutation were low.No other genomic association on the timing of DM and pancreatic cancer was found.A SMAD4 mutation was associated with a 121% increased risk of mortality (HR = 2.21, 95% CI 1.16-4.19,p=0.016). Conclusions: In a cohort of pancreatic cancer patients at a single center, Black individuals were more likely to have DM diagnosed closer to pancreatic cancer diagnosis (rather than earlier), compared with other races. No remarkable genomic association was found. This highlights that a diagnosis of diabetes may be related to inequities in healthcare, as opposed to true genomic differences, and needs to be explored in larger datasets. Research Sponsor: None.

Conclusions: De-escalation was common among pts continuing FFX/mFFX treatment, with oxaliplatin the most frequently omitted component in later administrations. Over the 6 weeks following FFX treatment initiation, the actual vs. standard dose was lowest for 5FU, followed by irinotecan, while median leucovorin and oxaliplatin doses were close to standard dose over 3 two-week cycles. The omission of components of the regimen may indicate that mFFX lacks tolerability for many pts. Research Sponsor: Ipsen Biopharmaceuticals, Inc.

IRs of all other AEs were numerically higher for FFX-only pts but differences were not statistically significant.Conclusions: A RW cohort of mPDAC pts receiving FFX-only experienced more AEs per pt-month of 1L and reduced likelihood of proceeding to subsequent lines of therapy compared to pts treated with FFX + GnP.Identifying predictive biomarkers may distinguish FFX non-responders and obviate AEs.Research Sponsor: Ipsen Biopharmaceuticals, Inc.Patterns of surgery and adjuvant therapy in pancreatic carcinoid tumor: An NCDB analysis.First Author: Connor Lanoue, Creighton University School of Medicine, Omaha, NE Background: Pancreatic Carcinoid Tumor (PCT) is a neuroendocrine tumor (NET) of the gastrointestinal (GI) tract composed of Argentaffin cells.Of the primary pancreatic cancers, NETs are exceedingly rare in comparison to pancreatic adenocarcinoma, accounting for less than 2% of pancreatic cancer diagnoses.PCTs constitute for only a subset of these and hold a better prognosis than adenocarcinoma (What Is a Pancreatic Neuroendocrine Tumor?|American Cancer Society, n.d.).GI carcinoid tumors classically originate in the appendix, ileum, or rectum, and are seldom a primary neoplasm of the pancreas.PCTs generate secretory products with Serotonin being the most frequently isolated.Some cases may produce a carcinoid syndrome with characteristic diarrhea, cutaneous flushing, and bronchospasm(Ha & Tan, 2012). Surgical resection is the hallmark of treatment, though other modalities of management are available. Due to the rarity of PCT, no significant study exists in the literature analyzing the association of survival with receipt of surgery or predictors of receipt of surgery. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with PCT from 2004 to 2019 using the histology codes 8240 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, Binary Logistic Regression and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 29 and statistical significance was set at a = 0.05. Results: 2237 patients with PCT formed the final sample, with an average age of 61 years of age. 724 patients (32.After controlling for covariates, receipt of surgery was independently associated with decreased overall mortality (HR=.380; p,0.05). Decreased age, lower grade

Progression free survival (PFS) as well as 3-year overall survival (OS) were assessed using Kaplan-Meier statistics and multivariable Cox regression models (adjusted for age, pN stage, primary tumor location and systemic treatment). Results: In total we identified 1098 cases surgically treated for pancreatic cancer and fulfilling the inclusion criteria. 340 patients had an R0 wide/CRM-resection, 410 patients an R0 narrow/CRM+ resection, and 348 patients an R1 resection. The R0 wide/CRM-status was associated with a significantly increased median 3-year OS rate compared to the other two groups (51,5%, 37,4% and 26,7% for R0 wide/CRM-, R0 narrow/CRM+ and R1, respectively). mPFS was also longer in the R0 wide/CRM-group. These findings were robust with regards to grading. 5-FU based adjuvant treatment was mainly mFOLFIRINOX and show better outcome as compared to gemcitabine-based treatments. Conclusions: The present study was performed using real world data reflecting actual clinical settings. The results obtained are in good agreement with data from clinical trials, including the prognostic role of the R-and N-Status as well as the efficacy of adjuvant chemotherapy protocols used. Research Sponsor: None. Pancreatic ductal adenocarcinoma (PDAC) is associated with poor survival with nearly 80% mortality within the first year after diagnosis. There have been modest incremental improvements in survival over the last decade, however the reason for this improvement is unclear. The aim of this study is to evaluate the trends of diagnosis and survival in the last two decades using large public national databases. Methods: Incidence rates of PDAC between 2001 and 2020 (age-adjusted to the 2000 US standard population) were evaluated in the United States Cancer Statistics (USCS) database, representing approximately 98% of the US population. The data was analyzed with SEER*Stat using Joinpoint regression. A survival analysis was subsequently conducted using the American College of Surgeons' (ACS) National Cancer Database (NCDB), of PDAC cases diagnosed between 2004 and 2015.Survival outcomes were stratified by AJCC stage. Kaplan-Meier survival curves were generated, and log-rank tests were conducted to assess differences in survival between stages. Cox proportional hazards model was employed to estimate hazard ratios and adjust for potential confounders. The analysis was performed with IBM SPSS 24.

Prognosis and clinical and molecular characteristics of patients with brain metastasis secondary to pancreatic ductal adenocarcinoma.First Author: Mahmoud M.G.Yousef, The University of Texas MD Anderson Cancer Center, Houston, TX Background: Pancreatic ductal adenocarcinoma (PDAC) is a disease of poor prognosis, while secondary brain metastasis (Br-M) is reported to occur in less than 1% of patients with PDAC, with only limited data available suggesting that patients with Br-M have even worse prognosis.We sought to evaluate the prognosis, clinical, and molecular characters of patients with Br-M secondary to PDAC.Methods: The Foundry software platform was used to retrospectively query the electronic health records to identify patients diagnosed with Br-M secondary to PDAC from 2005 to 2023; clinical, molecular, and oncologic outcome data were collected.Results: Br-M was diagnosed in 44 patients with PDAC.This is the largest cohort for patients with Br-M form PDAC reporting thatsecondary Br-M is a late complication, associated with extremely poor prognosis, in patients who received multiple lines of therapy and have widely metastatic disease.The frontal lobe is the most frequently affected site.KRAS was the most frequently detected mutation and G12V subtype was more prevalent.surgicalresectionfor Br-M was associated with better OS.Research Sponsor: National Cancer Institute; the Cancer Prevention & Research Institute of Texas; ASCO.Frequency and oncologic outcomes of KRAS mutations in circulating tumor DNA of patients with pancreatic ductal adenocarcinoma.First Author: Mahmoud M.G.Yousef, The University of Texas MD Anderson Cancer Center, Houston, TX Background: KRAS genetic alterations have been reported in more than 90% of pancreatic ductal adenocarcinoma (PDAC).The association of KRAS mutation subtypes detected in circulating tumor DNA (ct-DNA) with survival remains unclear.We investigated the rate of liquid biopsy detected KRAS mutation subtypes, and their association with overall survival (OS) in patients with PDAC.Methods: The Foundry software platform was used to retrospectively query a single-institution Electronic Health Records to identify patients with PDAC who underwent ct-DNA liquid biopsy from 2018 to 2023 and extract their oncologic outcomes.Detection of KRAS mutation in liquid biopsies of patients with metastatic PDAC is associated with worse OS.KRAS G12D/Q61 alterations detection is associated with worse OS compared to other KRAS mutation subtypes.Ct-DNA detection of co-occurring CDKN2A mutation is associated with worse OS in patients with KRAS positive metastatic disease.Research Sponsor: National Cancer Institute; the Cancer Prevention & Research Institute of Texas; ASCO.Literature describing associations between patient body mass index (BMI) and survival in pancreatic ductal adenocarcinoma (PDA) remains inconsistent.This heterogeneity may be due to studies using pre-diagnosis BMI and including few metastatic patients despite high prevalence at diagnosis.Furthermore, BMI may not adequately reflect other body compositions such as those reflected via morphomic variables (subcutaneous fat, visceral fat, muscle, and fascia) that may have unique associations with survival.In this study, we sought to explore the relationships between detailed body composition in patients with metastatic PDA on both overall survival (OS) and progression-free survival (PFS).Methods: We evaluated data and scans from a phase 3 clinical trial in which 528 patients with metastatic PDA with no prior chemotherapy were randomized to either FOLFIRINOX or modified FOLFIRINOX plus devimistat.No differences in response rate, median PFS or OS were observed.Of the 528 enrolled patients, 377 had baseline CT scans eligible for morphomic evaluation for which Analytic Morphomics was used to measure body composition.For analysis, morphomic variables were summed across the T10-T12 and L1-L4 vertebrae and then divided into tertiles.BMI at diagnosis was evaluated in tertiles and per WHO standards.Cox proportional hazards models and cubic splines were used to evaluate associations between BMI, morphomic variables and PFS, OS.Univariate and multivariate models were evaluated.Germline testing in patients with early-onset pancreatic cancer (EOPC).First Author: Hamid Ehsan, Atrium Health Levine Cancer Institute, Charlotte, NC Background: EOPC, defined as pancreatic cancer (PC) diagnosed at 60 years of age or younger, is associated with significant life years lost.Approximately 5-10% of averageonset PC have an underlying germline etiology.Currently NCCN & ASCO guidelines recommend germline testing in all pts w PC.However, there is limited data regarding to what extent pts with EOPC pursue recommended germline testing.We examined the findings from genetic evaluation in EOPC.Methods: A retrospective review of EOPC pts at the Levine Cancer Institute who underwent clinical genetic assessment between January 2019 and December 2021 was performed.Data on clinicodemographic, family history, and genetic testing results were obtained and analyzed descriptively.Among the 10 pts with PVs, only two reported any first or second-degree family members with cancer.Conclusions: In this cohort of EOPC at a large community multi-site cancer center, 16% of patients had germline PVs, higher than reported in older patients with PC.Only 20% of pts w PVs reported first or second-degree family members with cancer and highlights the importance to recommend germline testing independent of family history even among EOPC cohorts.Further investigation to clarify reasons for refusal of germline testing in EOPC should be evaluated.Research Sponsor: None.Survival of patients with microsatellite instability-high and Lynch syndrome-associated pancreatic ductal adenocarcinomas. First Author: Naaz Nasar, Memorial Sloan Kettering Cancer Center, New York, NY Background: Pancreatic ductal adenocarcinoma (PDAC) remains a challenging disease due to its aggressive nature, late-stage diagnosis, and limited treatment options. There is an increased interest in cancers which harbor microsatellite instability (MSI) due to their susceptibility to immune checkpoint inhibitors. MSI in PDAC is rare, and little is known about survival in this subtype of pancreas cancers. Our aim was to assess overall survival in surgically resected high microsatellite instability (MSI-H), mismatch repair deficient (MMRd), and Lynch Syndrome (LS) associated PDACs treated in our center. Methods: Patients with surgically resected PDACs from 1990 to 2023 were identified. A total of 936 cases were sequenced utilizing MSK-IMPACT, a targeted next generation sequencing platform. Patients with germline or sporadic pathogenic variants or likely pathogenic variants in one of the DNA MMR genes MLH1, MSH2, MSH6, PMS2, or 3' end of EpCAM were identified. MSI-H, MMRd, and LS-associated cases were matched to patients with microsatellite stable or MMR proficient, non-LS-associated PDAC in a 1:2 ratio with a direct match on age (65 years), gender, and year of surgery (63 years). Kaplan-Meier curves were used to visualize the data. A generalized estimating equation (GEE) cox model with robust sandwich estimator was used to compare matched cohorts. Results: 17 patients with MSI-H, MMRd or LS-associated surgically resected PDACs were identified. Five patients were classified as MSI-H, 3 patients were MSIindeterminate, and 9 patients were microsatellite stable. Eight patients were found to have pathogenic germline variants in LS-associated genes. The remaining nine patients had sporadic pathogenic DNA MMR gene variants (MLH1 n=3, MSH6 n=6). Median age at surgery was 66 (interquartile range (IQR) 60-77), 41% of the patients were female, and median year of surgery was 2014. MSI-H, MMRd or LS-associated PDACs were matched to 34 control patients. The median survival time of the cases was 12 years vs. 1.9 years in the control group. Five-year survival rate was 81% (IQR 60-100%) and 18% (7.4%-43%), respectively. LS-associated, MSI-H or MMRd status in resectable PDAC was a strong predictor of good prognosis (hazard ratio 0.17, 95% CI 0.07-0.38, p value ,0.001). Conclusions: MSI-H, MMRd or LS-associated PDACs displayed significantly better survival compared to their MSI-stable, MMR proficient, non-LSassociated counterparts, in the era before routine use of immunotherapy. It is expected that survival will be increased further with more frequent availability of immunotherapy. Research Sponsor: None.

First Author: Connor Hannon, The Ohio State University Comprehensive Cancer Center, Columbus, OH Background: A one-day multi-disciplinary clinic allows for a comprehensive evaluation of patients in a single-visit format. This study aims to evaluate the impact of a one-day pancreatic cancer multi-disciplinary clinic (PMDC) on patient-centric outcomes. Methods: Patients with pancreatic cancer who were seen at The Ohio State University PMDC from January 2021 to March 2023 were identified. Patient-centric outcomes were evaluated including time from diagnosis to first evaluation and treatment, number of supportive care referrals completed, and number of physical trips to the medical center leading up to the first treatment. Outcomes were compared to pancreatic cancer patients seen in the year prior to the opening of the PMDC (non-PMDC). Pancreas cancer (PC) is the third leading cause of cancer death in the United States. Canopy Cancer Collective (CCC) was founded in 2019 given the urgent need for improvements in survival and patient experience. Through interdisciplinary teams inclusive of patients, 14 care centers formed a learning health network (LHN) to share data and best practices to accelerate improvements in PC care delivery and outcomes. Methods: In October 2022, LHN representatives gathered to establish aims for the year.

