Current and Future Roles of Immunotherapy and Targeted Therapy in the Management of Advanced Gastroesophageal Cancers — Expert Second Option: Microlearning Activity 2

Faculty

TARGET AUDIENCE
This activity is intended for medical oncologists, hematology-oncology fellows and other healthcare providers involved in the treatment of gastroesophageal cancers.

LEARNING OBJECTIVES

• Describe published research data with immune checkpoint inhibitors alone or in combination with other systemic therapies in the management of metastatic gastric, gastroesophageal junction (GEJ) and esophageal cancers, and optimally integrate these strategies into current treatment algorithms.
• Assess available data with approved and investigational Claudin 18.2 (CLDN18.2) monoclonal antibody therapy-based combination approaches as first-line treatment for HER2-negative, CLDN18.2-positive gastric or GEJ cancer, and consider this information for current patient care.
• Review published and emerging research findings with novel HER2-targeted therapeutic approaches for HER2-positive gastroesophageal cancers, and assess their nonresearch role in patient care.
• Evaluate available treatment strategies for patients with gastric cancer and multiple biomarkers, such as HER2, PD-L1and CLDN18.2, and assess for optimal sequencing of available targeted therapies.
• Recall strategies commonly employed to mitigate and manage gastrointestinal side effects of CLDN18.2 monoclonal antibody-targeted therapy, and use this information to appropriately intervene when these side effects are suspected or diagnosed.

ACCREDITATION STATEMENT
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
Video Program: Research To Practice designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
Successful completion of these CME activities, which includes participation in the evaluation components and post-tests, enables the participant to earn up to 0.5 (video) Medical Knowledge MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for each activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

Please note, these programs have been specifically designed for the following ABIM specialty: medical oncology.

AMERICAN BOARD OF SURGERY (ABS) — CONTINOUS CERTIFICATION (CC)
Successful completion of these CME activities, which includes participation in the evaluation components and post-tests, enables the learner to earn credit toward the CME and Self-Assessment requirement(s) of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABS credit.

Please note, these programs have been specifically designed for the following ABS practice area: complex general surgical oncology.

PRIVACY POLICY
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HOW TO USE THIS CME ACTIVITY
To receive credit for an activity in this series, the participant should review the CME information, listen to or view the MP3s, complete the post-test with a score of 80% or better and fill out the evaluation. Program location URLs are noted below:

Video Program: ResearchToPractice.com/ASCOGI26/ImmunoTargetedGE/Micro/2/Video and evaluation ResearchToPractice.com/ASCOGI26/ImmunoTargetedGE/Micro/2/Video/CME.

CONTENT VALIDATION AND DISCLOSURES
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education and adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of an accredited continuing education activity, including faculty, planners, reviewers and others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant financial relationships have been mitigated prior to the commencement of these activities. In addition, all activity content is reviewed by RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.

FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

Jaffer A Ajani, MD
Professor of Medicine
Department of Gastrointestinal Medical Oncology
Division of Cancer Medicine
The University of Texas MD Anderson Cancer Center
Houston, Texas

Advisory Committees and Consulting Agreements: AstraZeneca Pharmaceuticals LP, BeOne, Bristol Myers Squibb, Daiichi Sankyo Inc, Gilead Sciences Inc, Henlius, Jazz Pharmaceuticals Inc, Merck, Taiho Oncology Inc, Zymeworks Inc; Contracted Research: AstraZeneca Pharmaceuticals LP, BeOne, Bristol Myers Squibb, Henlius, I-Mab Biopharma, Jazz Pharmaceuticals Inc, Merck, Servier Pharmaceuticals LLC.

Rutika Mehta, MD, MPH
Associate Professor, Division of Hematology/Oncology
Weill Cornell Medicine/NewYork-Presbyterian Hospital
New York, New York

Advisory Committees: Amgen Inc, Astellas, AstraZeneca Pharmaceuticals LP, BeOne, Bristol Myers Squibb, Daiichi Sankyo Inc, Eisai Inc, Gilead Sciences Inc, GSK, Jazz Pharmaceuticals Inc, Legend Biotech; Consulting Agreements: Jazz Pharmaceuticals Inc, Lilly, Replimune; Data and Safety Monitoring Boards/Committees: Arcus Biosciences, Gilead Sciences Inc; Nonrelevant Financial Relationships: Robert A Winn Career Development Award.

