ASCO 2026, taking place May 29–June 2 at McCormick Place in Chicago, Illinois, with online access, is expected to deliver practice-relevant updates across a broad range of malignancies. The program will feature biomarker-defined treatment strategies, novel antibody and antibody-drug conjugate platforms, dual immune checkpoint blockade approaches, perioperative optimization, switch maintenance strategies, and long-term follow-up analyses across multiple disease settings.
This article highlights top phase 3 trials and additional studies in gastroesophageal cancers — including gastric, gastroesophageal junction (GEJ), and esophageal adenocarcinoma — scheduled for presentation at ASCO 2026, with potential to inform clinical practice and contribute to the evolution of future standards of care.
HERIZON-GEA-01: Zanidatamab + Chemotherapy ± Tislelizumab for 1L HER2-Positive Locally Advanced or Metastatic Gastroesophageal Adenocarcinoma
Abstract: 4010
Presenter: Sun Young Rha (Seoul, South Korea)
Trial Type: Phase III, Randomized
Session: Rapid Oral Abstract Session
HERIZON-GEA-01 is a global, randomized phase III trial evaluating zanidatamab plus chemotherapy, with or without tislelizumab, versus trastuzumab plus chemotherapy as first-line treatment for HER2-positive locally advanced unresectable or metastatic gastroesophageal adenocarcinoma. Zanidatamab is a bispecific, biparatopic anti-HER2 antibody designed to enhance HER2 clustering and immune engagement, while tislelizumab is an anti-PD-1 monoclonal antibody engineered to minimize Fcγ receptor binding on macrophages.
This analysis focuses on outcomes by PD-L1 expression status, examining whether the benefit of zanidatamab-based regimens, with or without the addition of tislelizumab, is modulated by baseline PD-L1 levels. The subgroup evaluation is particularly relevant given the established role of PD-L1 as a predictive biomarker for immune checkpoint inhibitor efficacy in HER2-positive gastroesophageal adenocarcinoma.
This presentation addresses whether PD-L1 status should guide selection of the optimal first-line HER2-targeted backbone in advanced disease.
Read about HERIZON-GEA-01 from ASCO GI 2026 on OncoDaily.
Disitamab Vedotin Plus Trastuzumab and Tislelizumab Versus CAPOX Chemotherapy Plus Trastuzumab ± Pembrolizumab as First-Line Treatment for HER2-High Advanced Gastric/Gastroesophageal Junction Adenocarcinoma
Abstract: TPS4245
Presenter: Zhi Peng (Beijing, China)
Trial Type: Phase III, Randomized (Trial in Progress)
Session:Poster Session
This randomized phase III trial evaluates disitamab vedotin, a HER2-directed antibody-drug conjugate, in combination with trastuzumab and tislelizumab, versus standard CAPOX chemotherapy plus trastuzumab with or without pembrolizumab, as first-line treatment for patients with HER2-high advanced gastric or gastroesophageal junction adenocarcinoma. Disitamab vedotin consists of a HER2-targeting monoclonal antibody conjugated to the microtubule inhibitor monomethyl auristatin E, designed to deliver cytotoxic payload selectively to HER2-expressing tumor cells.
The study is designed to assess whether a chemotherapy-free regimen combining HER2-directed antibody-drug conjugate, HER2 antibody, and PD-1 blockade can improve outcomes over current standards built on chemotherapy and HER2-targeted therapy. Endpoints include progression-free survival, overall survival, objective response rate, duration of response, and safety.
This trial-in-progress presentation addresses whether disitamab vedotin–based combinations can redefine the first-line treatment paradigm for HER2-high advanced gastric and gastroesophageal junction adenocarcinoma by moving beyond chemotherapy backbones.
CheckMate-649: Heterogeneity in Biomarkers for Advanced Gastric Cancer, Gastroesophageal Junction Cancer, and Esophageal Adenocarcinoma Across Regions
Abstract: 4056
Presenter: Lin Shen (Beijing, China)
Trial Type: Exploratory Analysis (Phase III trial dataset)
Session:Poster Session
CheckMate-649 is a global, randomized phase III trial that established nivolumab plus chemotherapy as a first-line standard of care for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma. This analysis examines regional heterogeneity in key biomarkers across the trial population, including PD-L1 combined positive score, microsatellite instability status, HER2 expression, and other molecular and clinicopathologic characteristics.
The evaluation explores how biomarker distribution varies across geographic regions and whether such differences may influence treatment response, prognosis, and the generalizability of trial outcomes to distinct patient populations.