Median follow up was 31.1 months (2.0 -73.2).Among the evaluable patients, 63% were male, median age at diagnosis was 73 years (63 -84), pre-treatment CA 19-9 149.5 U/mL (2.0 -19358.0).The majority of patients had cT2-3 (94%) and cN0 (87.5%) disease.In patients who underwent resection, median time from radiation to surgery was 19.7 days (14.8 -42.4), with median of 18 lymph nodes removed(11 -27).Pathologically involved nodes were present in 69.2% of patients with a median of 2 nodes (1 -10).Five patients (31.3%) received neoadjuvant chemotherapy, and ten (62.5%) received adjuvant chemotherapy.At the time of data cutoff, median overall survival was 31.1 months (2.3 -73.6), and median locoregional control and distant metastasis free survivals were 32.8 months (4.0 -59.5) and 15.3 months (0.4 -73.6), respectively.No further radiation related toxicities were noted since the prior report.Conclusions: Neoadjuvant chemoradiation with SBRT and capecitabine to primary disease with RNI is feasible and provided a promising signal of durable local control in our study, despite high rates of pathological nodal involvement.Further investigation of this strategy is warranted in a larger cohort of patients.Clinical trial information: NCT1918644.Research Sponsor: None.Results of a phase II, open-label pilot study evaluating the safety and activity of liposomal irinotecan (Nal-IRI) in combination with 5-FU and oxaliplatin (NALIRIFOX) in preoperative treatment of pancreatic adenocarcinoma (NEO-Nal-IRI study).First Author: Thomas J. George, UF Health Cancer Center, Gainesville, FL Background: Neoadjuvant treatment for resectable pancreatic cancer (PDAC) is increasing in acceptability, but a standard regimen has yet to be established.The modified FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) regimen often requires dose modifications, delays and growth factor support due to toxicity.Liposomal irinotecan injection (Nal-IRI) is FDA-approved with a well-tolerated safety profile in relapsed, refractory mPDAC.Neoadjuvant NALIRIFOX was safe, having met the primary study objective, with reasonable rates of treatment completion and surgical outcomes for this relatively high-risk group of pts.Additional analyses are ongoing and will be reported at the meeting.Clinical trial information: NCT03483038.Research Sponsor: Ipsen Pharmaceuticals; University of Florida Health Cancer enter P30CA247796.The management of inoperable pancreatic cancer (PC) is controversial.We sought to compare local progression (LP) for inoperable PC managed with chemotherapy (CHT) and/or stereotactic body radiation therapy (SBRT).Methods: This single-institution retrospective review analyzed 94 patients diagnosed with locally advanced (LA), medically inoperable, or metastatic PC between 2014 and 2022.Patients received CHT alone, sequential (seq) CHT + SBRT, or SBRT alone.The primary endpoints were LP and intervention due to local progression (ILP) from start of treatment. Obstructive symptoms needing intervention, percutaneous endoscopic gastrostomy tube, gastrojejunostomy, or bleeding needing transfusion were considered ILP.Primary tumor growth on imaging or ILP were defined as LP.Fine-Gray regression models with treatment received considered a time-varying covariate were used to compare ILP and LP between treatment groups where death without LP was treated as a competing risk adjusting for ECOG, stage, age and year of diagnosis.In the subgroup of patients who received SBRT, patients were stratified at the median time between diagnosis and receipt of SBRT, and risk of ILP and LP was compared between the groups using cause-specific cumulative incidence functions.Results: Of 94 patients, 51 had CHT alone, 21 received seq CHT + SBRT, and 22 had SBRT alone.The median year of diagnosis was 2019 (range, 2014 -2022).The median ECOG was 1 with worse ECOG in SBRT alone and seq CHT + SBRT groups (p = 0.012).There were more LA or metastatic cases in the CHT (78%) and seq CHT + SBRT groups (67%) compared to the SBRT group (23%) [p , 0.001].The median SBRT dose was 36Gy (range, 25 -40Gy) in 5 fractions.Rates of LP and ILP were higher for CHT alone (68.6%, 39.2%) compared to seq CHT + SBRT (42.9%, 38.1%) or SBRT alone (18.2%, 4.5%) [p , 0.001; p = 0.004] .Higher rate of ILP associated with an increasing year of diagnosis (HR = 2.03, p , 0.005) and younger age of diagnosis (HR = 0.922, p = 0.011).The median time to SBRT was 116 days.Early (, 116 days) vs late SBRT LP rates differed (ILP: 4.8% vs 30%, LP: 14.3% vs 40%).Cause-specific cumulative incidence functions showed that death without LP favored early vs late SBRT (p = 0.009).Additionally, death without ILP favored early vs late SBRT (p=0.011).Conclusions: LP rates are high among patients with inoperable PC.SBRT for inoperable PC provides reasonable local control.Early SBRT reduces the need for ILP before death compared with late SBRT.Further investigation into the role of SBRT for inoperable PC is necessary.Research Sponsor: None.Does metformin use effect overall survival for patients with pancreatic cancer?First Author: Ravi Ramjeesingh, Division of Medical Oncology, Nova Scotia Cancer Center, Dalhousie University, Halifax, NS, Canada Background: In Canada, the incidence of pancreatic cancer ranks 11 th amongst all cancers but has resulted in the third highest mortality.Despite advancements in both diagnostics and therapeutics, the 5-year overall survival rate of pancreatic adenocarcinoma (PDAC) remains under 10%.Emerging studies have begun to examine the role of the hypoglycemic medication metformin, in improving outcomes of patients with PDAC.In cell cultures, metformin has been shown to have direct growth-inhibitory actions on malignant cells, and previous retrospective studies have suggested a potential association between metformin use and increased overall survival in breast and prostate cancer.To identify if metformin plays a role in improving PDAC outcomes, we have conducted a retrospective review of PDAC in Nova Scotia, Canada.Methods: We conduced a retrospective study of 630 patients diagnosed with PDAC treated at the Halifax Infirmary (Halifax, Nova Scotia).Records of patients were reviewed and information regarding patient demographics, cancer staging, metformin use, date of diagnosis, and date of death were collected.Statistical analysis using the log rank method was done to determine if there was a statistically significant difference in overall survival between groups.Results: Among the 630 patients identified, there were 337 males and 293 females.The average age at time of diagnosis was 74.02 years.Despite suggestion that metformin use may improve survival in some cancers, we found no statistical improvement in mOS for metformin use in PDAC patients.Future research including a prospective study should be undertaken to confirm these results in a larger sample size.Research Sponsor: None.phaseII study of maintenance rucaparib in patients with platinum sensitive, advanced pancreatic cancer and a pathogenic germline or somatic variant in BRCA1, BRCA2 or PALB2: A four year survival update.First Author: Kim Anna Reiss, Abramson Cancer Center at the University of Pennsylvania, Philadelphia, PA Background: We previously reported the results of a single arm, phase II study of maintenance rucaparib in patients with advanced, platinum-sensitive pancreatic cancer and pathogenic germline or somatic BRCA1, BRCA2 or PALB2 variants (Reiss et al, JCO,2021).We now report the five year follow-up of this trial.Methods: Patients with advanced PC and a pathogenic germline or somatic variant in BRCA1, BRCA2 or PALB2 were enrolled in this single arm phase II study performed at the Abramson Cancer Center.Patients were required to have received $16 weeks of platinum-based treatment without evidence of platinum resistance, which was defined as growing lesions, new lesions or steadily rising tumor markers.Chemotherapy was discontinued and patients received rucaparib 600mg PO BID until progression or unacceptable toxicity.The primary endpoint was progression-free survival (PFS).Secondary endpoints included overall response rate (ORR), disease control rate (DCR) and overall survival (OS).Results: Of 42 evaluable patients, seven (16.7%) remain progression-free for over four years (5 gBRCA2, 1 sBRCA2, 1 gPALB2) of whom four (9.5%) have been progression-free for five years. Two of these four patients discontinued rucaparib due to adverse events after three and four years of therapy, respectively, without signs or symptoms of progression to date. At the cutoff date, we observe an mPFS 12.9 months, mOS 24.3 months, ORR 41.6% (9 PRs, 6 CRs), noting that three patients converted from partial to complete response since our prior publication. Two patients with ongoing responses succumbed to treatment-related MDS/AML following 2.1 and 4.8 years on study, respectively. Prior to receiving rucaparib, these individuals had received 13 and 10 months of cytotoxic chemotherapy for pancreatic cancer, respectively. Conclusions: Here we report the four year progression-free survival rate of maintenance rucaparib in patients with BRCA or PALB2 related pancreatic cancer. Our data suggest that a select portion of this patient population achieves highly durable clinical remissions. This finding is further highlighted by two patients who have discontinued rucaparib for adverse events one and two years ago, respectively, and have not had biochemical or imaging evidence of progression to date. Given the cost and risk of treatment-related leukemia associated with PARP inhibition, this data highlights the need to better understand the highly variable biology of patients with PC and BRCA or PALB2 variants, and raises the possibility of whether a very small, select group may be cured by PARP inhibitors.

The patients continued on FOLFIRINOX without pegfilgrastim from the fourth course. The primary endpoint was development of FN. The secondary endpoints included relative dose intensity (RDI), objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The threshold and expected development of FN were 20% and 7%, respectively, at a one-sided significance level of 0.10 and statistical power of 80%. Based on this hypothesis, we calculated the number of patients needed to be 33. Results: In total, 34 patients (20 male, median age 66 years) were enrolled from August 2017 to September 2021. Twenty-three patients were unresectable, and 11 were borderline resectable. FN developed in one patient. FOLFIRINOX can be continued safely with a low incidence of FN after discontinuing pegfilgrastim in PDAC patients who did not experience FN during the first three courses of FOLFIRINOX, if the drug dose is reduced appropriately for neutropenia from the fourth course. Clinical trial information: UMIN000028055. Research Sponsor: None. First Author: Rebecca A Snyder, The University of Texas MD Anderson Cancer Center, Houston, TX Background: Postoperative complications in patients with borderline resectable pancreatic cancer treated with neoadjuvant therapy and pancreatectomy in the national cooperative group setting have not been previously characterized. Further, the impact of preoperative hypofractionated radiotherapy on postoperative outcomes is largely unknown. We sought to quantify perioperative morbidity among patients with pancreatic cancer who received neoadjuvant modified FOLFIRINOX chemotherapy with or without hypofractionated radiotherapy on a multicenter clinical trial. In this national cooperative group study of patients with borderline resectable pancreatic cancer,postoperative complications following neoadjuvant chemotherapy, radiation, and surgical resection were consistent with rates previously reported by high-volume institutions and using large datasets. Multimodality trials of preoperative therapy for locoregionally advanced pancreatic cancer may be safely performed in the cooperative group setting.

Factors associated with the receipt of surgery in acinar cell carcinoma of the pancreas.First Author: Jasleen Kaur Chaddha, Creighton University School of Medicine, Omaha, NE Background: Acinar cell carcinoma of the pancreas (PACC) accounts for 1-2% of adult pancreatic tumors.Clinically, this malignancy presents as a hypersecretory syndrome as lipase is released into circulation.Median overall survival is 18 to 47 months.Aggressive surgical resection is associated with long-term survival in PACC patients.This appears to be the treatment of choice for most localized pancreatic cancers, however, there are no clear treatment guidelines or standardized protocols for PACC due to its rarity.Further, no significant study has analyzed the factors correlated with receiving this surgery.This study aims to uncover the possible factors associated with the receipt of tumor resection in patients with PACC.Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with PACC from 2004 to 2019 using the histology code 8550 as assigned by the Commission on Cancer Accreditation program.Kaplan-Meier, ANOVA Chi-Square, and Multilevel Logistic Regression were performed, and data were analyzed using SPSS version 29.Statistical significance was set at a = 0.05.Results: 1430 patients with PACC were queried.600(41.95%) patients received surgical resection.Surgical patients experienced longer overall survival than nonsurgical patients (87.5 months vs. 25.3 months, P , 0.01).Of the surgical patients, wider surgical margins and complete tumor resection were associated with improved survival (P,0.001).Stage I and II disease, well and moderately differentiated disease, and receiving treatment at an academic/research facility were associated with an increased likelihood of receiving surgery (P,0.001).Metastasis at the time of diagnosis was associated with a decreased likelihood of receiving surgery (P,0.001).Income status, race, insurance status, and age did not appear to be significant predicting factors of surgery.Of the initial sample, 219 (15.31%) patients received adjuvant chemotherapy, 8 (0.55%) patients received adjuvant radiation, and 4 (0.28%) patients received both adjuvant chemotherapy and radiation.Adjuvant therapies did not appear to impact the overall survival of PACC patients.Conclusions:This study confirms that tumor resection is associated with increased survival in patients with PACC.Improved survival with surgery is correlated to wider surgical margins and complete tumor resection.It appears that patients with well or moderately differentiated disease, stage I or II disease, and treatment at an academic/research facility are more likely to receive surgery.PACC patients with metastasis to distant sites are less likely to receive surgery.The efficacy of adjuvant therapy remains unclear.Further studies are needed to better understand the factors involved in receiving surgery and other treatment modalities as part of PACC treatment.Research Sponsor: None.PRIMUS-002:A multicentre, open-label, phase II study examining FOLFOX and nab-paclitaxel (FA) and nab-paclitaxel and gemcitabine (AG) as neoadjuvant therapy for (borderline) resectable pancreatic cancer (PC), focusing on biomarker and liquid biopsy development. First Author: Derek B. Grose, University of Glasgow, Glasgow, United Kingdom Background: There is increasing evidence suggesting benefit from a neoadjuvant approach to PC. However, the optimal regimen is unclear and will likely require a precision medicine approach. Platinum-containing regimens have shown survival benefit for PC, with occasional exceptional responders, but biomarkers (BM) of response are not well defined and treatment decisions are often based on patient performance status (PS) and co-morbidity. Tumors may show defective DNA damage response (DDR), conferring potential selective sensitivity to DNA-damaging agents (e.g. platinum) and newer targeted agents. We have shown that DDR deficiency (DDRd) is present in up to 20% of PC. This study aimed to exploit DDRd as a therapeutic vulnerability, with integrated analysis to define candidate BM for FA and AG response. Methods: Patients with resectable and borderline resectable PDAC patients who were deemed fit for potential surgery were recruited into the trial between April 2019 and July 2021. All had been molecularly profiled using the Precision-Panc Clinical Cancer Genome including a novel DDRd assay, and the transcriptome with longitudinal sampling (pre-, during, and post-treatment). Patients received either FA (nab-paclitaxel 150mg/m2 IV, oxaliplatin 85mg/m2, folinic acid 350mg flat dose, fluorouracil infusion 2400mg/m2 continuous IV infusion), or AG (nab-paclitaxel 125mg/m2, gemcitabine 1000 mg/m2) for 3 months, based on patient age and PS. The primary endpoint was disease progression (DP) during neoadjuvant therapy. Results: 31 patients in total were recruited into the trial unfortunately the trial was terminated early due to funding issues. The median age was 62 years old (31-73) 21 patients were male and 10 female. 7 resectable cases and 24 borderline resectable at diagnosis were included in the study. 26 patients were recruited to the FOLFOX-A arm and 5 to the AG arm. Following chemotherapy 6 patients had partial response, 17 stable disease and 6 progressive disease.

Biweekly gemcitabine plus nab-paclitaxel as first-line therapy for older adult patients with unresectable pancreatic cancer: A prospective study.First Author: Kenji Ikezawa, Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan Background: Although the number of older adult patients (aged $ 75 years) with pancreatic cancer (PC) is increasing, there are still limited data regarding chemotherapy for these patients, who experience adverse events more frequently than younger patients with PC.In this study, we evaluated the efficacy and safety of biweekly gemcitabine plus nab-paclitaxel (GnP) as first-line therapy for older adult patients with unresectable PC.Methods: We conducted a single-center prospective study.Stereotactic body radiotherapy compared to conventionally fractionated radiotherapy for locally advanced or oligometastatic pancreatic cancer.First Author: Ofri Mizrahi, Hadassah Hebrew University Medical Center, Jerusalem, Israel Background: Pancreatic cancer, particularly in its locally advanced and oligometastatic forms, poses a formidable therapeutic challenge.Radiotherapy remains an important treatment in an attempt to gain local control, however there is no consensus on whether stereotactic body radiotherapy (SBRT) is appropriate as compared to conventionally fractionated radiotherapy (CFRT).Herein, we report our experience. Methods: We conducted a retrospective analysis of patients with locally advanced and oligometastatic pancreatic cancer who received definitive radiotherapy at our institution between Several treatment characteristics and dosimetric factors such as sex, age, receipt of chemotherapy, type of chemotherapy, use of elective nodal irradiation, GTV size, biologically equivalent dose (BED) corrected prescribed dose, minimum dose to GTV, or max dose to GTV did not predict local failure.There was no difference in QOL and toxicity between the two groups.Conclusions: In our cohort, local failure rates remain high and were similar between patients treated with SBRT compared to those treated with conventionally fractionated radiotherapy.We were unable to identify any specific predictors for local recurrence in this patient population.Our observation of a lower CSM rate among patients who received SBRT needs further study.The findings underscore the need to further improve radiotherapeutic approaches in an attempt to improve local control in locally advanced disease.Research Sponsor: None.Prognostic factors for GEM + nab-PTX combination therapy in elderly patients with pancreatic cancer. First Author: Kazuki Watabe, Chiba University Hospital, Chiba, Chiba, Japan Background: Japanese Clinical Practice Guidelines for Pancreatic Cancer 2022 recommends gemcitabine (GEM) + nab-paclitaxel (nab-PTX) therapy (GnP regimen) as the first line chemotherapy for elderly patients with pancreatic cancer. In Japan, it is reported that about 69% of pancreatic cancer patients are elderly, and Only few group reported the safety of GnP regimen. In this study, we investigated the anti-tumor efficacy and prognostic factors of GnP regimen in patients with pancreatic cancer at our hospital, with a particular focus on age. Methods: 160 patients who started GnP therapy as the first line treatment for unresectable pancreatic cancer between February 2016 and December 2021 were included in the study. 70 years of age or older was defined as elderly, and patient background and treatment efficacy were compared in two groups: non-elderly patients (n=84) and elderly patients (n=76). Prognostic factors were also compared between the overall population and the elderly. Results: Patients with a primary lesion in the pancreatic head were 32 (38.1%) of the non-elderly patients and 35 (46.1%) of the elderly patients. 60 patients (71.4%) of the non-elderly and 38 (50.0%) of the elderly had distant metastases. The median overall survival was 16.0 months for the non-elderly and 17.7 months for the elderly, with no significant difference (p=0.93). GnP regimen in pancreatic cancer can be expected to have the same antitumor effect in elderly patients as in non-elderly patients. However, significant prognostic factors were reduced in the elderly, we need to identify specific factors to determine the indication for treatment in the elderly patients. Research Sponsor: None.

First Author: Jose Antonio Lopez Guerrero, Instituto Valenciano de Oncología (IVO), Valencia, Spain Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by its immunologically cold tumor microenvironment (TME) with scarce T cell infiltration and few molecular signatures of immune activation.To date, the immunotherapies including the immune checkpoint blockade of PD-1, and CTLA-4 either single or in combination have shown modest results in PDAC tumors.Recently, the Lymphocyte Activation Gene (LAG3) has emerged as a promising checkpoint target as indicated by preclinical and clinical data.The aim of this study is to explore the immune profile of a series of PDAC and to evaluate its prognostic impact.This predictive model was independently validated in the PDAC dataset of the Cancer Genome Atlas (TCGA) (p,0.0001).Interestingly, cluster 1, was characterized by the significant overexpression of LAG3 which has recently been proposed as the next immune checkpoint (IC) receptor target.Moreover, Cluster 1, exhibited the overexpression of other ICs such as PD1, PD-L1, IDO1, LIF and CTLA4, defining cluster 1 as an immunologically hot tumor.IHC for LAG3 and other ICs showed a moderate correlation with HTG results.Conclusions: In this study, a prognostic transcriptomic-based signature of 14 genes has been defined and validated for PDAC.This signature clearly identifies two prognostic groups that could constitute the basis for tailored immunotherapy with specific IC inhibitors.LAG-3 is a promising target for immunotherapy in PDAC patients.Research Sponsor: H2020-FETOPEN-2018-2019-2020-01 Contract no: 899708.Pulsed low dose rate radiation to mitigate tumor-permissive responses in pancreatic cancer-associated fibroblasts: Introducing the HOST-factor. First Author: Edna Cukierman, Fox Chase Cancer Center, Philadelphia, PA Background: Pancreatic ductal adenocarcinoma (PDAC) features a distinctive tumor microenvironment comprising cancer-associated fibroblasts (CAFs) and their selfproduced extracellular matrix (ECM), forming functional CAF units (CAFu). The current total neoadjuvant therapy (TNT), involving conventional chemoradiotherapy (CRT), yields suboptimal responses while promoting a tumor-permissive CAFu state. To address this, we explored pulsed low dose rate radiation (PLDR)-based TNT, as an alternative to CRT, to treat three-dimensional in vivo-like human PDAC CAFu cultures. We assessed gemcitabine combined with PLDR versus CRT using theHOST Factor, a "harmonized output of stroma traits" factor, comprising several established CAFu functional indicators, which inform on the functional status of the PDAC microenvironment. Methods: The unique CAFu functional values used corresponded to: i) ECM anisotropy; ii) persistent cell-ECM signaling; iii) sustained cytokine-induced activation; iv) cytoskeletal bundling; and v) systemic features of fibroblastic activation. The validity of the resultant HOST factor was assessed using the unit's ECM ability to elicit fibroblastic activation, indicated by a high aSMA/F-actin ratio value. Results: Ex-vivo CRT led to a HOST factor that was 2-fold greater than chemotherapy alone (p=0.6), which was functionally gauged as a tumor-permissive CAFu. In contrast, PLDR averted CRTinduced tumor-permissive response and established a 6-fold lower HOST factor, suggestive of a "normalized" CAFu, when compared to the HOST factor value established when using conventional TNT (P=0.0016 vs. CRT, and P= 0.0086 vs. gemcitabine alone). The multi-parameter HOST factor validity was confirmed as CRT treated CAFu's ECM activated human pancreatic fibroblasts (aSMA/F-actin = 70% 6 29) while PLDR-treated CAFu's ECM failed to do so (aSMA/F-actin = 32% 6 26), reaching a 30% mean rank difference (P ,0.0001). Conclusions: PLDR mitigates conventional CRT-based TNTinduced tumor-permissive responses, restoring the fibroblastic units' tumor-suppressive function. These results lend support to a phase 1 trial designed to evaluate whether radiation with PLDR-based TNT, constitutes a safe and more effective treatment for PDAC patients. The novel HOST factor is being used to appraise specimens from NCT04452357. Research Sponsor: NIH/NCI R01CA269660; Fox Chase Cancer Center Translational Research Award.