John Strickler, MD
Professor of Medicine
Associate Director, Clinical Research – GI
Co-Leader, Molecular Tumor Board
Duke University
Durham, North Carolina

Advisory Committees: AbbVie Inc, Alterome Therapeutics, Amgen Inc, Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, BeOne, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Cytovation ASA, Daiichi Sankyo Inc, Exelixis Inc, Full-Life Technologies, GE Healthcare, Genentech, a member of the Roche Group, GSK, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Jazz Pharmaceuticals Inc, Johnson & Johnson, Leap Therapeutics Inc, Lilly, Merck, Natera Inc, Pfizer Inc, Pheon Therapeutics, Quanta Therapeutics Inc, Regeneron Pharmaceuticals Inc, Revolution Medicines, Sanofi, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc, Tempus, Xilio Therapeutics; Contracted Research: AbbVie Inc, Alterome Therapeutics, Amgen Inc, Apollo Therapeutics, Astellas, Bayer HealthCare Pharmaceuticals, BeOne, Daiichi Sankyo Inc, Erasca, Genentech, a member of the Roche Group, GSK, Leap Therapeutics Inc, Lilly, Novartis, Pfizer Inc, Quanta Therapeutics Inc, Regeneron Pharmaceuticals Inc, Revolution Medicines; Data and Safety Monitoring Boards/Committees: AbbVie Inc, Johnson & Johnson; Stock OPTIONS — Private Companies: Triumvira Immunologics.

MODERATOR
Samuel J Klempner, MD
Program Director, Gastroesophageal Cancers
Tobins Family Endowed Chair in Esophagogastric Cancer
Massachusetts General Hospital
Associate Professor, Harvard Medical School
Boston, Massachusetts

Advisory Committees: Astellas, AstraZeneca Pharmaceuticals LP, BeOne, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Daiichi Sankyo Inc, Eisai Inc, Elevation Oncology, EsoBiotec, Gilead Sciences Inc, I-Mab Biopharma, Jazz Pharmaceuticals Inc, Merck, Mersana Therapeutics Inc, Natera Inc, Novartis, Signet Therapeutics, Taiho Oncology Inc; Consulting Agreements: Astellas; Contracted Research: Arcus Biosciences, AstraZeneca Pharmaceuticals LP, I-Mab Biopharma, Mersana Therapeutics Inc, Parabilis Medicines; Data and Safety Monitoring Boards/Committees: Sanofi; Stock OPTIONS — Private Companies: MBrace Therapeutics; Nonrelevant Financial Relationships: Debbie’s Dream Foundation, Degregorio Family Foundation, Gastric Cancer Foundation, National Cancer Institute/National Institutes of Health, NCCN (member of Gastric and Esophageal Guidelines Committees), Stand Up 2 Cancer/AACR, Torrey Coast Foundation.

EDITOR — Dr Love is president and CEO of Research To Practice. Research To Practice receives funds in the form of educational grants to develop CME activities from the following companies: Aadi Bioscience, AbbVie Inc, ADC Therapeutics, Agendia Inc, Alexion Pharmaceuticals, Amgen Inc, Array BioPharma Inc, a subsidiary of Pfizer Inc, Arvinas, Astellas, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, BeOne, Biotheranostics Inc, A Hologic Company, Black Diamond Therapeutics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Celcuity, Clovis Oncology, Coherus BioSciences, Corcept Therapeutics Inc, CTI BioPharma, a Sobi Company, Daiichi Sankyo Inc, Eisai Inc, Elevation Oncology Inc, Exact Sciences Corporation, Exelixis Inc, Genentech, a member of the Roche Group, Genmab US Inc, Geron Corporation, Gilead Sciences Inc, GSK, Helsinn Therapeutics (US) Inc, ImmunoGen Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Jazz Pharmaceuticals Inc, Johnson & Johnson, Karyopharm Therapeutics, Kite, A Gilead Company, Kura Oncology, Legend Biotech, Lilly, MEI Pharma Inc, Merck, Mersana Therapeutics Inc, Mirati Therapeutics Inc, Mural Oncology Inc, Natera Inc, Novartis, Novartis Pharmaceuticals Corporation on behalf of Advanced Accelerator Applications, Novocure Inc, Nuvalent, Nuvation Bio Inc, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, Puma Biotechnology Inc, Regeneron Pharmaceuticals Inc, Revolution Medicines Inc, Rigel Pharmaceuticals Inc, R-Pharm US, Sanofi, Seagen Inc, Servier Pharmaceuticals LLC, SpringWorks Therapeutics Inc, Stemline Therapeutics Inc, Sumitomo Pharma America, Summit Therapeutics, Syndax Pharmaceuticals, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc, TerSera Therapeutics LLC, and Tesaro, A GSK Company.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant financial relationships to disclose.

These educational activities contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

These activities are supported by educational grants from Astellas, BeOne, Gilead Sciences Inc, and Jazz Pharmaceuticals Inc.

Release date: April 2026
Expiration date: April 2027

After completing the post-test, learners may download and review the answers here in order to identify further areas of study.

Dr Ajani

Elimova E et al. Zanidatamab + chemotherapy (CT) ± tislelizumab for first-line (1L) HER2-positive (HER2+) locally advanced, unresectable, or metastatic gastroesophageal adenocarcinoma (mGEA): Primary analysis from HERIZON-GEA-01. Gastrointestinal Cancers Symposium 2026;Abstract LBA285.

