Early Data Show Novel Immunotherapy Regimen May Improve Outcomes in Advanced Gastric Cancer

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Initial findings from the global phase II EDGE-Gastric trial indicate the potential for two novel immune checkpoint inhibitors to improve outcomes in advanced gastroesophageal adenocarcinoma. The findings were reported at the November 2023 ASCO Plenary Session by Yelena Y. Janjigian, MD, Chief of the Gastrointestinal Oncology Service at Memorial Sloan Kettering Cancer Center, New York.1

“The addition of domvanalimab and zimberelimab to FOLFOX shows encouraging objective response rates and 6-month progression-free survival in advanced gastroesophageal adenocarcinoma, irrespective of PD-L1 expression,” Dr. Janjigian said.

Yelena Y. Janjigian, MD

Yelena Y. Janjigian, MD

The EDGE-Gastric trial is a multiarm study exploring the addition of two investigational therapies—domvanalimab, a monoclonal antibody targeting anti–T-cell immunoglobulin and ITM domain (TIGIT), and zimberelimab, an inhibitor of PD-1—to FOLFOX (fluorouracil, leucovorin, oxaliplatin) as first-line treatment. It is evaluating three cohorts based on previous treatment and line of therapy. Dr. Janjigian reported the first efficacy and safety results of Arm A1.

As Dr. Janjigian explained, a PD-1 inhibitor combined with front-line chemotherapy is currently the standard of care in metastatic gastroesophageal cancer, but patients typically develop resistance to this regimen. The study is evaluating the potential benefit of inhibiting TIGIT, an immune receptor on some T cells and natural killer cells. “Dual anti–PD-1 and anti-TIGIT increases tumor antigen–specific CD8-positive T-cell expansion, with potent preclinical antitumor activity,” she said.

About EDGE-Gastric

The study enrolled 120 patients with previously untreated locally advanced unresectable or metastatic gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma. In the Arm A1 cohort, 41 patients received first-line therapy with domvanalimab, zimberelimab, and FOLFOX for a median of 33 weeks. The primary endpoints are investigator-assessed objective response rate and safety.

In the Arm A1 cohort, 63% of patients had stomach cancer, 32% had liver metastases, 59% had a PD-L1 tumor area positivity score < 5%, and 59% had microsatellite-stable tumors (2% were known to be microsatellite instability–high).


  • The global phase II EDGE-Gastric trial is evaluating two novel immune checkpoint inhibitors—domvanalimab and zimberelimab—plus chemotherapy in advanced gastric cancer, gastroesophageal cancer, and esophageal adenocarcinoma.
  • The overall response rate was 59%, rising to 80% in patients with PD-L1–positive tumors.
  • Investigators are assessing this regimen in the hope that it will improve upon the benefit already established for PD-1 inhibitors in this malignancy.

The intent-to-treat assessment confirmed an objective response rate of 59% for all patients on the study; the median progression-free survival was not reached, and the progression-free survival rate was 77% at 6 months. In patients with high PD-L1 expression (≥ 5%), the response rate was 80% (with one complete response), median progression-free survival was not reached, and 93% were progression-free at 6 months, Dr. Janjigian reported.

“There are some partial responses that are still ongoing and need to be confirmed,” she commented. “Most of the patients derived benefit and had disease control from this regimen of domvanalimab and zimberelimab plus FOLFOX, irrespective of PD-L1 status…. Most of the patients are still on treatment, so these data are yet to be mature.”

Serious treatment-related side effects occurred in 24% of patients, with 5% considered to be drug-related and mostly attributed to chemotherapy. Grade ≥ 3 treatment-related adverse events related to any study drug were reported in 56% of patients, with 49% discontinuing a study drug as a result. Immune-mediated adverse events were uncommon and generally thought to be mild. “The incidence of adverse events was similar to prior experience with anti–PD-1 plus FOLFOX, and there were no new safety concerns identified,” she said.

Dr. Janjigian noted these results led to the phase III STAR-221 trial ( identifier NCT05568095). This trial, which is currently recruiting patients across five continents, is comparing domvanalimab and zimberelimab plus chemotherapy against nivolumab plus chemotherapy as a first-line treatment in locally advanced unresectable or metastatic gastric, gastroesophageal junction, and esophageal adenocarcinoma, irrespective of PD-L1 status. 

DISCLOSURE: Dr. Janjigian has received fees for consulting and travel from AmerisourceBergen, Arcus Biosciences, AstraZeneca, Basilea Pharmaceutica, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Geneos Therapeutics, GlaxoSmithKline, Imedex, Imugene, Lynx Health, Merck, Merck Serono, Michael J. Hennessy Associates, Paradigm Medical Communications, PeerView Institute, Pfizer, RGENIX, Seagen, Silverback Therapeutics, and Zymeworks and has stock options with RGENIX.


1. Janjigian Y, Oh DY, Pelster M, et al: EDGE-Gastric Arm A1. ASCO Plenary Series: November 2023 Session. Abstract 433248. Presented November 7, 2023.


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