This presentation addresses the role of regional biomarker heterogeneity in interpreting global trial data and informing biomarker-guided treatment strategies in advanced gastroesophageal adenocarcinoma.
Read about CheckMate-649 on OncoDaily.
ATTRACTION-6: Nivolumab plus Ipilimumab plus Chemotherapy as 1L Treatment for HER2-Negative Unresectable Advanced or Recurrent GC/GEJ
Abstract: 4006
Presenter: Do-Youn Oh (Seoul, South Korea)
Trial Type: Phase III, Randomized
Session: Oral Abstract Session
ATTRACTION-6 is a randomized phase III trial evaluating the addition of dual immune checkpoint blockade with nivolumab plus ipilimumab to chemotherapy as first-line treatment for patients with HER2-negative unresectable advanced or recurrent gastric and gastroesophageal junction cancer. The study builds on the established role of nivolumab plus chemotherapy in this setting and explores whether combined PD-1 and CTLA-4 inhibition can further improve outcomes.
Endpoints include overall survival and progression-free survival, with additional assessments of objective response rate, duration of response, safety, and outcomes across PD-L1–defined subgroups.
This presentation addresses whether intensifying the immunotherapy backbone with dual checkpoint blockade provides incremental benefit over current first-line standards in HER2-negative advanced gastric and gastroesophageal junction cancer.
MATTERHORN: A Randomized Phase 3 Study of Durvalumab Plus FLOT Chemotherapy in Resectable Gastric/Gastroesophageal Junction Cancer
Abstract: 4070
Presenter: Zev A. Wainberg (Los Angeles, United States)
Trial Type: Phase III, Randomized
Session:Poster Session
MATTERHORN is a global, randomized, double-blind phase III trial evaluating perioperative durvalumab in combination with 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy, followed by adjuvant durvalumab, versus FLOT alone in patients with resectable gastric or gastroesophageal junction cancer. The study is designed to assess whether the addition of PD-L1 blockade to standard perioperative chemotherapy improves long-term outcomes in the curative-intent setting.
This analysis focuses on the efficacy contribution of durvalumab and characterizes safety across distinct treatment periods, including neoadjuvant, perioperative, and adjuvant phases. Endpoints include event-free survival, pathological complete response, and period-specific treatment-emergent adverse events, dose modifications, and discontinuation rates.
On March 16, 2026, the European Commission had approved durvalumab (Imfinzi) plus perioperative FLOT chemotherapy for adult patients with resectable early-stage and locally advanced (Stages II, III, IVA) gastric and gastroesophageal junction cancers.
You can read about EC approval on OncoDaily.
KEYNOTE-811: 6-Year Median Follow-Up of Pembrolizumab Plus Trastuzumab and Chemotherapy for Previously Untreated Advanced HER2-Positive GC/GEJ
Abstract: 4040
Presenter: Akihito Kawazoe (Kashiwa, Japan)
Trial Type: Phase III, Randomized, Double-Blind
Session: Poster Session
KEYNOTE-811 is a global, randomized, double-blind phase III trial evaluating pembrolizumab in combination with trastuzumab and chemotherapy versus placebo plus trastuzumab and chemotherapy as first-line treatment for patients with previously untreated advanced HER2-positive gastric or gastroesophageal junction adenocarcinoma. The study established the role of adding PD-1 blockade to HER2-directed therapy and chemotherapy in this biomarker-defined population.
This analysis reports outcomes at a 6-year median follow-up, providing long-term data on overall survival, progression-free survival, duration of response, and safety, with particular attention to outcomes in PD-L1–defined subgroups.
The presentation addresses the durability of benefit with pembrolizumab plus trastuzumab and chemotherapy and further informs its role as a first-line standard in advanced HER2-positive gastroesophageal adenocarcinoma.
KEYNOTE-585: Neoadjuvant and Adjuvant Pembrolizumab Plus Chemotherapy for Locally Advanced GC/GEJ
Abstract: 4074
Presenter: Sun Young Rha (Seoul, South Korea)
Trial Type: Phase III, Randomized, Double-Blind
Session: Poster Session
KEYNOTE-585 is a global, randomized, double-blind phase III trial evaluating perioperative pembrolizumab in combination with chemotherapy versus placebo plus chemotherapy in patients with locally advanced resectable gastric or gastroesophageal junction adenocarcinoma. The study was designed to assess whether the addition of PD-1 blockade to standard neoadjuvant and adjuvant chemotherapy improves long-term outcomes in the curative-intent setting.