Elimova E et al. Zanidatamab plus chemotherapy as first-line treatment for patients with HER2-positive advanced gastro-oesophageal adenocarcinoma: Primary results of a multicentre, single-arm, phase 2 study. Lancet Oncol 2025;26(7):847-59. Abstract

Meric-Bernstam F et al. Zanidatamab monotherapy or combined with chemotherapy in HER2-expressing gastroesophageal adenocarcinoma: A phase 1 trial. Nat Commun 2025;16(1):4293. Abstract

Shitara K et al. Trastuzumab deruxtecan or ramucirumab plus paclitaxel in gastric cancer. N Engl J Med 2025;393(4):336-48. Abstract

Dr Strickler

Ajani JA et al. Gastric cancer, version 2.2025, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2025;23(5):169-91. Abstract

Bray F et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024;74(3):229-63. Abstract

Kubota Y et al. Comprehensive clinical and molecular characterization of claudin 18.2 expression in advanced gastric or gastroesophageal junction cancer. ESMO Open 2023;8(1):100762. Abstract

Shah MA et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: The randomized, phase 3 GLOW trial. Nat Med 2023;29(8):2133-41. Abstract

Shitara K et al. Phase 2 ILUSTRO trial of 1L zolbetuximab plus mFOLFOX6 and nivolumab in patients with CLDN18.2+ locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. Gastrointestinal Cancers Symposium 2026;Abstract LBA284.

Shitara K et al. Zolbetuximab in gastric or gastroesophageal junction adenocarcinoma. N Engl J Med 2024;391(12):1159-62. Abstract

Shitara K et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): A multicentre, randomised, double-blind, phase 3 trial. Lancet 2023;401(10389):1655-68. Abstract

Dr Mehta

Janjigian YY et al. First-line nivolumab plus chemotherapy for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: 3-year follow-up of the phase III CheckMate 649 trial. J Clin Oncol 2024;42(17):2012-20. Abstract

Janjigian YY et al. Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: Interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. Lancet 2023;402(10418):2197-208. Abstract

Janjigian YY et al. Pembrolizumab plus trastuzumab and chemotherapy for HER2+ metastatic gastric or gastroesophageal junction (G/GEJ) cancer: Initial findings of the global phase 3 KEYNOTE-811 study. ASCO 2021;Abstract 4013.

Moehler MH et al. Rationale 305: Phase 3 study of tislelizumab plus chemotherapy vs placebo plus chemotherapy as first-line treatment (1L) of advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC). Gastrointestinal Cancers Symposium 2023;Abstract 286.

Qi C et al. Claudin18.2-specific CAR T cells (Satri-cel) versus treatment of physician’s choice (TPC) for previously treated advanced gastric or gastroesophageal junction cancer (G/GEJC): Primary results from a randomized, open-label, phase II trial (CT041-ST-01). ASCO 2025;Abstract 4003.

Qiu M et al. Tislelizumab (TIS) + chemotherapy (chemo) vs placebo (PBO) + chemo as first-line (1L) treatment in gastric/gastroesophageal junction adenocarcinoma (GC/GEJC) patients with/without peritoneal or liver metastases: A post hoc analysis of RATIONALE-305 study. Gastrointestinal Cancers Symposium 2025;Abstract 414.

Qiu MZ et al. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial. BMJ 2024;385:e078876. Abstract

Rha SY et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): A multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol 2023;24(11):1181-95. Abstract

Shah MA et al. Phase II study of telomelysin (OBP-301) in combination with pembrolizumab in gastroesophageal (GEA) adenocarcinoma. ASCO 2023;Abstract 4052.

Dr Klempner

Janjigian YY et al. CLARITY-Gastric 01: A randomized phase 3 study of AZD0901, a Claudin18.2 (CLDN18.2)-targeted antibody-drug conjugate, in second- or later-line (2L+) advanced gastric or gastroesophageal junction cancer (GC/GEJC). Gastrointestinal Cancers Symposium 2025;Abstract TPS507.

Janjigian YY et al. Domvanalimab and zimberelimab in advanced gastric, gastroesophageal junction or esophageal cancer: A phase 2 trial. Nat Med 2025;31(12):4274-80. Abstract

Liu JJ et al. Anti-claudin 18.2 (CLDN18.2) antibody-drug conjugate (ADC) IBI343 in patients (pts) with solid tumors and gastric/gastro-esophageal junction adenocarcinoma (G/GEJ AC): A phase I study. ESMO GI 2024;Abstract 396MO.

Rivera Herrero F et al. First-line rilvegostomig (rilve) + chemotherapy (CTx) in patients (pts) with HER2-negative (HER2–) locally advanced unresectable or metastatic gastric cancers: First report of GEMINI-Gastric sub study 2. ESMO 2024;Abstract 1422P.

Shitara K et al. Global prevalence of claudin 18 isoform 2 in tumors of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Gastric Cancer 2024;27(5):1058-68. Abstract

Xu R-H et al. CLDN18.2 targeted antibody-drug conjugate (ADC), SHR-A1904, in patients (pts) with gastric/gastroesophageal junction cancer (GC/GEJC): A phase I study. ESMO 2024; Abstract 609O.