The expression of various PanC-related miRNAs in sEV was heterogenous and correlated with corresponding clinical parameters, including treatment response and overall survival.Conclusions: Neoadjuvant chemotherapy in combination with SBRT is safe and tolerable regimen to treat patients with locally advanced and borderline PanC.Further, sEV in the plasma of PanC patients could serve as useful prognostic and predictive markers.Research Sponsor: None.Lymphopenia and spleen dose for patients with inoperable pancreatic cancer receiving ablative 5-fraction radiation therapy. First Author: Michael David Chuong, Miami Cancer Institute, Baptist Health South Florida, Miami, FL Background: Treatment-induced lymphopenia in pancreatic ductal adenocarcinoma (PDAC) patients after radiation therapy (RT) may negatively impact overall survival (OS). While non-ablative RT (NA-RT) is routine for borderline resectable (BRPC) and locally advanced (LAPC) PDAC, ablative RT (A-RT) has garnered increasing interest based on data suggesting improved clinical outcomes including OS. Absolute lymphocyte count (ALC) changes after A-RT and the potential association with spleen dose in this setting have not been previously described.

Unlike PDAC, PACC is a genomically diverse disease, with potentially targetable alterations in RAF, HRD, and MMR genes, offering additional therapeutic options for significant number of pts.In addition, more than one-third of the pts harbored germline mutations in HR genes.Therefore, somatic and germline testing should be considered for any pt diagnosed with PACC.Research Sponsor: None.The prognostic value of mutational signatures in pancreatic cancer. First Author: Nicholas Light, University of Toronto, Toronto, ON, Canada Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor overall survival (OS), however there are significant outliers. Understanding the biological factors driving PDAC cancer may reveal new biomarkers and treatment strategies. Mutational signatures, imprinted in the cancer genome, encode the life history of the cancer and may be used to stratify tumors into clinically-relevant subgroups. Methods: In this study we performed mutational signature analysis (MutationalPatterns, COSMIC v3.3) on whole genomes from 434 PDAC patients, comprising 167 patients with resected primary tumors, and 267 advanced PDACs from patients enrolled in the COMPASS trial. We evaluated whether the mutational signatures detected associate with OS using the logrank test in the overall cohort and stratified by disease stage, adjusting for multiple hypotheses with 5% false discovery rate (FDR). We further characterized these associations in exploratory analyses. Results: Among the 55 COSMIC signatures detected in the overall cohort, the presence of three signatures significantly associated with OS after We identified three mutational signatures-SBS85, SBS93, and SBS33-that have not previously been described in PDAC and associate with OS. Further characterization of these novel signatures in PDAC and their underlying biology may uncover new treatment avenues. Research Sponsor: None. First Author: Ashish Manne, The Ohio State University Comprehensive Cancer Center, Columbus, OH Background: MUC5AC is a gel-forming glycoprotein that exists in two major glycoforms in PDA. We studied the differential expression and predictive value of heavily glycosylated mature MUC5AC (MM) detected in the apical (Ap) and/or extracellular region (EC) and less-glycosylated immature MUC5AC (IM) detected only in the cytoplasm (Cy) in R-PDA. Methods: R-PDA formalin-fixed paraffin-embedded tissue blocks from January 2010 to June 2021 were obtained from the Ohio State University biorepository. Immunohistochemistry was performed to study the expression for MM and IM using monoclonal antibodies 45M1 and CLH2, respectively, and H-scores were calculated. UpS group. IM levels were directly proportional to the response (near complete (mean H-score 98) , partial (105) , NR (152) , UpS (162), p=0.04). Other TR results are discussed in the table. Conclusions: MUC5AC (IM . MM) is a potential predictive marker for TR among PDA patients, specifically among those receiving FOLFIRINOX. These associations must be validated in further prospective studies. Research Sponsor: IRP, Pelotonia.

Outcomes in patients with pancreatic and ampullary cancer whose tumors harbor pathogenic APC mutations.First Author: Christopher Pishvaian, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD Background: APC (adenomatous polyposis coli) is master regulator of the WNT signaling and beta-catenin pathway.Pathogenic (path) mutations in APC are well known for their connection to familial adenomatous polyposis, but germline (G) mutations in APC can give rise to other cancers, and somatic (S) mutations in APC can be found in multiple cancer subtypes.The clinical relevance for tumors that harbor path APC mutations is unknown.Methods: An established database of patients whose tumors have undergone genetic testing (Next-generation DNA sequencing, NGS) was queried for the presence of an APC mutation.Each APC mutation identified was assessed using the NCI Clinvar data base for determination of a path/likely path APC mutation.Patient/disease characteristics and treatment (tx) information were captured from electronic medical record review.Median overall survival (OS) was defined from the time of diagnosis of advanced/metastatic disease until death.Median time to progression (TTP) for each tx regimen was defined from the initiation of tx until documented disease progression.Results: A database of over 13000 patients entered from 2018 to present included 133 patients (1%) with G-or S-APC mutations, of which 41 were identified as path/likely path.Of the 41 patients, 56% were male, 73% were Caucasian and 24% African Americans, with a median age of 67 (range 34-90).Only 32% of patients had known G-APC mutations, but 34% had a second primary cancer, and 37% had a family history of known G-APC mutation-associated cancers.Only one patient had clinical manifestations of a polyposis syndrome.Of the 13 patients with known G-APC mutations, clinical characteristics were similar to the larger group, except that 100% of the G-APC-mutated patients were Caucasian, and the rate of family history of APCassociated cancers was 54%.Fifty-four percent of the overall group of 41 patients had a pathological diagnosis of pancreatic cancer, while the remaining 46% were ampullary or duodenal cancers.(Only 2 patients [5%] had tail of the pancreas cancers).Of the 37 patients who had somatic tumor NGS, only 70% harbored a KRAS gene mutation.For the OS analysis (n=24), the mOS was 11.7 months (range 5.2 -56.9).Of the 22 patients evaluable for TTP, the mTTP for 5FU-based tx was 5.8 months, and 6.4 months for gemcitabine-based tx.Conclusions: APC-mutated pancreatic and ampullary cancers are uncommon, but exhibit survival rates, as well as TTP on both 5FU and gemcitabine-based txs that are similar to that seen with most pancreatic adenocarcinomas.However, 30% of APC-mutated cancers are KRAS wild type, and may harbor other driving mutations.As the loss of APC function triggers an accumulation of beta-catenin, targeted therapies that inhibit beta-catenin-regulated transcription and downregulate WNT-related signaling could be a promising tx approach for patients whose tumors harbor path/likely path APC mutations.Research Sponsor: None.1%) and WT (11.6%).ATM mutations as well as an expanded set of genomic alterations within the DDR pathway were also enriched with similar trends (GOF,LOF,WT).Other potentially confounding factors will be discussed in the context of multivariate OS/PFS analyses.Conclusions: TP53 mutations correlated with worse prognosis in advanced PDAC.Potential predictive associations favoring FFX over GA in the TP53 LOF subgroup (but not in GOF or WT subgroups) warrant further exploration.Research Sponsor: Pancreatic Cancer Action Network; Perthera. PDAC is associated with a high recurrence rate even after curative-intent surgical resection and perioperative chemotherapy. Detection of MRD in this setting can inform prognosis and may be actionable for innovative targeted therapies or additional chemotherapy to improve outcomes. While CA19-9 may detect disease before it is clinically apparent, it lacks specificity and up to 20% of patients (pts) are non-producers. ctDNA has been shown to be useful for MRD detection in other cancers but its utility in PDAC is not established. Methods: Pts with PDAC who had a commercial ctDNA assay (Natera) after completion of all curative-intent therapy (surgery and chemotherapy) in the MRD setting were included. Recurrence and survival data were correlated with the end-oftreatment (EOT) ctDNA result. Published literature and abstracts for studies examining ctDNA for MRD detection in PDAC using the same testing platform were identified. Available data were pooled to determine EOT ctDNA positivity rate, positive and negative predictive values (PPV, NPV), and lead time from a positive ctDNA to documented recurrence. Results: A total of 33 pts had EOT ctDNA samples collected at our institution. At EOT, ctDNA was + in 30.3% (n = 10). At a median follow-up time of 14.3 months, median recurrence free survival (RFS) for + vs negative ctDNA was 3.6 vs 25.1 months (HR = 15.

Characterizing the genomic landscape of locally advanced pancreatic cancer.First Author: Galileo Arturo Gonzalez Conchas, Princess Margaret Cancer Centre, Toronto, ON, Canada Background: Locally advanced pancreatic cancer (LAPC) accounts for approximately 30% of pancreatic ductal adenocarcinomas (PDAC).Optimal management for LAPC is controversial and combination treatments are extrapolated from treatment guidelines for metastatic disease.The biological underpinnings of LAPC remain unclear, although the loss of tumor suppressor SMAD4 has been associated with metastatic disease.Here we characterize the genomic landscape of LAPC in a large series of prospectively sequenced PDAC.Methods: Clinical, genomic and survival data were obtained from the COMPASS trial (NCT02750657), a prospective multi-institutional study that included patients with treatment-naïve advanced PDAC, with predominantly metastatic cases due to ease of biopsy.Fresh tumor tissue was acquired by percutaneous core biopsy for real-time whole genome sequencing (WGS) and RNA sequencing (RNAseq).Laser capture micro-dissection was performed for all cases.Response to therapy was assessed every 8 weeks, and patients were followed prospectively.Results: Of 268 patients (268 with available WGS and 253 with RNAseq), 37 (14%) had LAPC.Baseline epidemiological variables were similar, with no differences between sex, age, smoking status, or history of diabetes.Patients with LAPC had a lower BMI (median 22 vs 24, p=0.005) and lower baseline CA19-9 (median 488 vs 2551, p=0.002) than metastatic cases.All patients with LAPC had a low (,2 points) Gustave Roussy Immune Score, previously shown to be prognostic in our dataset.Driver alternations were similar in LAPC and metastatic cases with no differences in SMAD4 loss between the two groups; however, major imbalances in mutant KRAS were absent in the LAPC group.The burden of SNVs, indels and SVs was significantly lower in LAPC (Table).All LAPC cases demonstrated a classical RNA subtype, compared to 23% in metastatic cases (p=0.0008).Median OS measured 12.5 and 8.3 months for LAPC and metastatic cases, respectively (HR 0.65, 95% CI 0.48-0.89,p=0.003).In addition, when measuring CD8+ T cell infiltration by IHC using median cut-off values, primary site biopsies had a higher CD8+ T cell infiltrate compared to metastatic sites (77% vs 56% CD8-high, respectively, p=0.01).Conclusions: These integrated genomic, RNA subtyping and early immunophenotyping results suggest that LAPC demonstrate less genomic instability and classical programming.Further study will delineate how these genomic differences, along with better clinical features, may influence treatment decision-making and design of future clinical trials.Clinical trial information: NCT02750657.Research Sponsor: Ontario Institute for Cancer Research.The impact of Wnt pathway alterations including RNF43, GNAS, CTNNB1, and APC on prognosis and potential therapeutic vulnerability in pancreatic adenocarcinoma (PDAC).First Author: Naoko Takebe, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD Background: Several Wnt pathway genes (RNF43, GNAS, CTNNB1, APC) are mutated in PDAC but their clinical implications remain unclear.Both RNF43, a membrane E3 ubiquitin ligase that negatively regulates Wnt via FZD, and GNAS, a mediator of GPCR signaling, are enriched in IPMN-associated PDAC whereas CTNNB1 is a hallmark of solid pseudopapillary neoplasms.Here, we retrospectively analyzed progression-free survival (PFS) and overall survival (OS) in a PDAC cohort to understand potential therapeutic and prognostic differences between tumors with (MUT) or without (WT) Wnt pathway mutations.Methods: We analyzed longitudinal outcomes across 774 patients (pts) with NGS results from Perthera's Real-World Evidence database who received at least 1 line of therapy in the advanced setting for PDAC.PFS was evaluated from initiation of 1st line for advanced disease until discontinuation due to disease progression.Hazard ratios and p-values were computed via Cox regression when comparing PFS within subsets that received either 1st line FOLFIRINOX (FFX) or 1st line gemcitabine/nab-paclitaxel (GA).Differences in frequencies of genomic alterations outside the Wnt pathway were analyzed by Fisher's exact test.Results: Within the analysis cohort (N = 774), Wnt pathway alterations were present in 72 (9.3%) of PDAC tumors based on mutations in either RNF43 (4%), GNAS (3%), CTNNB1 (,1%), or APC (2%). Median OS (relative to advanced diagnosis) was significantly longer in the MUT subgroup compared to WT (Table).Median PFS on 1st line GA was significantly longer in MUT pts, and a similar insignificant trend was noted for PFS on 1st line FFX (Table).MSI-high and PIK3CA mutations were enriched for co-occurrence with Wnt pathway alterations whereas common PDAC mutations in KRAS and TP53 were less frequent in MUT pts (Table). Gene-specific trends and potential confounders will be discussed in the context of multivariate OS/PFS analyses. Conclusions: The presence of Wnt pathway alterations identifies a subgroup of advanced PDAC with improved PFS and OS. Research Sponsor: Pancreatic Cancer Action Network; Perthera. of mPFS on 1st line therapies (GA or FFX), mOS relative to advanced diagnosis, and frequencies of co-occurring mutations (%) between patients with Wnt pathway alterations (MUT) or without (WT).

Among expert radiologists, RECIST score CCC was 0.77 [95% CI: 0.59-0.88],whereasimage registration QIB CCC values were significantly higher (DV: 0.95 [0.90-0.98],p=0.002;DB:0.93 [0.86-0.97],p=0.014).DV and DB QIB measured by direct tumor segmentation had significantly lower CCC than by image registration (p,0.001).Among novice readers, image registration QIB (DV: 0.83 [0.67-0.91] ,DB:0.70 [0.48-0.84])producedhigher agreement than RECIST (0.26 [-0.17-0.61];p=0.002and p=0.035), with CCC more similar to expert readers.While image registration QIB did not differ from RECIST in association with RFS, registration-based QIB predicted OS with significantly higher C-index (DV: 0.58 [0.56-0.60],p,0.001;DB:0.64 [0.62-0.66],p,0.001)than) among experts. Conclusions: Longitudinal registration of the pancreas yields more consistent QIB for PDAC TR with stronger association to OS outcomes than RECIST. These registration-based QIB aim to advance PDAC management by improving patientspecific discrimination of TR after NAT. Research Sponsor: National Institutes of Health P30CA008748; National Institutes of Health P50CA257881; RSNA R & E Foundation.