This analysis focuses on the microsatellite instability-high (MSI-H) subgroup, a biomarker-defined population known to derive enhanced benefit from immune checkpoint inhibition. Endpoints include event-free survival, overall survival, pathological complete response, and safety within this subset.
The presentation addresses whether MSI-H status identifies patients most likely to benefit from perioperative pembrolizumab plus chemotherapy, helping to refine biomarker-guided treatment strategies in locally advanced gastroesophageal adenocarcinoma.
Read more about KEYNOTE-585 on OncoDaily.
RATIONALE-305: Quality-Adjusted Survival Comparison for Tislelizumab Plus Chemotherapy Versus Placebo Plus Chemotherapy as First-Line Treatment in Gastric/Gastroesophageal Junction Adenocarcinoma Patients with Peritoneal Metastasis — Long-Term Follow-Up
Abstract: 4034
Presenter: Rutika Mehta (New York, United States)
Trial Type: Phase III, Randomized, Double-Blind (Subgroup Analysis)
Session: Poster Session
RATIONALE-305 is a global, randomized, double-blind phase III trial evaluating tislelizumab, an anti-PD-1 monoclonal antibody, in combination with chemotherapy versus placebo plus chemotherapy as first-line treatment for patients with HER2-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.
This analysis focuses on the subgroup of patients with peritoneal metastasis, a population known to experience particularly poor prognosis and symptom burden. Using a quality-adjusted survival framework, the evaluation integrates long-term follow-up data on overall survival with health-related quality of life measures to quantify the balance between treatment benefit and toxicity over time.
The presentation addresses whether tislelizumab plus chemotherapy offers meaningful quality-adjusted survival gains in patients with peritoneal metastasis, helping to inform first-line treatment decisions in this high-risk subgroup of advanced gastroesophageal adenocarcinoma.
You can read about RATIONALE-305 results at ASCO GI 2026 on OncoDaily.
DESTINY-Gastric 04: A Randomized Phase 3 Study of Trastuzumab Deruxtecan vs Ramucirumab Plus Paclitaxel in Patients with HER2-Positive Unresectable/Metastatic GC/GEJ Adenocarcinoma
Abstract: 4111
Presenter: Kohei Shitara (Kashiwa, Japan)
Trial Type: Phase III, Randomized
Session: Poster Session
DESTINY-Gastric04 is a global, randomized phase III trial evaluating trastuzumab deruxtecan (T-DXd), a HER2-directed antibody-drug conjugate, versus ramucirumab plus paclitaxel in patients with HER2-positive unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma who progressed on or after a prior trastuzumab-based regimen.
This analysis reports additional health-related quality of life (HRQoL) outcomes using validated patient-reported instruments, including assessments of global health status, functional domains, and disease-specific symptoms. Endpoints include time to deterioration and change from baseline across key HRQoL scales.
The presentation addresses whether T-DXd preserves or improves quality of life relative to ramucirumab plus paclitaxel, complementing prior efficacy and safety data and informing its role in the second-line treatment of HER2-positive advanced gastroesophageal adenocarcinoma.
ARMANI: Impact of Molecular Profile on Switch Maintenance to Paclitaxel Plus Ramucirumab Versus Continuation of First-Line Fluoropyrimidine and Oxaliplatin Chemotherapy in Patients with Advanced HER2-Negative GC/GEJ Cancer
Abstract: 4060
Presenter: Paolo Manca (Milan, Italy)
Trial Type: Phase III, Randomized (Exploratory Endpoint)
Session: Poster Session
ARMANI is a randomized phase III trial evaluating switch maintenance therapy with paclitaxel plus ramucirumab versus continuation of first-line fluoropyrimidine and oxaliplatin chemotherapy in patients with advanced HER2-negative gastric or gastroesophageal junction cancer who achieved disease control after induction chemotherapy. The study was designed to assess whether an early switch to a non–cross-resistant regimen can improve outcomes over continued standard chemotherapy.
This exploratory analysis investigates the impact of baseline molecular profile on the efficacy of switch maintenance, examining key biomarkers and genomic alterations relevant to HER2-negative gastroesophageal adenocarcinoma. Endpoints include progression-free survival and overall survival across molecularly defined subgroups.
The presentation addresses whether molecular characterization can identify patients who derive the greatest benefit from switch maintenance with paclitaxel plus ramucirumab, supporting biomarker-guided treatment sequencing in advanced HER2-negative gastric and gastroesophageal junction cancer.
Find more information on official ASCO website.