Predicting rapid progression and overall survival in stage II-III pancreatic cancer using a CT-based radiomic signature.First Author: Qinmei Xu, Stanford University School of Medicine, Stanford, CA Background: We sought to assess the ability of a computed tomography (CT)-derived radiomic signature (RS) feature set to predict rapid tumor progression and overall survival (OS) in patients diagnosed with stage II-III pancreatic cancer undergoing stereotactic body radiation therapy (SBRT) in sequence with chemotherapy.Methods: We conducted a retrospective study on a cohort of 240 stage II-III pancreatic cancer patients who underwent SBRT in sequence with chemotherapy at a single institution (Stanford Hospital and Clinics).Among them, 83 had pre-SBRT contrast-enhanced CT images with segmented tumors, forming the imaging set, from which we extracted 900 radiomic (quantitative pixel-level imaging characteristic) features from delineated tumor regions-of-interest.For RS development, we divided the imaging set into a training set (n = 53) for model development and a test set (n = 30) for evaluation.We built a binary prediction model on the training set to identify patients at risk of rapid tumor progression within three months after SBRT.We utilized logistic regression with the Least Absolute Shrinkage and Selection Operator algorithm for feature selection and classification.To fine-tune parameters, we performed five-fold cross-validation on the training set, repeating each set of parameters five times.Finally, we assessed the model's performance on the test set (n = 30) using the area under the curve (AUC) value.We selected the model with the best AUC, while also generating the predictive radiomic feature set. For OS prognostication, we conducted both univariate and multivariate Cox proportional-hazards analyses using RS and clinical features (age, sex, stage, vessel involvement, tumor location, performance status, body mass index, biological equivalent dose of radiation) as potential predictors.Results: The enrolled cohort consisted of 127 men (mean age, 69 years 6 12 [SD] ) and 113 women (mean age, 69 years 6 13 [SD]).Seventeen textural radiomic features were identified as the RS, which demonstrated a high AUC in the test set for the prediction of rapid progression (AUC 0.850; 95% CI: 0.725, 0.975).Age was associated with OS in the multivariate model while high RS (.0.5) was independently associated with OS in both univariate and multivariate models.Conclusions: CT-derived RS, combined with age, represent the most prognostic factors for stage II-III pancreatic cancer.RS, which likely reflects underlying biology or molecular alterations, contributes to the highest HR of poor OS and provide the strongest indicator of outcome following commonly used treatments in this patient population.Research Sponsor: None.Contribution of neoadjuvant chemotherapy and radiation therapy (intensitymodulated radiation therapy with concurrent chemotherapy versus stereotactic body radiation therapy alone) on tumor volume regression in patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma: A single institution experience.First Author: Jacob K. Jamison, Weill Cornell Medical College, New York, NY Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis with a minority of patients (pts) eligible for curative resection.Pts with borderline resectable or locally advanced (BR/LA) PDAC frequently receive neoadjuvant chemotherapy (NAC) +/radiation therapy (RT) to improve resectability.Here, we report the individual contribution of NAC and RT (either intensity modulated RT + concurrent chemotherapy (IMRT+CC) or stereotactic body RT (SBRT) alone) on tumor regression by measuring tumor volumes.Methods: We performed a single institution retrospective review of PDAC pts who underwent resection between 2011-2021 and were part of a tumor biobank registry.Tumor measurements were performed at baseline, post-NAC, and post-RT by five independent, blinded abdominal radiologists.Analyses were performed using paired t-tests, twoproportion z-tests, log-rank tests, and Mann-Whitney U test.Results: We identified 49 BR/LA pts who received NAC followed by RT who had complete pre-and post-treatment imaging.Fifteen pts received IMRT+CC and 28 received SBRT.The effect of NAC on tumor volumes (-29.2%vs-26.3%,p=0.66;mean percent change) and maximum diameter (-9.2% vs -12.0%, p=0.58) was similar within the IMRT+CC and SBRT groups.Both IMRT+CC (-7.12 cm 3 , p=0.003) and SBRT (-2.70 cm 3 , p=0.001) resulted in significant tumor regressions.IMRT+CC achieved a significantly greater overall mean percent change in tumor volume(-53.4% vs -28.8%, p=0.024) and maximum diameter(-30.4%vs -16.2%, p=0.020) compared to SBRT. Pts receiving IMRT+CC or SBRT had similar tumor volumes (10.88 vs 11.74 cm 3 , p=0.87, respectively) and maximum diameter (3.45 vs 3.17 cm, p=0.48) prior to RT. IMRT+CC resulted in improved tumor volume response (.30% regression; 80.0% vs 46.4%; p=0.033) but not an improved response rate by RECIST criteria (46.7% vs 21.4%; p=0.085). Mean resected tumor volumes (by pathological review) for those receiving IMRT+CC (n=9) and SBRT (n=23) were 4.34 vs 13.1 cm 3 (p=0.049). The R0 (86.7% vs 85.7%, p=0.93) and N0 (73.3% vs 53.6%, p=0.21) resection rates between the two groups were similar. Compared to SBRT, IMRT+CC resulted in an improved recurrence free survival (RFS; 2.36 vs 1.31 years; p=0.026), but did not meet statistical significance for an overall survival benefit (mOS; 2.85 vs 2.03 years, p=0.19). Conclusions: We found that IMRT+CC yielded superior radiographic volumetric regression and improved RFS but did not significantly impact mOS. Correspondingly, resected tumors from patients treated with IMRT+CC were smaller than those obtained from patients treated with SBRT. The role of IMRT+CC and SBRT in PDAC remains to be clearly defined. Research Sponsor: None.

KRAS mutation status in the prediction of pancreatic tumor response after neoadjuvant systemic therapy and magnetic resonance-guided SBRT.First Author: Amit Jethanandani, The University of Miami Sylvester Comprehensive Cancer Center, Miami, FL Background: Stereotactic body radiotherapy (SBRT) has been incorporated into multimodality treatment of locally advanced and borderline resectable pancreatic ductal adenocarcinoma (PDAC).For non-metastatic inoperable PDAC patients (pts) who receive magnetic resonance-guided SBRT (MRgSBRT), baseline features that predict for treatment response remain unsettled.In localized PDAC, multiple studies have investigated the KRAS oncogene as a prognostic factor with mixed findings.In this single institution retrospective study of PDAC pts treated with MRgSBRT, we hypothesized that KRAS mutation status would be predictive of meaningful clinical outcomes.Methods: From an IRB approved dataset of PDAC pts treated with MRgSBRT between 2016 and 2022, 39 pts with nonmetastatic inoperable pancreatic cancer, known KRAS mutation status, $ 3 months of neoadjuvant systemic therapy (NST), and at least 3 months post-RT follow up were extracted for analysis.Baseline demographics, tumor and treatment characteristics, and clinical endpoints including conversion to resectability, best imaging response per RECIST v1.1, pathologic response (PR) per TRG-CAP, and overall survival (OS) after MRgSBRT were collected.Objective response (ORR) on both imaging and pathology was defined as complete response (CR) + partial response (PR); disease control (DC) was defined as CR + PR + stable disease (SD).Logistic regression was used to assess correlation between baseline variables and ORR.Cox proportional hazard models were utilized to determine association with OS. Results: Out of 39 pts, 21 (53%) were KRAS-mutated (KRAS-mt) and 18 (47%) were KRAS wild-type (KRAS-wt).Median age was 62, 54% were male, only 1 pt had ECOG .1, and CA 19-9 at diagnosis was 197.Median duration of NST was 9 cycles, and common agents included Gemcitabine and Abraxane (21%); FOLFIRINOX (28%); a combination of the two regimens (41%); or other NSTs (10%).Median MRgSBRT dose fractionation was 50 Gy (range 35 -50) in 5 fractions; all fractions underwent adaptive optimization.Thirty pts (77%) experienced DC on imaging, 16 (43%) had ORR, and 12 (31%) were converted to resectable following MRgSBRT.Cohort median OS was 12.3 months, and pts who had surgery had a non-significant median OS advantage (18 vs 12 months; p=0.19).KRAS-mt was associated with worse ORR (p=0.04;AUC=0.73)and decreased OS (HR: 2.15; p=0.03).In a clinical model incorporating baseline characteristics (age, ECOG, radiographic staging, CA 19-9 level, and KRAS), only KRAS predicted OS (HR: 3.02 for KRAS-mt; p=0.01).KRAS-mt status was also predictive of OS among pts who underwent surgery (HR: 5.24 for KRAS-mt; p=0.04).Conclusions: For localized PDAC pts inoperable at diagnosis who received NST followed by MRgSBRT, KRAS was the only significant predictor of ORR and OS, highlighting the need for further treatment intensification in KRAS-mt pts.Research Sponsor: None.TPS710Trials in Progress Poster Session Epidemiological characteristics of gastric and pancreatic cancers in Latin America: The LACOG 0222 GASPAR study. First Author: Renata D'Alpino Peixoto, Grupo Oncoclínicas, S ão Paulo, Brazil Background: Gastric and pancreatic tumors remain among the cancers with the poorest prognoses in both high and low/middle-income countries. Data on the clinicopathological characteristics, standard treatments, and outcomes of these tumors are scarce in Latin America. This study is the first comprehensive effort to report epidemiological and clinical data in this region. Methods: The LACOG 0222 GASPAR trial (NCT05924789) is a retrospective and prospective (bidirectional) observational cohort study. Enrollment of 200 patients across 15 sites in Latin America is planned, 120 patients in cohort A (gastric cancer) and 80 patients in cohort B (pancreatic cancer). No interventions are proposed. Eligibility criteria include age $18 years, histological diagnosis of gastric and gastroesophageal junction cancer (cohort A) or pancreatic cancer (cohort B), advanced disease diagnosis since January 2019, and availability of adequate medical data for data collection. The primary objective is to describe the clinical characteristics, treatment patterns, and outcomes of patients with gastric and pancreatic cancer in Latin America. Data on patients' clinical characteristics, demographics, tumor pathological features, surgical therapy, radiotherapy, chemotherapy, and target therapy will be collected.

Treatment response is assessed via RECIST 1.1 criteria with surveillance CT prior to enrollment and after completion of two cycles(8 weeks).Baseline and on-treatment tumor biopsies (after completion of one cycle, 4 weeks) are performed to analyze changes in immune, stromal, and genomic profiles to elucidate mechanisms of treatment response and failure.Patient reported outcomes are incorporated (FACT-Hep and FAACT subdomains) to assess disease-specific symptoms.To date, 7 patients have been enrolled(Clinical Trial NCT05102721). Clinical trial information: NCT05102721. Research Sponsor: Gateway for Cancer Research, Conquer Cancer Foundation ASCO; Vaccinex.

Methods: COVALENT-102 (NCT05631574) is a prospective, openlabel, dose-finding study evaluating the safety, tolerability, and clinical activity of BMF-219 administered daily in adults with unresectable, locally advanced, or metastatic NSCLC (Cohort 1), PDAC (Cohort 2) and CRC (Cohort 3) with activating KRAS mutations who have received standard therapy.All indications as a group follow a 3+3 dose escalation design.BMF-219 is orally administered once or twice daily as continuous therapy in 28-day cycles until progression or intolerability/unacceptable toxicity.Following dose-escalation, each indication will enroll patients in expansion cohorts independently to obtain further safety and efficacy data.Eligible patients include those with any KRAS mutation and (Cohort 1) stage IIIB/IV NSCLC with 2-4 prior lines of therapy including immune checkpoint inhibitors (ICI) & /or platinum-based chemo 6 bevacizumab with ECOG 0-2; (Cohort 2) stage III/IV PDAC with $ 1 prior line of therapy including either FOLFIRINOX or gemcitabine/nabpaclitaxel, ECOG 0-1; or (Cohort 3) stage III/IV CRC with $ 1 prior line of therapy including FOLFOX or FOLFIRI 6 bevacizumab (prior ICI if MSI-H/dMMR), ECOG 0-2.Patients must have documented progression and measurable disease as defined by RECIST 1.1.Patients with prior KRAS inhibitor exposure are eligible.Key exclusion criteria include untreated CNS metastasis, prior menin inhibitor therapy, and clinically significant cardiovascular disease.The primary objective is to determine the optimal biological dose/ recommended Phase 2 dose of BMF-219 monotherapy.Secondary objectives include further evaluation of safety and tolerability, characterization of the PK/PD of BMF-219, and efficacy based on duration of response and disease control rate.PFS, OS, and time to response are exploratory endpoints.Accrual began in January 2023 and is ongoing.Clinical trial information: NCT05631574.Research Sponsor: Biomea Fusion.A phase II telemedicine study of pemigatinib in adult patients with unresectable or metastatic pancreas cancer with FGFR2 gene fusions or other FGFR genetic alterations.First Author: Zachary Risch, The Ohio State University, Columbus, OH Background: Advanced pancreas cancer has a poor prognosis with few effective targeted therapies.Given this current state, novel therapies for pancreas cancer are an unmet need.Genomic alterations in FGFR, including fusions and point mutations are known driver mutations in cancer.FGFR kinase inhibitors have been FDA approved in cholangiocarcinoma and urothelial carcinoma, however, have not been well studied in other cancers.Our team previously identified and treated four patients with advanced pancreas cancer and FGFR2 fusions with FGFR kinase inhibitors resulting in durable responses and prolonged survival.Additionally, through a review of Foundation Medicine's clinical genomic database, consisting of 30,229 pancreas cancer tumors, we determined that FGFR1-3 fusions have a prevalence of approximately 1% in pancreas cancer, most commonly in FGFR2 (0.8%).Our observations provide preliminary evidence that FGFR targeted therapy results in excellent clinical outcomes.We hypothesize that FGFR altered pancreas cancer treated with a FGFR kinase inhibitor will result in durable responses.We developed a phase 2, telemedicine trial of pemigatinib, an FDA approved FGFR kinase inhibitor, in FGFR altered pancreas cancer.Since the COVID-19 pandemic, telemedicine is used in routine oncology care and clinical trials and is associated with cost savings for patients.The growing adoption of this technology provides an opportunity to enhance the study of ultra-rare cancers.Methods: The trial consists of unresectable or metastatic pancreas cancer of any histology in two cohorts: 1) Primary cohort of FGFR2 fusions (n=30) and 2) exploratory cohort of other known activating mutations in FGFR (n=10).Patients are identified from across the United States through Foundation Medicine, Caris Life Sciences, and the Pancreatic Cancer Action Network.Eligible patients will be treated with oral pemigatinib through telemedicine by investigators at The Ohio State University in collaboration with local oncologists for supportive care.This trial uses single-stage phase 2 design with sample size calculations based on an expected overall response rate of $ 33% and ,10% as unfavorable response, at one-sided Type I error of 0.05, 90% power and up to 13% attrition rate. Results: The primary objective is overall response rate.Secondary objectives are overall survival, progression free survival, and duration of response.Exploratory objectives are analysis of correlation of circulating tumor DNA with response to treatment and development of resistance.Conclusions: FGFR kinase inhibitorshave the potential to be an effective targeted therapy in pancreas cancer.Additionally, telemedicine is a novel tool that can aid in the study of ultra-rare cancers and reduce barriers to patient participation in clinical trials.Research Sponsor: Incyte Corporation.TPS718Trials in Progress Poster Session PANOVA-4 (EF-39): Pilot study of tumor treating fields (TTFields) therapy with atezolizumab, gemcitabine (GEM), and nab-paclitaxel (NabP) as firstline (1L) treatment for metastatic pancreatic ductal adenocarcinoma (mPDAC). First Author: Thomas Seufferlein, Universitätsklinikum Ulm, Ulm, Germany Background: TTFields are electric fields that exert physical forces to disrupt cellular processes critical for cancer cell viability and tumor progression. TTFields therapy is noninvasive, locoregional, and is delivered via a portable electric field generator and skin-placed arrays. TTFields therapy has low risk of systemic toxicity and is approved for glioblastoma (and grade 4 glioma in Europe), and pleural mesothelioma. In vitro, TTFields (150 kHz) application decreased pancreatic cancer cell proliferation and clonogenicity; in vivo, TTFields concomitant with chemotherapy (chemo) had greater antitumor effect than chemo alone in orthotopic pancreatic tumors. Co-application of TTFields with immune checkpoint inhibitors (ICIs) significantly decreased tumor volume, increased tumor infiltration and IFN-g production, and did not impede ICI-induced effector memory T-cell production versus in vivo controls. The pilot (phase 2) PANOVA clinical study (NCT01971281) showed safety and feasibility with TTFields therapy plus NabP and GEM in metastatic and locally advanced pancreatic adenocarcinoma (LAPC). The randomized, pivotal (phase 3) PANOVA-3 clinical study (NCT03377491), evaluating TTFields therapy with GEM and NabP in LAPC, is ongoing. Methods: PANOVA-4 (pilot, single-arm clinical study) assesses the safety and efficacy of TTFields therapy (NovoTTF-200T device) concomitant with atezolizumab, GEM, and NabP as 1L treatment for mPDAC. Eligible patients (pts) are $18 years of age and have a new mPDAC diagnosis, measurable abdominal disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1, and no prior systemic PDAC therapy. Atezolizumab (1680 mg, IV infusion) is given before chemo on day 1 of each 28-d cycle, with NabP (125 mg/m 2 IV) and GEM (1000 mg/m 2 IV) given on days 1, 8, and 15. TTFields therapy (150 kHz) is delivered for $18 h/d until disease progression per RECIST v1.1 or loss of clinical benefit. Clinical follow-up occurs every 4 weeks (q4w) with CT scans q8w. Survival is assessed every 3 mo post last on-site visit. The primary endpoint is disease control rate (DCR). Secondary endpoints include overall survival (OS), progression-free survival (PFS), 1-year OS rate, objective response rate, PFS at 6 mo, duration of response, and safety. 76 pts are required to achieve 80% power (1-sided a level 0.05) to detect a 63% DCR vs historical 48% DCR in pts with mPDAC receiving 1L GEM and NabP. Clinical trial information: EUCTR2022-003157-55. Research Sponsor: Novocure, Inc.

48 weeks on treatment, and imaging study will be performed before treatment and every 8 weeks on treatment until 48 weeks. Primary endpoint in the resectable PC cohort is success rate of creating personalized panel using tumor tissue obtained by EUS-FNA/FNB, and that in unresectable PC cohort is rate of concordance of KRAS mutations between tumor tissue and blood samples. Key secondary endpoints in resectable PC cohort are rate of ctDNA positivity for each cancer stage before neoadjuvant chemotherapy and 4 weeks after surgery, and that in unresectable PC cohort is pretreatment ctDNA detection rate for each disease stage. Active enrollment started in December, 2022 and 21 pts with resectable PC and 64 pts with unresectable have been enrolled as of September 2023. Clinical trial information: NCT06043921. Research Sponsor: Invitae. Poster Session Utility of gene expression-based cancer classification in diagnosis of malignant peritoneal mesothelioma (MPeM): Filling in the gaps in standard pathologic work-up for a rare cancer. First Author: Joelle Allam, The University of Texas MD Anderson Cancer Center, Houston, TX Background: Malignant peritoneal mesothelioma (MPeM) is a rare cancer (incidence of 0.12 per 100,000) and an arduous diagnostic challenge, requiring skillful evaluation by expert pathologists. Subjective and experiential immunophenotyping coupled with inattention to this rare entity causes delayed or misdiagnosis and leads to suboptimal treatment and outcomes. Gene-expression-based cancer classification offers an objective molecular assessment of the tissue of origin for cancers with uncertain diagnosis and improves diagnostic accuracy for MPeM compared to standard pathology. Methods: We retrospectively evaluated 23 patients (pts) with cancer of unknown primary (CUP) or uncertain diagnoses, with peritoneal/ retroperitoneal carcinomatosis and reported as malignant mesothelioma using a 92-gene assay (CancerTYPE ID), a validated classifier for predicting tumor types, between January 2013 to December 2016. Pathology was verified by central review. Clinicopathologic data including immunohistochemistry (IHC) was collected using archived pathology specimens and reports. Results: Pts had a median age of 64 years (range: 39 -93) at diagnosis, 57% were females and 74% had biopsy from omentum/peritoneum. Original histopathology was reported as poorly differentiated in 81% and as adenocarcinoma, carcinoma and malignant neoplasm in 10 (43%), 7 (30%) and 6 (27%) of cases, respectively. The number of IHC stains performed ranged between 0 and 28 (median: 10). Key IHC stains are shown in the table. Conclusions: In this cohort of CUP or uncertain diagnoses with a molecular cancer classification of malignant mesothelioma, we found huge variability and critical gaps in pathological work-up. Integration of molecular cancer classification using the 92-gene assay helped resolve this diagnostic uncertainty, further supporting its clinical utility to complement standard pathology. The impact of these findings goes beyond just MPeM and may benefit numerous pts with orphan cancers, who account for nearly 20% of all cancers diagnosed globally. Research Sponsor: None. -world effectiveness and safety of pembrolizumab in mismatch repairdeficient (dMMR) gastrointestinal non-colorectal tumors. First Author: Nieves Martinez Lago, Complexo Hospitalario Universitario de Ferrol, Ferrol, Spain Background: The KEYNOTE-158 trial demonstrated durable clinical efficacy with pembrolizumab in long-term follow-up of previously treated unresectable or metastatic MSI-H/dMMR non-colorectal cancer. Our study, the GAIN study, aims to evaluate effectiveness and safety of pembrolizumab in dMMR Gastrointestinal Non-Colorectal Tumors in real-world clinical practice. Methods: We conducted a multicenter, retrospective, observational study on patients with Mismatch Repair-Deficient (dMMR) Gastrointestinal Non-Colorectal Tumors treated with pembrolizumab in real-world practice at six university hospitals affiliated with the Galician Research Group on Digestive Tumors (GiTUD) in Northwest Spain. Results: Between January 2018 and April 2023, 35 patients were enrolled. The median age was 66 years (range 33-88), with 54.3% being male. Tumor locations included 23 (65.7%) gastroesophageal adenocarcinomas, 3 (8.6%) pancreatic adenocarcinomas, 2 (5.7%) duodenal adenocarcinomas, 2 (5.7%) intrahepatic cholangiocarcinoma, 2 (5.7%) jejune adenocarcinomas, 2 (5.7%) esophageal squamous cell carcinomas, and 1 (2.8%) tumor of unknown origin. 54.3% of tumors were poorly differentiated. The most frequent alteration was the loss of MLH1-PMS2 expression (71.4%). By tumor location, 100% of gastroesophageal, jejune, and unknown origin tumors showed MLH1-PMS2 loss; while 100% of duodenal, pancreatic, and biliary tumors exhibited MSH2-MSH6 loss. All patients received pembrolizumab, with 57.1% having no prior metastatic disease treatment, 80% having ECOG PS0-1, and 31.4% having hepatic metastases. Among 33 evaluable patients, the overall response rate (ORR) was 81.8% (including 30.3% complete response) and the disease control rate (DCR) was 90.9%. Specifically, in gastroesophageal adenocarcinomas, the ORR was 81%, and the DCR was 90.5%. In the overall population, the median progression-free survival (PFS) was 34.76 months (95% CI 5.33 -64.19 months), and the median overall survival (OS) was 39.75 months (95% CI 4.33-75.18 months). Treatment was well-tolerated; only 3 patients discontinued treatment due to nephritis, sarcoidosis-like symptoms, or diarrhea. No treatment-related deaths occurred. Conclusions: Our study underscores the real-world effectiveness of pembrolizumab in patients with dMMR Gastrointestinal Non-Colorectal Tumors. The high ORR, DCR, and favorable safety profile support its use in this challenging patient group, providing valuable real-world evidence for clinical decision-making. Research Sponsor: None.

First Author: Wanqing Chen, Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Background: Gastrointestinal (GI) cancers account for over one-third of cancer-related deaths. We have previously developed GutSeer, a non-invasive assay utilizing cell-free DNA (cfDNA) methylation and fragmentation signatures, to cost-effectively detect and localize five major GI cancers, including colorectal (CC), gastric (GC), liver (LC), esophageal (EC), and pancreatic cancer (PC). Methods: GutSeer was initially developed and validated in a large retrospective cohort of 1844 plasma samples, demonstrating excellent performance with specificity, sensitivity, and tissue of origin (TOO) accuracy at 96.7%, 86.2%, and 82%, respectively. In this study, we conducted a blind, multi-center clinical test for further validation. Participants were recruited from two centers, Beijing (BJ) and Shanghai (SH). Cohort BJ included 42 participants (20 healthy, 22 cancer), and Cohort SH comprised 403 participants (105 healthy, 123 benign, 175 cancer). Over half of the cancer samples in Cohort SH were in early-stage disease (TNM stages I and II). Results: In Cohort BJ, GutSeer showed 100% specificity, 68.2% sensitivity, and 86.7% TOO accuracy. Individual cancer type sensitivities within Cohort BJ were 100% for CC, 57.1% for EC, 75% for GC, 40% for PC, and 100% for LC. In Cohort SH, GutSeer exhibited 94.6% specificity for healthy samples and 86.2% for benign conditions. For cancer samples in Cohort SH, the overall sensitivity achieved 78.9%, with specific sensitivities of 92.3% for CC, 81.0% for EC, 78.4% for GC, 52.9% for PC, and 86.4% for LC. Moreover, GutSeer also efficiently detected early-stage cancers, with stage-wise sensitivities ranging from 64.7% (stage I) to 96.3% (stage IV). TOO accuracy in Cohort SH was 79.0%, with individual cancer types achieving accuracies from 71.7% to 94.7% (72.2% for CC, 71.7% for EC/GC, 94.7% for LC, and 77.8% for PC). Conclusions: GutSeer demonstrates promising potential as a cost-effective, non-invasive test for early detection and localization of major GI cancers. Its consistently high performance in both retrospective and multi-center blind clinical tests implies its potential to revolutionize the screening and diagnosis paradigm for GI cancers. Research Sponsor: None.

Table. Conclusions: In GI cancer patients receiving pembrolizumab monotherapy, severe irAEs are rare. Treatment discontinuation and deaths attributed to pembrolizumab-related irAEs are infrequent, underscoring the safety profile of this therapy in patients with GI cancer. Research Sponsor: None. Phase Ib adaptive study of dasatinib for the prevention of oxaliplatininduced neuropathy in patients with gastrointestinal (GI) cancers receiving FOLFOX chemotherapy with or without bevacizumab. First Author: Anne M. Noonan, The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital, Columbus, OH

Clinical trial information: NCT04164069.Research Sponsor: Pelotonia Intramural Research Program; Noonan_Hu Pelotonia FA18.Durable efficacy of selpercatinib in patients with RET fusion+ solid tumors, with a focus on GI tumors: LIBRETTO-001.First Author: Vivek Subbiah, Sarah Cannon Research Institute, Nashville, TN Background: Selpercatinib, a first-in-class highly selective and potent RET kinase inhibitor with CNS activity, is approved in multiple countries for the treatment of RET-activated cancers.This update includes more patients (pts, n=52) and 16 months (mo) longer follow-up (data cutoff: 13Jan2023) in RET fusion+ solid tumors other than lung/thyroid with a focus on GI histologies.Methods: The phase 1/2 LIBRETTO-001 trial (NCT03157128) enrolled pts with locally advanced/metastatic RET fusion+ solid tumors.51/52ptsreceived the recommended dose of 160 mg orally.The efficacy analysis set consisted of pts enrolled $6 months prior to the cut-off date.Primary endpoint was objective response rate (ORR) by independent review committee (IRC).Secondary endpoints included ORR by investigator (INV), duration of response (DoR), progression-free survival (PFS), and safety.Results: Of the 52 pts with RETactivated solid tumors other than lung or thyroid, 51.9% were female with a median age of 54.0 years.The majority (31/52) of patients had GI RET fusion+ tumor types, with pancreatic (N=13) and colorectal (N=13) as the most common (Table).47pts received prior systemic therapy (median prior lines: 2, range 0-9); 28.8% received $3 lines.In 52 efficacy-evaluable pts, confirmed ORR by IRC was 44.2% (23/52, 95% CI: 30.5, 58.7).ORR by IRC for pts with pancreatic tumors was 53.8% and for colorectal tumors was 30.8%.Clinical benefit (complete response + partial response + stable disease $16 weeks) was observed in 67.3% (35/52) of pts.Median DoR was 37.2 mo (95% CI: 13.3, NE) for overall pts (Table). No new safety signals were identified compared to previous reports. 4 grade 5 AEs were observed (unrelated to treatment by INV), and 2 pts discontinued due to treatment-related AEs per INV. Conclusions: Selpercatinib continued to demonstrate durable antitumor activity and tolerable safety in pts with RET fusion+ cancers across multiple tumor types and fusion partners, including difficult-to-treat GI cancers with poor results in standard-of-care options, such as pancreatic and colorectal. These results emphasize the importance of comprehensive genomic profiling across all tumor types in order to identify actionable oncogenic drivers, including RET fusions. Clinical trial information: NCT03157128. Research Sponsor: Loxo Oncology Inc.

Data cutoff was March 15, 2023. Results: Of 453 pts, 444 received treatment; 40 remain on treatment (ripretinib, 28/223 [13%]; sunitinib, 12/221 [5%]

Eligibility includes advanced GI cancer patients starting a new line of systemic therapy (IO, targeted, chemo or combination) who are not pregnant or s/p organ or bone marrow transplantation.Blood samples are collected at baseline, at the time of imaging, and at least two intermediate time points (~30 days and 60 days post tx initiation).The primary endpoint is to measure the concordance and temporal relationship between disease progression measured by ctDNA compared to RECISTv1.1,clinicalconfirmation,or death.A Cox proportional hazards model will be used to quantify the association between the change in tumor methylation score (TMS; total methylated tumor molecules per 1000 assayed genomic equivalents) and clinical progression.The cohort will be split equally between a training and validation set.Results: Enrollment began in June 2023 and continues.To date, 28 patients with a variety of advanced GI cancers (table) have been enrolled with 37 samples processed.All samples have passed established QC metrics with average turn-around-time from receipt of sample to final report of 9.1 days (95% were ,15 days).TMS ranged from ,120 to .160,000acrossindividualsamples, indicating that the assay can detect a broad range of tumor load in blood.We detected a median of 69 methylated loci per sample (range 4-451).Out of 21 pts, 17 had at least one sample with TMS measured above the noise floor of 120.Conclusions: The Northstar Response assay can consistently detect ctDNA across a variety of advanced GI cancers.Enrollment continues with formal comparison to clinical progression planned.Additional data on the complete training set will be available at the meeting.Research Sponsor: BillionToOne, Inc.Role of circulating tumor DNA in metastatic appendiceal neoplasms: A systematic review.First Author: Moazzam Shahzad, University of South Florida/ Moffitt Cancer Center, Tampa, FL Background: Circulating tumor DNA (ctDNA), tumor DNA fragments detected in blood sourced from primary malignancy, is an emerging non-invasive tool in oncology for screening, diagnosis, and surveillance.Here, we analyze its utility in patients with metastatic appendiceal neoplasms.Methods: Following PRISMA guidelines, PubMed, Cochrane, and Clinicaltrials.govweresearched for 'Appendiceal Neoplasms' AND 'Circulating Tumor DNA'.Four original studies reporting the role of ctDNA in appendiceal cancer were included after screening 195 articles.Results: A total of 196 patients were included in the review.(Table)The total number of collected samples was 209 and 41% were tested positive for ctDNA. Singh et al. 2023 reported eight stage IV appendiceal cancer patients with the median age of 64.5 (45-75) years. 37.5% were tested positive for ctDNA while 37.5% had undetectable ctDNA despite having residual peritoneal disease and 25% had insufficient DNA from tumor specimen. López-Rojo et al. 2020 reported 50% ctDNA positive rate. All included patients had KRAS mutation and received hyperthermic intraperitoneal chemotherapy (HIPEC). On 36.5 months follow-up all the patients were alive but one out of two ctDNA positive patients had a relapse at 39 months follow-up. Kothary et al. 2022 reported 51% ctDNA positivity and 11% had longitudinal ctDNA measurements available which correlated well with their disease course. Zeineddine et al. 2023 collected 160 blood samples from 147 patients. Of 75% with radiographically metastatic disease, 38% had positive ctDNA while out of 25% with no radiographically metastatic disease, 38% had positive ctDNA. The overall survival and progression free survival for ctDNA positive patients was 46.2 months and 60 months, respectively, versus not reached for ctDNA negative patients. When stratified according to tumor grade, the ctDNA detection rate was 22% for welldifferentiated, 39% for moderately differentiated, and 49% for poorly differentiated tumors. Conclusions: The use of ctDNA in metastatic appendiceal tumor is not widespread and detection rates are heterogenous. It was observed more in poorly differentiated appendiceal cancers but further studies are needed to evaluate its utility in clinical practice. Research Sponsor: None.

Conclusions: Findings from this study provide new insights into AA's biological distinctions from CRC and represent a crucial step toward better understanding this rare malignancy.Myeloid cells need further investigation in AA to develop specialized management approaches and improve patient outcomes.Research Sponsor: Conquer Cancer (ASCO); CDA-760412512.Insulin resistance and impaired insulin secretion and gastrointestinal cancer risk in Korean adults: Preliminary results from Korean Genome and Epidemiology study.First Author: Hyemin Jo, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea Background: To date, few studies conducted on the effect of insulin resistance or insulin secretory function on cancer risk in non-diabetic population.This study evaluated whether insulin resistance and/or insulin secretory function affect gastrointestinal cancer risk in the Korean population.Methods: We analyzed data from Korean Genome and Epidemiology Study, Korea Association Resource dataset.It consists of 10,030 participants aged 40-69y observed from 2001 to 2018.The risk of all cancers, and gastrointestinal cancers were assessed.Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and Homeostasis Model Assessment of Beta-cell function (HOMA-b) were used as indicators of insulin resistance and insulin secretory function.Results:In the final dataset, 8,649 individuals without previous history of any cancers were included.During an average follow-up of 15 years, 415 subjects (4.8%) developed cancers.Compared to the low HOMA-IR/high HOMA-b group (reference), diabetic patients had the highest risk of overall cancers, followed by high HOMA-IR/low HOMA-b group (Adjusted hazard ratio[95% confidence interval]: 1.74 [1.11 -2.75] and 1.40 [0.96 -2.06], respectively) Among gastrointestinal cancers, the risk of gastric cancer was higher in the low HOMA-IR/low HOMA-b and high HOMA-IR/high HOMA-b groups (1.92 [1.06 -3.47] and 2.27 [1.26 -4.06], respectively) When further analyzed by HOMA-b stratified by quartiles, the lowest quartile (Q1) showed an increased risk of gastric cancer compared to the highest-quartile (Q4; 1.84 [0.98 -3.46] , p = 0.06) In contrast, no significant results were observed regarding the colorectal cancer risk, when analyzed based on HOMA-IR and HOMA-b.However, when further analyzed by HOMA-IR stratified by quartiles, the highest quartile (Q4) exhibited a significantly elevated colorectal cancer risk compared to the lowest quartile (Q1; 2.14 [1.11 -4.11], P for trend = 0.04).Conclusions: Insulin resistance and impaired insulin secretion function may increase the risk of cancer, but the underlying mechanisms may differ by cancer type.Research Sponsor: None.Gender disparities in the National Institutes of Health funding for gastrointestinal oncology.First Author: Sara Khan, HCA Healthcare/USF Morsani College of Medicine GME, Bayonet Point Hospital, Hudson, FL Background: Traditionally, there has been an under-representation of women in academic fields, thus making them less likely to receive grants.This study examines the trend of funding allocation of R01 grants in Gastrointestinal oncology by the National Institutes of Health with specific focus on the distribution of funding between gender.Methods: The data were retrieved from the NIH RePORTER (Research Portfolio Online Reporting Tools Expenditure) using gastrointestinal oncology-related search terms from 2018-2021.The gender was categorized using Genderize.The number of citations, publications, H-index, and seniority were obtained from Scopus and Web of Science in December 2022.Consumer Price Index was used to adjust funding amount to 2021 equivalent U.S. dollars.Linear regression was used for analysis.Results:A total of 1426 NIHfunded R01 grants amounting to 626.6 million were awarded for gastrointestinal oncology research.Women (n=391; 27.4% [95% CI: 25.1%-29.7%] )receivedfewer grants than men (n=1035; 72.6% [95% CI: 70.3%-74.9%]).From 2018-2021, there was no significant difference in the number of grants awarded among both men (263 to 259, p=0.65) and women (90 to 105, p=0.12).Similarly, there was no significant change in the grant amount (in millions) awarded among men(114.7 to 111.2, p=0.86) and women (39.8 to 47.9, p=0.19). Colorectal cancer accounted for the greatest proportion of grants (n=528; 37.0% [95% CI: 34.5%-39.5%]), amounting to 235.9 million. Of the 481 co-PIs, 405 (84.2% [95% CI: 80.9%-87.5%]) were men and 76 (15.8% [95% CI: 12.5%-19.1%]) were women. Male PIs as compared to female PIs had a higher h-index (52 vs 40, p,0.001), a higher number of publications (160 vs 111, p,0.001), and were cited more (13324 vs 6371, p,0.001). Funding amount was significantly associated with gender (b=0.06, p=0.02), number of publications (b=0.17, p,0.01) and institution (p,0.01). Conclusions: Our analysis shows continued gender disparity as only 27% of total R01 grants towards gastrointestinal oncology were granted to females during the fiscal years of 2018-2021. Thus, a collaborative effort is needed to close the divide and advance gender equality. Research Sponsor: None.

These neoplasms had higher proportions of grade 3 tumors (58% for PT; 32.2% for RT; 50.9% for OT), patients with income .$63,333(38.6% for PT; 38.1% for RT; 36.6% for OT), and patients residing in an area where 6.3%-10.8%didnot graduate from high school (29.8% for PT; 29.7% for RT; 23.8% for OT).From 2004 to 2016, there was a significant increase in the number of tumors of overlapping sites (566 in 2004 to 1848 in 2016) while the number of PT (1580 in 2004 to 1586 in 2016) andRT (726 in 2004RT (726 in to 980 in 2016) )did not change significantly. Conclusions: Among the rare abdominal neoplasms, the number of OT have increased from 2004-2016 while that of PT and RT tumors have remained stable. The histology patterns are consistent with known cancers that involve these regions. Research Sponsor: None.

INSIGHT: A phase 3, randomized, open-label study of ripretinib vs sunitinib in patients with advanced gastrointestinal stromal tumor previously treated with imatinib with KIT exon 11 + 17/18 mutations. First Author: John Raymond Zalcberg, School of Public Health and Preventative Medicine, Monash University, and Alfred Health, Melbourne, Australia Background: Gastrointestinal stromal tumor (GIST) is the most common gastrointestinal sarcoma with approximately 80% of cases driven by KIT mutations. Most patients (pts) with advanced GIST experience disease progression following first-line treatment with imatinib due to KIT secondary resistance mutations occurring most commonly in the ATP-binding pocket (exons 13/14) and/or activation loop (exons 17/18). Sunitinib is approved as second-line therapy for advanced GIST. Ripretinib is a switch-control tyrosine kinase inhibitor approved for pts with GIST who received prior treatment with 3 or more kinase inhibitors, including imatinib. In the phase 3 INTRIGUE study (NCT03673501) in second-line advanced GIST, ripretinib was not superior to sunitinib in terms of progression-free survival (PFS); however, a more favorable safety profile was observed with ripretinib vs sunitinib. 1 Exploratory mutational analysis from INTRIGUE using baseline circulating tumor DNA (ctDNA) demonstrated that pts harboring primary KIT exon 11 mutations with secondary resistance mutations exclusively in KIT exons 17/18 derived PFS benefit with ripretinib vs sunitinib (median, 14.2 vs 1.5 months; HR, 0.22; 95% CI, 0.11 to 0.44; nominal P ,0.0001). 2 Here, we describe a planned phase 3 study for pts with advanced GIST previously treated with imatinib harboring KIT exon 11 + 17/18 mutations. Methods: INSIGHT (NCT05734105) is a phase 3, randomized, open-label study aiming to evaluate the efficacy of ripretinib vs sunitinib in pts with GIST previously treated with imatinib and who harbor KIT exon 11 + 17/18 mutations. Eligible pts must be $18 years old with histologically confirmed GIST and co-occurring KIT exon 11 + 17/18 mutations confirmed by ctDNA analysis. Pts must also have advanced disease with $1 measurable lesion per modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1, radiologic progression on imatinib, and an Eastern Cooperative Oncology Group performance status #2. Key exclusion criteria include a KIT exon 9, 13, or 14 mutation confirmed via ctDNA analysis at screening and prior treatment with another line of therapy in addition to imatinib for advanced GIST. A total of 54 pts will be randomized (2:1) to receive ripretinib 150 mg once daily (QD; continuous) or sunitinib 50 mg QD (4 weeks on/2 weeks off) in 6-week cycles. The primary endpoint is PFS by independent radiologic review (IRR) per mRECIST v1.1; key secondary endpoints are objective response rate by IRR using mRECIST v1.1 and overall survival. Safety and patient-reported outcome measures will also be assessed. Pts randomized to the sunitinib arm may cross over to the ripretinib arm upon disease progression. 1. Bauer S et al. J Clin Oncol. 2022. 2. Bauer S et al. J Clin Oncol. 2023; abstract 397784. Clinical trial information: NCT05734105. Research Sponsor: Deciphera Pharmaceuticals, LLC.

These real-world data from over 10,000 pts with mCRC supplement findings from clinical trials and limited reported RW evidence. While IO demonstrates significant improvement for pts with dMMR/MSI-H, and mOS is similar regardless of whether IO is given in the 1L or later setting, there remains a high unmet need in pMMR/MSS for additional effective treatment options. Research Sponsor: Takeda

Concordance among three programmed death-ligand 1 (PD-L1) scoring methods and their association with clinical outcomes of tislelizumab (TIS) monotherapy in esophageal squamous cell carcinoma (ESCC). First Author: Yongqian Shu, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China Background: Multiple scoring methods and cutoffs have been developed to evaluate tumor PD-L1 expression status in patients with ESCC, and PD-L1 expression level has been associated with the degree of response to anti-programmed cell death protein 1 (PD-1)/PD-L1 therapy. Here, we retrospectively investigated concordance between three PD-L1 scoring methods and their association with clinical outcomes in RATIONALE-302, a phase 3 study of the anti-PD-1 antibody TIS vs investigator-chosen chemotherapy (ICC) as second-line treatment for advanced unresectable/metastatic ESCC (NCT03430843). Methods: Patients enrolled in RATIONALE-302 with evaluable PD-L1 expression by the tumor area positivity (TAP) score (based on visual estimation of positive tumor cells [TCs] and tumorassociated immune cells [ICs] ) using the VENTANA PD-L1 (SP263) assay were categorized at a 10% cutoff. Stained slides from those patients were rescored post hoc using both combined positive score (CPS; based on counting positive TCs and ICs) at cutoff 10 and TC (based on counting positive TCs only) score at a 1% cutoff, thresholds currently used in ESCC for anti-PD-(L)1 therapy. Concordance at these thresholds was investigated. Clinical efficacy (overall survival [OS] ) for PD-L1 subgroups was assessed. Results: Of 512 pts enrolled, 364 had evaluable TAP scores (TIS, n=180; ICC, n=184), of whom 355 had evaluable post-hoc and TC scores (TIS, n=175; ICC, n=180) . TAP score and CPS showed high concordance in terms of overall percentage agreement (OPA; 90% [95% confidence interval (CI): 86, 93]) and Cohen's Kappa (0.79 [95% CI: 0.72, 0.85] ), while TAP and TC scores had lower concordance (OPA: 78% [95% CI: 73, 82]; Cohen's Kappa: 0.56 [95% CI: 0.47, 0.64] ). OS benefit with TIS vs ICC in PD-L1 subgroups defined by TAP, CPS, and TC score cutoffs were generally similar (Table ). Conclusions: OS subgroup analysis showed comparable treatment effect by TAP score at 10% cutoff, CPS at cutoff 10, and TC score at 1% cutoff based on SP263 staining. TAP score and CPS at these cutoffs exhibited substantial concordance. The results indicate that the less time-consuming, visually estimated TAP score and CPS may be interchangeable for clinical measurement of PD-L1 expression in patients with ESCC. Clinical trial information: NCT03430843. Research Sponsor: BeiGene, Ltd.

OS benefit in PD-L1 subgroups by scoring method.

Median OS, Months (95% CI) [event/total] Hazard Ratio (95% CI) Tislelizumab ICC TAP ‡10% 10.0 (8.5, 15

391 Poster Session

Impact of PD-L1 expression on survival in patients with unresectable/ recurrent gastric cancer receiving first-line chemotherapy without immune checkpoint inhibitors. First Author: Hidekazu Hirano, National Cancer Center Hospital, Tokyo, Japan

Background: Although high PD-L1 expression predicts a favorable response of advanced solid tumors to immune checkpoint inhibitors (ICIs), its impact on survival in patients with unresectable/recurrent gastric cancer (GC) has remained unclear. We investigated the prognostic value of PD-L1 expression for survival in unresectable/recurrent GC patients receiving first-line chemotherapy without ICIs. Methods: JCOG1013, a phase 3 randomized trial, demonstrated the addition of docetaxel to cisplatin and S-1 as first-line chemotherapy was of no benefit to patients with unresectable/recurrent GC (N=741) either for overall survival (OS) or progression-free survival (PFS). Tumor specimens prior to chemotherapy were collected for assessing PD-L1 expression for this ancillary study. PD-L1 expression was determined using immunohistochemistry (Dako, and used to derive the PD-L1 combined positive score (CPS) and PD-L1 tumor proportion score (TPS). As with the CheckMate 649 study, the cutoff values for PD-L1 CPS and PD-L1 TPS were set at 5 and 1%, respectively. Multivariable analyses were performed using Cox proportional hazard models to evaluate the prognostic significance of PD-L1 CPS and PD-L1 TPS as predictors of OS and PFS. All p values were 2-sided; values ,0.05 were considered statistically significant. Results: We analyzed 427 patients with unresectable/recurrent GC. The prevalence of PD-L1 CPS$5, and PD-L1 TPS$1% was 33% and 24%, respectively. There was no significant difference in OS and PFS between the PD-L1 CPS $5 group and the PD-L1 CPS ,5 group (Table ). The PD-L1 TPS $1% group had superior OS and PFS compared to the PD-L1 TPS ,1% group (Table ). In multivariable analyses for OS, PD-L1 TPS $1% was a significant favorable prognostic factor (hazard ratio (HR) = 0.64 [95% CI: 0.50-0.83], p,0.001), but PD-L1 CPS$5 was not (HR = 0.82 [95% CI: 0.65-1.02], p = 0.073). In multivariable analyses for PFS, PD-L1 TPS $1% was a significant favorable prognostic factor (HR = 0.67 [95% CI: 0.52-0.84], p,0.001), but PD-L1 CPS$5 was not (HR = 0.83 [95% CI: 0.67-1.03], p = 0.090).

Conclusions: PD-L1 TPS$1% is significantly correlated with longer OS and PFS in patients with unresectable/recurrent GC receiving first-line chemotherapy without ICIs. PD-L1 TPS should be considered as a stratification factor in randomized clinical trials for unresectable/recurrent GC. Clinical trial information: UMIN000007652. Research Sponsor: None.

Efficacy based on PD-L1 expression.

PD-L1 CPS PD-L1 TPS

,5 (N=285) $5 (N=142) < 1% (N=324) $1% (N=103) OS Median, mo (95% CI) HR (95% CI), log-rank p 15.4 (13.7-17.3) -15.2 (12.5-17.6) 0.89 (0.71-1.11), 0.299 14.6 (13.4-16.5 ) -16.1 (14.8-21.1) 0.74 (0.58-0.95), 0.016 PFS Median, mo (95% CI) HR (95% CI), log-rank p 7.2 (5.8-6.5) -7.3 (5.8-9.1) 0.94 (0.76-1.16), 0.557 7.0 (6.2-7.5) -7.9 (6.2-7.9) 0.76 (0.61-0.96), 0.023

392 Poster Session

Oncogenic aberrations in primary gastric cancer tumors to predict metachronous peritoneal metastasis. First Author: Joseph J Zhao, Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore Background: Peritoneal metastases (PM) in gastric cancer (GC) portend a poor prognosis. Yet, there are a paucity of data on underlying genomic alterations predictive of GCPM. Methods: Two-hundred and nine patients who underwent primary tumor (PT) surgical resection were included in the prospective cohort. Whole exome sequencing (WES) of these resected PT GC specimens (average coverage 129X for tumor samples, 70X coverage for matched normal/blood controls) were undertaken. Participants were followed-up longitudinally for peritoneal metastases. Results: Fifty-one (51/209, 24.4%) patients developed PM after a median follow-up duration of 87.0 months and had poorer survival outcomes compared to patients without metastasis (log-rank, p,0.001). Patients with bulkier and more advanced tumors were at increased hazard of PM (T-stage and N-stage stratified analysis, log-rank, p,0.0001). Consistent with known clinical outcomes, The Cancer Genome Atlas (TCGA) genomically stable (GS) subtype (log-rank, p=0.0059) and mesenchymal subtype GC were associated with a higher proclivity for peritoneal organotropism (log-rank, p=0.020). Among patients who developed PM, TP53 was the most commonly altered driver mutation (25/51, 49.0%), followed by ARID1A (9/51, 17.6%), CDH1 (8/51, 15.7%), PIK3CA (6/51, 11.8%). Comparing the PTs of patients with PM against those PTs without PM, ELF3, CDH1 and PIGR were significantly associated with PM (all adjusted p,0.05). Amongst TCGA GS tumors, ARID1A mutations (p=0.018) were significantly associated with PM compared to patients with GS tumors with no metastasis. CDH1 mutations were found to significantly co-occur with PIGR and RHOA mutations and was mutually exclusive to TP53. ARID1A mutations were also found to significantly co-occur with multiple other mutations such as PTEN, PIK3CA, ERBB2, and KRAS. Conclusions: CDH1, PIGR, ELF3 mutations in primary GC tumors were found to be significantly associated with metachronous PM.

Preoperative weight loss program for hepatocellular carcinoma patients with high body mass index in hepatectomy. First Author: Yu Saito, Department of Surgery, Tokushima University, Tokushima, Japan Background: This study aimed to investigate the usefulness of a weight-loss program (WLP) in patients with a high body mass index (BMI) prior to liver resection (Hx) for hepatocellular carcinoma (HCC). Methods: Among 445 patients with HCC who underwent initial Hx between 2000 and 2020, 19 with a high BMI ($25.0) were enrolled in our WLP since 2014. For calorie restriction, the amount of energy consumed was calculated as the standard body weight (SBW) kg 3 20-25 kcal/day. Protein mass was calculated as SBW kg 3 1.0-1.2 g/day to maintain skeletal muscle mass. Patients also performed both aerobic and resistance exercises. The before-and-after changes were compared, and the effect of WLP on the short-and long-term results was investigated.

567 Poster Session

Association of congestive heart failure (CHF) with incidence rates of enteric infections and gram-negative sepsis (GNS) in patients with hepatopancreatico-biliary cancers (HPBCs). First Author: Himil Mahadevia, University of Missouri Kansas City, Kansas City, MO Background: ChronicCHF leads to volume overload and can cause bowel wall edema. This may compromise local immune defense and promote increased translocation of gut bacteria into the blood.HPBCs can cause biliary tract obstruction which is also associated with bacteremia. Additionally, cancer treatments are associated with an increased risk of clostridium difficile infection (CDI), regardless of antibiotic exposure. While associations between cancer and increased infection rates are well-established, we questioned whether concomitant CHF increases this risk further in the HPBC population. We therefore investigated whether concomitant CHF and HPBC influenced CDI, other infectious gastroenteritis (IGE), GNS rates or all-cause-hospital mortality. Methods: A retrospective study was conducted by obtaining patients with HPBC through the application of specific ICD 10 codes from the National Inpatient Sample 2020, a large publicly available database of inpatient hospital stays incorporating data from hospitals across 48 U.S. states. Among this cohort, patients with chronic CHF were further identified by applying all CHF-specific ICD 10 codes. All patients with HPBC were divided into two groups, one with CHF (group A) and the other without CHF (group B). Outcomes were compared between the two groups using multivariate regression analysis (MVRA) adjusting for demographic factors, hospitalspecific characteristics like location, bed size, etc., comorbidities including obesity, diabetes, hypertension, prior cardiovascular events, HIV, CKD, OSA, etc., prior coronary intervention/surgery as well as alcohol, smoking or substance use. Results: 211,790 patients were identified with HPBC. 40.55% were female. 18,955 patients (9.95%) were found to have chronic CHF. The incidence of GNS was higher in group A compared to group B in the MVRA (Adjusted (Ad) OR: 1.4, CI 1.07-1.95, p=0.015). However, there was no difference in the incidence rate of CDI between groups A and B (Ad OR: 1.0, CI 0.71-1.50, p=0.86). Similarly, the two groups had no difference in other IGE (Ad OR: 1.0, CI 0.71-1.37, p=0.96). All-cause hospital mortality was slightly higher in group A than group B but failed to reach statistical significance (Ad OR: 1.1, CI: 0.99-1.29, p=0.069). Conclusions: GNS was more common in patients with HPBC who also had comorbid chronic CHF. Future investigations may focus on the effect of increased GNS on outcomes beyond hospitalization, correlation between the severity of CHF and GNS as well as primary site of HPBC and infection risk. Based on this signal-finding analysis, it is postulated that early interdisciplinary collaboration between oncology and cardio-oncology/cardiology may have special significance in the management of patients with chronic CHF and HPBCs, the latter of which already carries a dismal prognosis. Research Sponsor: None.

568 Poster Session

A novel image-guided laparoscopic liver resection with integrated fluorescent imaging and artificial intelligence: A preliminary study. First Author: Yoshihiko Tashiro, Showa University, Shinagawa-Ku, Japan

Background: Technology innovations improve surgical techniques. ICG fluorescence imaging is beneficial for real time navigation tool during surgery and enables accurate surgery. Recently, the prediction of anatomical structures by artificial intelligence (AI) is expected to support surgeons as navigation tool. We developed a visual-support AI system to perform the laparoscopic liver resection (LLR) using ICG fluorescence imaging and AI technology. Methods: Procedure: ICG fluorescence imaging was used for liver mapping and securing surgical margin. AI model development and evaluation: Over 430 images extracted from 13 videos of LLR for hepatocellular carcinoma and colorectal liver metastasis was used to develop and evaluate the AI algorithm at Anaut Inc. The annotation was performed on video frames capturing a LLR performed by 2 surgeons for hepatic vein and Glisson sheath. The performance of AI on unlearned LH videos was evaluated quantitatively using Intersection-Over-Union (IOU) and Dice coefficients, and qualitatively on a five-point scale (from 1 to 5) by 10 hepato-biliary-pancreatic surgeons using 35 randomly extracted still images from the analyzed videos. Results: ICG fluorescence imaging could visualize the demarcation line and clarified the boundaries of the liver transected surface. The hepatic veins and Glisson sheath were appeared in the parenchymal transection plane during segmentectomy and securing surgical margin, and this AI system enabled to recognize and display these vascular structures through color-coding under bleeding and ICG fluorescent imaging without visual discrepancies.

The AI model accurately recognized vascular structures of any size (IoU=0.33, Dice=0.44) in real-time (,0.12 s) In the qualitative evaluation by surgeons, the mean sensitivity score was 4.10 6 0.92 (range 3.61-4.76). Additionally, this AI system also recognized vascular structures during robot-assisted liver resection. Conclusions: This is the first study demonstrating that AI can precisely identify vascular structures during LLR. Novel image-guided LLR using ICG fluorescent imaging and artificial intelligence is expected to provide safer and more accurate LLR, thereby contributing to reduce complications and improve survival rates. Research Sponsor: None.

140s HEPATOBILIARY CANCER

Oral Abstract Session

[ 177 Lu]Lu-DOTA-TATE in newly diagnosed patients with advanced grade 2 and grade 3, well-differentiated gastroenteropancreatic neuroendocrine tumors: Primary analysis of the phase 3 randomized NETTER-2 study.

First Author: Simron Singh, Division of Medical Oncology, Sunnybrook Odette Cancer Center, University of Toronto, Toronto, ON, Canada

Assessment of hematological toxicity in patients with advanced neuroendocrine tumors and extensive/innumerable bone metastases undergoing lutetium-177 DOTATATE treatment. First Author: Osama M Mosalem, Mayo Clinic Florida, Jacksonville, FL Background: The introduction of peptide receptor radionuclide therapy (PRRT) using Lutetium-177 ( 177 Lu) DOTATATE has led to a paradigm shift in the treatment of neuroendocrine tumors (NETs). Hematological toxicity is a well-recognized adverse effect (AE) of 177 Lu DOTATATE. Most cytopenias are transient, with an estimated incidence of 10-25%, typically mild to moderate in severity (grade G1-2). The most dreaded AE of PRRT is therapy-related myeloid neoplasm (t-MN), with an estimated 2-8% incidence and a higher incidence reported in patients who also received prior chemotherapy. We sought to evaluate the hematological safety of 177 Lu PRRT in the setting of NETs with extensive (i.e., innumerable) bone metastases. Methods: We retrospectively reviewed the medical records of all Mayo Clinic patients (pts) with extensive/innumerable osseous metastases, defined as .50% skeletal involvement by positron emission tomography (PET) DOTATATE, who were treated with 177 Lu DOTATATE. Pts characteristics and laboratory results were collected before, during, and after 177 Lu DOTATATE treatment. Hematotoxicity was graded according to the NCI-CTCAE v5. Results: Out of 27 pts, 13(48%) developed cytopenia(s) of any grade after treatment with one or more cycles of 177 Lu DOTATATE. In total, there were 13(48%) pts with anemia, 13(48%) with thrombocytopenia, and 6(22%) with neutropenia. Six (22%) pts had severe hematological toxicity (G3-4). Twelve months post-PRRT, 7(26%) pts continued to experience cytopenia(s) of any grade, of whom 4(15%) had G3-4 hematotoxicity. One pt developed t-MN, and two pts had myelophthisis on bone marrow biopsy from infiltrating NET. 16(59%) pts received cytotoxic chemotherapy before PRRT, and 7(25.9%) developed subsequent cytopenia(s). Overall, 15(55%) pts completed four cycles, while 3 pts didn't complete four cycles of 177 Lu DOTATATE due to hematotoxicity. Conclusions: Pts with advanced NETs and extensive/innumerable bone metastases treated with PRRT could be at higher risk for myelosuppression than historical controls. Our study highlights the importance of carefully monitoring and assessing hematological parameters in pts being considered for 177 Lu DOTATATE with extensive/ innumerable bone metastasis. Research Sponsor: None.

NCI-CTCAE grading of hematological toxicity among patients with prolonged toxicity (i.e., ‡ 12 months).

Patient Anemia (grade)

Bone Marrow Evaluation

593 Poster Session

Real-world 177 Lu-DOTATATE peptide receptor radionuclide therapy: Treatment outcomes with dosing variations and in non-midgut neuroendocrine tumors. First Author: Hwan Lee, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA Background: Peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE has been used for neuroendocrine tumors (NETs) since its approval in the United States based on demonstrated progression-free survival benefit in grade 1-2 midgut NETs. The recommended dosing is 7.4 GBq (200 mCi) every 8 weeks for 4 doses in total. We examined the post-PRRT outcomes with dosing variations and in patients with nonmidgut NETs. Methods: The medical records of 108 PRRT-naïve NET patients who received at least one cycle of PRRT at a single academic institution were reviewed. Among the patients with Ki-67 index # 20%, progression-free survival (PFS) and overall survival (OS) were compared between midgut and non-midgut NETs. Among the patients who did not develop disease progression or mortality during the treatment course, PFS and OS were compared based on dosing variations. Dosing variations were defined as "reduced" (50% of 7.4 GBq/cycle), "delayed" (.12 weeks between cycles), or "fewer" (,4 cycles) doses. Kaplan-Meier survival analysis with log-rank test was used for statistical analysis. Results:

595 Poster Session

Advances in the treatment of gastroenteropancreatic poorly differentiated neuroendocrine carcinoma at our hospital. First Author: Shinichi Nishina, Department of Medical Oncology, Kurashiki Central Hospital, Okayama, Japan Background: Overall survival after first-line chemotherapy for metastatic or recurrent gastroenteropancreatic poorly differentiated neuroendocrine carcinoma (GEP-NEC) is reported to be less than 1 year. Platinum drugs in combination with etoposide or irinotecan have been used as first-line chemotherapy for GEP-NEC patients, but no standard treatment has been established for second-line and subsequent chemotherapy. Recently, however, we have seen patients with a good prognosis after treatment based on comprehensive cancer genomic profiling (CGP). We retrospectively reviewed GEP-NEC patients treated with chemotherapy. Methods: Patient background, treatment regimen, overall survival, and toxicity were evaluated in 20 GEP-NEC patients who started first-line platinum combination chemotherapy at our hospital between October 2016 and September 2022. Results: Median age was 71 (48 to 81) years, 16 were male, and primary sites were esophagus in 2 patients, stomach in 7 patients, small intestine in 2 patients, large intestine in 6 patients, and pancreas in 3 patients. Five patients had an adenocarcinoma component. Stage III, IV, and recurrence were observed in 2, 16, and 2 patients, respectively. Progression-free survival and overall survival after first-line chemotherapy were 4.0 (2.3 to 7.0) and 8.1 (4.7 to 17.0) months, respectively. Grade 3 or higher toxicity was observed in 13 patients. No differences in overall survival were observed in chemotherapy regimen including etoposide or irinotecan and cisplatin or carboplatin. Patients who underwent CGP had significantly longer survival. After second-line chemotherapy, a regimen containing irinotecan, 5-FU, paclitaxel, ramucirumab, and nivolumab was used, and overall survival was 5.2 (1.8 to NA) months. There were 4 of 20 patients who survived for more than 1000 days after first-line chemotherapy. Durable responses were observed in colonic NEC patients harboring the POLE P286R mutation treated with nivolumab and in those harboring the BRAF V600E mutation treated with cetuximab and encorafenib. Conclusions: Overall survival of GEP-NEC patients treated with platinum combination chemotherapy was very poor at only 8 months. However, in some cases, long-term survival has been achieved with molecular targeted therapy based on CGP results. Research Sponsor: None.

General Session

Addition of metastasis-directed therapy to standard-of-care systemic therapy for oligometastatic pancreatic ductal adenocarcinoma (EXTEND): Results of a multicenter, randomized phase II trial. First Author: Ethan B. Ludmir, Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX Background: Standard treatment of oligometastatic pancreatic ductal adenocarcinoma (PDAC) consists of multi-agent chemotherapy, although outcomes remain poor. We tested the hypothesis that the addition of comprehensive metastasis-directed therapy (MDT) to standard-of-care systemic therapy would improve progression-free survival (PFS) compared with systemic therapy alone. Methods: The External Beam Radiation to Eliminate Nominal Metastatic Disease (EXTEND) trial is a multicenter phase II basket trial randomizing patients with # 5 solid tumor metastases 1:1 to MDT plus systemic therapy versus systemic therapy alone. Each histology-specific basket was pre-specified and independently powered for the primary endpoint of PFS; here we present results of the pancreatic cancer basket. Progression was defined by radiographic criteria (RECIST v1.1), clinical events, or death. Patients were stratified at randomization by number of metastases (1-2 vs 3-5), number of prior lines of systemic therapy (0-1 vs 2+), and cancer antigen 19-9 (CA-19-9) level (,90U/ml vs $90U/ml

The economic impact of short-term imaging with metastatic pancreatic ductal adenocarcinoma. First Author: Abbey Bayless, University of Arizona College of Medicine, Tucson, AZ Background: Although modern cancer treatment has significantly improved overall survival, this comes with a high financial cost. Based on an NIH report on Financial Burden of Cancer Care, treating pancreatic adenocarcinoma (PDAC) costs $108K, $18K, and $125K for initial treatment, during follow-up, and in last year of life, respectively.

During the course of treatment, patients will visit the hospital for acute symptoms for which cross-sectional imaging is obtained within 45 days of subsequent scheduled follow-up imaging. This presents an opportunity for cost saving if data could be collected to identify an algorithm to avoid unnecessary duplication of imaging in a short interval.

The purpose of this pilot study is to evaluate tumor growth trajectory within this short time span of 45 days to guide future trials to clarify the circumstances for which a subsequent follow up study is necessary. Methods: We retrospectively identified patients from our tumor registry from 2016 to 2019 who were diagnosed with metastatic PDAC (mPDAC). Subjects were included for analysis if they met the following criteria: 1) diagnosed with mPDAC; 2) had at least 2 CT abdomen/pelvis (CTAP) within 45 days of each other with one of the studies being obtained in the emergency department; and 3) had at least 1-3 measurable lesions as defined by RECIST 1.1 criteria. Tumor dimension was measured on axial images with the largest cross-section. For our primary outcome we used paired t-tests to evaluate the difference in mean size of all lesions (primary and metastatic). We also performed sub-group analyses comparing mean size of primary and metastatic lesions separately. An alpha level of 0.05 was used to determine statistical significance. Results: We screened 383 subjects from the tumor registry and identified 28 subjects suitable for our study. 18 subjects were female and 10 were male. We identified 69 target lesions, 23 of which were primary and 46 were metastatic. The mean sum of the largest dimension of target lesions was 2.82 cm on the initial study and 3.23 on the latter study (p,0.001). The mean sum of the largest dimension of the primary lesion was 3.62 cm on the initial study and 3.89 on the latter study (p=0.01). For metastatic lesions, the initial sum was 2.38 cm while the latter was 2.85 (p,0.001).

Conclusions: Our finding of increase in tumor size in 45 days for mPDAC suggests that mPDAC is aggressive and can grow even in short time span. This suggests that if progression is identified on a study obtained within 45 days of scheduled follow-up, the follow-up study could be cancelled to avoid added cost to the patient. However, if the earlier study is stable or shows response, the scheduled follow-up may still be necessary to demonstrate continued stability/response. Research Sponsor: None.

644 Poster Session

Impact of facility volume on outcomes in patients with pancreatic cancer treated with radiotherapy. ) showed improved survival compared to gemcitabine monotherapy for patients with metastatic pancreatic cancer and has become the one of the standard regimens. Despite of its clinical benefit, FOLFIRNIOX needs continuous infusion of 5-FU for 46 hours, which impairs patient's quality of life. In other gastrointestinal cancer, infusion pump free regimens, in which oral 5-FU drug replace the continuous infusion of 5-FU, have developed as alternative regimen by its convenience. Therefore, we planned to develop new combination chemotherapy with oxaliplatin, irinotecan and S-1 (OX-IRIS) for metastataic pancreatic cancer. Methods: HGCSG1803 study has conducted as a multicenter, non-randomized, single arm, phase II study in Japan. The chemotherapynaïve patients with metastatic pancreatic cancer were eligible. S-1 (40 mg/m 2 ) orally intake twice daily for 14-day followed by a 14-day rest, and intravenous 65 mg/m 2 of L-OHP and 100 mg/m 2 of IRI on day 1 and day 15 every four weeks were continued until disease progression or unacceptable toxicity. In the median follow-up time was 13.7 months, median progression free survival and overall survival were 4.3 months (95%CI 2.5-6.2 months) and 11.1 months (95%CI 7.2-14.9 months), respectively. Four patients discontinued protocol therapy due to adverse events (AE) without disease progression. Grade 3 or higher AE that occurred in more than 5% of patients were leucopenia (21%), hypokalemia (21%), neutropenia (18%), anemia (15%), hyponatremia (15%), ALT elevation (10%), anorexia (8%), nausea (5%), and febrile neutropenia (5%). One patient died due to protocol therapy (drug induced pneumonitis).

Conclusions: OX-IRIS showed high response rate with manageable safety, and the primary endpoint was met. This new triplet regimen could be a useful first line treatment option for patients with metastatic pancreatic cancer. Clinical trial information: jRCTs011190008. Research Sponsor: None.

648 Poster Session

A phase I/II study of antroquinonol in combination with nab-paclitaxel and gemcitabine for patients with metastatic pancreatic cancer. First Author: Yan-Shen Shan, Distinguished Professor and Attending Surgeon, College of Medicine, NCKU and NCKUH, Tainan City, Taiwan Background: The survival of metastatic pancreatic cancer (mPC) is still disappointing though advancement in recent regimens. Antroquinonol, a new chemical entity, has been proposed for the treatment of neoplasms. In this phase I/II trial, we investigated the dose and efficacy of antroquinonol combined with gemcitabine and nab-paclitaxel (Gem/Nab-P) on mPC patients. Methods: Patients with chemo-naive, metastatic PDAC were enrolled. In the phase I, run-in drug-drug interaction (DDI) and dose escalation in a 3 + 3 designed to determine the maximal tolerated dose (MTD) of antroquinonol for phase II study. Gem/Nab-P (gemcitabine 1000 mg/m 2 and nab-paclitaxel 125 mg/m 2 on days 1, 8, and 15 every 4 weeks) was given from cycle 0 in phase I. The dose of antroquinonol was escalated from 200mg orally three times a day since the first cycle of Gem/Nab-P. The primary end points were median PFS and 6-month PFS rate. This trial is registered at ClinicalTrials.gov: NCT03310632. Results: In the phase I study of 15 patients, the MTD of antroquinonol was 300mg tid. In the phase II study of 40 patients, the median PFS was 5.3 (95% CI: 3.7-7.5) months and 6-month PFS rate was 40% (95% CI: 21%-57%), whereas median OS was 12.6 (95% CI: 8.8-15.8) months and12-month OS rate was 59.9% (95% CI: 37.8%-76.4%), respectively. The adverse events including hematological and non-hematological classes were decreased in the antroquinonol plus Gem/Nab-P, the GI discomforts were increased but manageable. Conclusions: In this phase I/II trial, antroquinonol plus Gem/Nab-P showed good efficacy in survival and less adverse events than a first-line strategy of Gem/Nab-P for mPC patients. Clinical trial information: NCT03310632. Research Sponsor: Golden Biotechnology Corp.

Summary of adverse events in mPC with antroquinonol plus Gem/Nab-P or Gem/Nab-P treatment.

Adverse

650 Poster Session

Safety and efficacy of chemotherapy for patients with unresectable pancreatic cancer concomitant with collagen disease: A multicenter retrospective observational study. First Author: Hiroyuki Asama, Department of Gastroenterology, Fukushima Medical University, Fukushima-Shi, Japan Background: In patients with collagen disease, such as rheumatoid arthritis, steroids and immunomodulators are often used for treatment. These treatments increase the risk of adverse events, including infections; thus, cancer patients with collagen disease are often excluded from clinical trials of chemotherapy for cancer. Therefore, evidence is lacking regarding the safety and efficacy of chemotherapy for pancreatic cancer concomitant with collagen diseases. Methods: This was a multicenter, retrospective study in Japan. Patients who started first-line chemotherapy or chemoradiotherapy for unresectable pancreatic cancer between January 2015 and December 2019 and had concurrent collagen diseases were included. We evaluated adverse events (AEs), discontinuation of anticancer treatment due to AEs, progression-free survival (PFS) and overall survival (OS). Results: A total of 52 patients were enrolled from 20 institutions in Japan, and a total of 101 regimens were administered. Concomitant collagen diseases included rheumatoid arthritis (n=35), systemic lupus erythematosus (n=5), Sjögren's syndrome (n=4), vasculitis syndrome (n=3), dermatomyositis/polymyositis (n=2), polymyalgia rheumatica (n=1), systemic sclerosis (n=1), and Behçet's disease (n=1). The most common regimens for pancreatic cancer were gemcitabine/nab-paclitaxel (GnP, n=40), S-1 monotherapy (n=18), gemcitabine monotherapy (n=15), modified FOLFIR-INOX (n=10), S-1 concurrent radiotherapy (n=5), and FOLFOX (n=4). Treatment discontinuation due to AEs occurred in 21 regimens (20.8%). The most common causes of discontinuation were thrombosis in 4 regimens, interstitial lung disease (ILD) in 3 regimens, and fatigue in 3 regimens. Infection as an adverse event was observed in 7 regimens (6.9%). By regimen, GnP had the highest discontinuation rate for adverse events of 37.5% and an incidence of ILD of 15.0%. The median PFS was 5.6 months in first-line therapy, and the median OS was 11.1 months. By regimen, the median PFS (5.

674 Poster Session

Comparison between different therapeutic sequences in patients affected by metastatic pancreatic ductal adenocarcinoma. First Author: Andrea Pretta, Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy Background: The first-line treatment of metastatic pancreatic cancer involves different therapeutic regimens, among them, mFOLFIRINOX and gemcitabine-nabpaclitaxel. However, it remains to be clarified which sequence might correlate with better outcomes. The aim of our work was to evaluate which sequence leads to better overall survival in this setting. Methods: We retrospectively collected data from 358 patients affected by stage IV pancreatic ductal adenocarcinoma from 3 different Italian Institutions. Patients received mFOLFIRINOX or gemcitabine plus nabpaclitaxel as first-line chemotherapy, followed by a second-line non-cross-resistant chemotherapy (gemcitabine or fluoropyrimidine-based combinations). Survival distribution was assessed by Kaplan-Meier curves. The primary endpoint was median overall survival. Statistical analysis was performed with MedCalc package. Results: The median age was 66 (6 9), 195 (54,4%) were male and 163 (45,6%) were female. 292 (81,5%) patients start gemcitabine plus nabpaclitaxel as first line treatment, while 66 (18,5%) patients start mFOLFIRINOX first-line therapy. No statistically significant differences in terms of mOS were observed between the two mFOLFIRINOX and gemcitabine-nabpaclitaxel groups: 16 versus 15 months, respectively, p = 0,2). No significant differences were found in terms of mPFS either: 7 versus 8 months, respectively, p = 0,3). Conclusions: The results of our retrospective study showed no statistically significant survival advantage between the sequences starting with mFOLFIRINOX or with gemcitabine-nabpaclitaxel. Further studies will be necessary to establish the effectiveness of new therapeutic schemes to be introduced into clinical practice in order to define a better therapeutic algorithm. Research Sponsor: None.

675 Poster Session

Precision Promise (PrP) Bayesian platform trial for metastatic pancreatic cancer (mPDAC): Results of the first experimental arm, SM-88 as second line therapy. First Author: Paul Eliezer Oberstein, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY Background: PrP is a phase 3 Bayesian adaptive platform trial for efficiently testing multiple arms against a common control. Its design is what FDA calls a Complex Innovative Design (www.fda.gov/media/130897/download). Experimental arms in stage 1 are adaptively randomized against other arms. The maximum size of an arm's stage 1 is 100 subjects. Strong efficacy in stage 1 leads to a fixed randomization stage 2. Stages 1 and 2 are combined for the arm's final analysis and, if positive, would be submitted for drug registration. SM-88 (D,L-alphametyrosine) is a dysfunctional, racemic tyrosine mixture designed to interrupt PDAC cellular metabolism and induce oxidative stress. Methoxsalen, phenytoin and sirolimus are added to SM-88 to potentially enhance oxidative stress, and form a 4-drug oral regimen. SM-88 was selected for testing in 2nd line mPDAC using the PrP platform. Methods: Primary endpoint overall survival (OS) is analyzed based on modified intention to treat (mITT). Randomization is 7:3 to experimental and control arms. Efficacy is defined by OS hazard ratio (HR, experimental vs control). All statistical measures in PrP are Bayesian. Superiority (HR , 1) is assessed monthly and is claimed should the Bayesian probability of benefit be $ 98%. Futility analyses occur monthly once 50 subjects have accrued to the arm. Accrual ends for futility if Bayesian predictive power (PP) of eventual success in PrP is , 20% for all the arm's signatures. Follow-up continues for 12 months after arm accrual stops. PrP experimental arm designs are flexible: an arm's protocol appendix can supersede the master protocol. However, type I error is controlled at , 0.025, as shown by simulation. Results: SM-88 entered PrP in Apr 2020. As the first experimental arm in PrP, it was randomized 7:3 against control arms. Pooled controls for SM-88 were gemcitabine/nab-paclitaxel and mFOLFIRINOX at standard doses, since neither therapy was a backbone for SM-88. Between 4/2020 -10/2021, 142 subjects were screened, 73 subjects started therapy and are included in the mITT cohort. 55 subjects were enrolled in the SM-88 arm and 18 in control arms.

PANCREATIC CANCER 167s

Adjuvant radiotherapy after curative resection of hepatocellular carcinoma with narrow margin (£1 cm): A phase 2, multicenter, randomized controlled trial. First Author: Kuang Ming, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China Background: RAISE is a multicenter, randomized, open-label, parallel-group phase 2 trial, aiming to assess the efficacy and safety of intensity modulated radiation therapy (IMRT) compared with active surveillance in hepatocellular carcinoma (HCC) patients with narrow margin (# 1 cm) following curative resection. Methods: HCC patients with narrow margin were randomly assigned in a 1:1 ratio to receive either IMRT (Surgery-IMRT group) or active surveillance (Surgery group) after hepatectomy. Randomized stratification factors include tumor size (# 5 vs. . 5 cm) and microvascular invasion (presence vs. absence). In the Surgery-IMRT group, patients received IMRT within 1-3 months after surgical resection. The prescription dose was planned at 50-60 gray in 25-30 fractions over 5-6 weeks. The primary endpoint was recurrence free survival (RFS). The secondary endpoints were safety and overall survival (OS). The planned sample size was 148 patients in total to obtain an improvement in the 2-year RFS rate from 45% to 65%, to detect a hazard ratio (HR) of 0.54, with a one-sided alpha of 5% and 80% power. Results: Between January 15, 2019, and September 15, 2023, 148 patients from 6 hospitals in China were randomized: 74 patients were allocated to the Surgery-IMRT group and 74 to the Surgery group. The median follow-up duration was 27.4 months (95% confidence interval [CI] 23.2-29.2 months). The 2-year RFS was 78.37% (95% CI 64.35%-87.40%) for the Surgery-IMRT group and 57.43% (95% CI 43.25%-69.28%) for the Surgery group (P=0.028). The median OS was not reached for the two groups. The following radiotherapy-related grade 3-4 adverse events were 3 thrombocytopenia, 3 neutropenia, and 1 hemoglobin decreased. Conclusions: In conclusion, this trial showed that the adjuvant IMRT following curative resection can bring survival benefits of RFS for HCC patients with narrow margin. Clinical trial information: NCT03732105. Research Sponsor: None.

723 Poster Session

Income and its impact on adenomatous neoplasms outcomes: An analysis of the National Cancer Database. First Author: Eric G. Nielsen, Creighton University School of Medicine, Omaha, NE Background: Adenomatous neoplasmsof the small intestine are rare benign tumors but are occurring with increasing incidence. They exhibit a slight male predominance, with a median age of diagnosis in the 6th decade of life. The duodenum is the most frequent location of onset. Proposed environmental risk factors include high animal fat and protein diets, intestinal flora composition, and hereditary factors. Additionally, intestinal diseases, such as Crohn's disease or Lynch syndrome, predispose individuals to develop small intestine adenomatous neoplasms. Despite this knowledge, no National Cancer Database (NCDB) research exists analyzing the association between survivability and income. Therefore, the objective of this study is to investigate overall survival rates among individuals with adenomatous neoplasms based on income levels. Methods: The NCDB was used to identify patients diagnosed with small intestine adenomatous neoplasms from 2004 to 2019 using the histology code 8140 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square tests were performed, and data were analyzed using SPSS version 27. Statistical significance was set at a = 0.05. Results: Of 19,582 patients included in the sample, 6,326 (30.8%) were from the highest income bracket, defined as annual income greater than $46,000, while 3,629 (24.4%) were from low-income brackets, defined as earnings less than $30,000. High-income patients experienced longer mean overall survival (58.5 months) compared to middle (49.7 months) and low (46.7 months) income patients (p,0.001).

After controlling for age at diagnosis, sex, race, facility type, surgery status, adjunctive therapies, and insurance type, both the low-and middle-income brackets were associated with an independent increase in hazard (HR = 1.284 and 1.177 respectively; p,0.001). High income was associated with fewer comorbidities (72.2%) compared to low (65.9%) and middle-income (68.4%) patients (p,0.001). High-income patients were more likely to be treated at academic facilities (41.9%) compared to low (39.2%) or middle-income (35.4%) individuals (p,0.001), which have longer survivability (58.9 months vs. 47.8 months in non-academic facilities; p,0.001). Additionally, high income was also associated with increased rates of private insurance ownership (38.0%) while low-income individuals were more likely to have Medicaid (9.5%) or be uninsured (5.1%; p,0.001). No significant differences were found in tumor grade or differentiation, staging, metastasis, or surgical margins. Conclusions: This study indicates an association between high-income patients and increased survivability, while also observing an association with low-income and decreased survivability. Further research is required to assess specific environmental risk factors of adenomatous neoplasms and their relation to income level. Research Sponsor: None.

724 Poster Session

A novel classification of small bowel adenocarcinoma based on a hidden genome classifier: A multi-institutional study. First Author: Lauren E. Schleimer, Memorial Sloan Kettering Cancer Center, New York, NY Background: Small bowel adenocarcinoma (SBA) is a rare malignancy with poor prognosis. Data describing the clinical and pathologic characteristics of this disease are sparse, and few studies examine the genetic footprint of SBAs within the continuum of the gastrointestinal tract. Methods: All patients with small bowel adenocarcinoma for whom primary tumor tissue was available from 1993 to 2021 at six institutions were included. A hidden genome classifier (HGC) was developed based on genomic features from 286 gastroesophageal cancers (foregut) and 286 colorectal cancers (hindgut) using targeted tumor sequencing. The SBA samples were run through the HGC to obtain the predicted probability of either foregut or hindgut lineage. For patients submitted to curative intent resection, overall survival (OS) was calculated from 90 days post resection until date of last follow up. Cox regression was used to examine factors associated with OS and to construct the multivariable model. Results: Of a total of 243 patients with SBA, 60% were male. The most common anatomic locations were duodenum (53%), jejunum (28%), and ileum (12%). HGC prediction of foregut lineage was higher for duodenal (55%) and intestinal-type periampullary (64%) tumors, while prediction of hindgut lineage was higher for ileal (68%) and jejunal (54%) tumors. Patients were then divided into three HGC prediction groups based on the lowest-, highest-, and inter-quartile ranges: foregut (n=61

Gastrointestinal cancer trends in the Hispanic population: A SEER database population study (2000) (2001) (2002) (2003) (2004) (2005) (2006) (2007) (2008) (2009) (2010) (2011) (2012) (2013) (2014) (2015) (2016) (2017) (2018) (2019) . First Author: Sharon Hechter, Hackensack Meridian Ocean University Medical Center, Brick, NJ Background: Cancer continues to be the leading cause of death in the Hispanic population.

Gastrointestinal cancer surveillance data in Hispanic individuals has only recently become available in the last 3 decades. Differences in incidence rates among Hispanics and Non-Hispanic Whites (NHWs) need further elucidation. In this study, we analyzed trends in Hispanics and NHW populations across multiple gastrointestinal cancers. Methods: Gastrointestinal cancers (liver, colon and rectum, pancreas, esophagus, gallbladder, stomach, small intestine, anus, anal canal and anorectum) diagnosed between 2000-2019 were identified in the Surveillance, Epidemiology, and End Results Program (SEER) Database. We calculated incidence rates, confidence intervals and incidence rate ratios. Rates are per 100,000 and age adjusted to the 2000 US standard population. Rate ratios are the rounded rates in Hispanic individuals divided by the rounded rates in NHWs. Results: There was a higher incidence of liver, gallbladder, and stomach cancers among Hispanics when compared to NHWs between the years 2000-2019. Liver cancer incidence rate is (11.5 per 100,000) in Hispanics compared with (6.3 per 100, 000) in NHWs with an incidence rate ratio of 1.8. Gallbladder cancer incidence rate is (2.2 per 100,000) in Hispanics compared with (0.9 per 100,000) in NHWs with an incidence rate ratio of 2.4. Stomach cancer is (10.9 per 100,000) in Hispanics compared with (5.7 per 100,000) in NHWs with an incidence rate ratio of 1.9. The lowest incidence rate ratio was seen for anus, anal canal and anorectum cancers in Hispanics compared to NHWs. The incidence rate is (1.2 per 100,000) in Hispanics compared with (2.1 per 100,000) in NHWs with an incidence rate ratio of 0.6. Remaining cancers had incidence rate ratios less than 1.0 and were more likely to occur in NHWs. Conclusions: This study illustrates differing incidence rates of multiple gastrointestinal cancers among Hispanics compared to NHWs. Liver, gallbladder and stomach cancer incidence rates in Hispanics is double that of NHWs. Interestingly, the remaining gastrointestinal cancers had higher incidence rates among NHWs. Further research is warranted to understand the differences in cancer risk within the Hispanic population as well as healthcare access, language barriers and cultural differences that may play a role. Research Sponsor: None.

731 Poster Session

Patient-reported outcomes: The unmet needs of the gastrointestinal cancer community. First Author: Martha Raymond, GI Cancers Alliance, Dennisport, MA Background: According to the World Health Organization International Agency for Research on Cancer, gastrointestinal (GI) cancers account for 1 in 4 cancer cases and 1 in 3 cancer-related deaths worldwide. An estimated 4.8 million new cases of GI cancers and 3.4 million related deaths occur annually. Understanding the need for increased GI cancer awareness, patient education and support, the GI Cancers Alliance developed a series of engagement activities for the GI cancer community as a needs assessment to identify critical gaps in support services, fragmented education, and disease awareness. Methods: Our 12-month patient-reported outcomes (PRO) research included an online anonymous survey, individual and small group interviews, focus groups, advisory boards, and an interactive workshop at the 2023 American Society of Clinical Oncology annual meeting. 1,122 patients participated during this 12-month PRO research period. Participants reported being diagnosed with one of the following GI cancer primary tumor types: Anus (3%), Appendix (2%), Bile Duct (6%), Colon (19%), Esophagus (7%), Gallbladder (5%), Gastric (14%), GI NET / GI Carcinoid Tumor (3%), Liver (7%), Pancreas (6%), Small Intestine (4%), Rectum (23%), Unknown primary location (1%).

Results: Overarching areas of unmet need include: health disparities throughout the care continuum for underserved populations (21%); lack of adequate precision oncology patient education, including biomarker education and testing (19%); the rise of early-age onset (EAO) in GI cancers and the unique needs of the young adult (YA) population (18%); nutritional wellness education (17%); insufficient support for family caregivers and caregiver respite services (16%) scarcity of patient-centered care and adequate patient-clinician communication (11%). Conclusions: Our PRO research underscores the unmet needs and gaps in support services of the GI cancer community. Our global call to action includes partnering with our 100+ member organizations to amplify the patient voice and patient-lived experience, and crosscollaboration with our community of advocates, patients, caregivers, and clinicians.

Our shared call to action and continued collaboration provides a greater impact for our GI cancer community to help meet patient needs and eliminate critical gaps in services.

732 Poster Session

Patient-reported outcomes in patients with gastrointestinal cancer on oral chemotherapy. First Author: Kevin Juan Zhang, Beth Israel Deaconess Medical Center, Boston, MA Background: Over the last several years, patient reported outcomes (PROs) have been demonstrated to address patient symptoms, improve outcomes, and reduce health care utilization. We aim to provide an electronic PRO (ePRO) tool for gastrointestinal (GI) oncology patients with the goals of improving adherence, reducing toxicity, and enhancing patient access to the clinical team. Methods: Patients are provided an ePRO tool consisting of a cellphone app integrated into the electronic health record with questions on adherence and 10 questions on symptoms adapted from the NCI PRO-CTCAE for local use. Emails are sent to the clinical team for nonadherence, new or worsening symptoms, or patient requested callback. Outcomes including time to first symptom assessment, emergency department (ED) visit and/or hospitalization at 30 and 90 days from enrollment will be compared with historical controls. Other outcomes including adherence and patient-reported access to the clinic will be assessed.

Results: Six patients have been enrolled between May 1, 2023 and September 4, 2023.

Five patients were newly starting oral chemotherapy agents and one patient had already been on therapy. Types of cancers included colon cancers (2), rectal cancer (1), pancreatic cancer (1), GIST (1), and cholangiocarcinoma (1). Types of oral chemotherapy included capecitabine (4), olaparib (1), and imatinib (1). Five patients have submitted a total of ten responses. Of the five who completed the ePROs, patients responded a median of one time (range 1-5). Reported symptoms were fatigue (4), pain (2), nausea (1), diarrhea (1), other symptoms (2) and a request callback (1). Seven (70%) responses have prompted emails alerts for clinical symptoms and one (10%) for adherence concerns. All alerts were resolved; average time to alert response 1.6 calendar days (range 1-3). Among historical controls, time to first symptom assessment after a new oral chemotherapy prescription was seven days, 30-day rate for ED and/or hospitalizations was 12%, and 90-day rate of ED visits and/or hospitalizations was 28%. OTHER GI CANCER Visit meetings.asco.org and search by abstract for the full list of abstract authors and their disclosure information.

References

引用 / 出处

2024 ASCO GI 摘要集. 2024.