Domvanalimab and zimberelimab in advanced gastric, gastroesophageal junction or esophageal cancer: a phase 2 trial
Year: 2025
Type: article
Study design: Clinical Trial
Abstract: Dual inhibition of T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) and programmed cell death protein 1 (PD-1) may enhance antitumor immunity in advanced gastroesophageal cancers. Here we report the EDGE-Gastric study, an ongoing, multicenter, international, phase 2 study with three cohorts, one in the first-line setting (cohort A) and two in the second-line or greater setting (cohorts B and C). Cohort A comprises four arms: two nonrandomized (A1 and A2) and two randomized (A3 and A4). In arm A1, presented here, dual blockade of TIGIT and PD-1 with domvanalimab (Fc-silent anti-TIGIT) and zimberelimab (anti-PD-1) plus oxaliplatin, leucovorin, fluorouracil (FOLFOX) was evaluated in patients with previously untreated advanced HER2-negative gastric, gastroesophageal junction or esophageal adenocarcinoma. Among 41 treated patients, the confirmed objective response rate was 59% (90% confidence interval (CI) 44.5–71.6%), median progression-free survival was 12.9 months (90% CI 9.8–14.6 months) and median overall survival was 26.7 months (90% CI 18.4 months to not estimable (NE)). In patients with tumor area positivity ≥1% (PD-L1 positive) and tumor area positivity ≥5% (PD-L1 high), respectively, the objective response rate was 62% (90% CI 45.1–77.1%) and 69% (90% CI 45.2–86.8%), median progression-free survival was 13.2 months (90% CI 11.3–15.2 months) and 14.5 months (90% CI 11.3 months–NE), and median overall survival was 26.7 months (90% CI 19.5 months–NE) and not reached (90% CI 17.4 months–NE). Immune-related adverse events were reported in 27% of patients; the safety profile was consistent with that reported for anti-PD-1 plus platinum-based chemotherapy. Dual TIGIT and PD-1 blockade with domvanalimab and zimberelimab plus chemotherapy demonstrated encouraging efficacy, and the regimen is being evaluated in the phase 3 STAR-221 trial. ClinicalTrials.gov identifier: NCT05329766 . As presented at the ESMO Congress 2025: in this international, single-arm phase 2 trial, first-line treatment of patients with advanced gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma with domvanalimab (Fc-silent anti-TIGIT) and zimberelimab (anti-PD-1) plus FOLFOX (oxaliplatin, leucovorin and fluorouracil) led to encouraging objective response rates and survival outcomes, which will be validated in a phase 3 trial.
Source: Nature Medicine
Institutions: Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, Seoul National University, Seoul National University Hospital, Sarah Cannon, University of California, Los Angeles, Arcus Biosciences (United States), Gilead Sciences (United States), Yonsei University, Yonsei Cancer Hospital
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funders: U.S. Department of Defense, Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, GlaxoSmithKline, Gilead Sciences, Celgene, Array BioPharma, Handok, Merck KGaA, Taiho Pharmaceutical, Jazz Pharmaceuticals, Halozyme, Mersana Therapeutics, Cycle for Survival, BeiGene, Yuhan, Revolution Medicines, Silverback Therapeutics, MacroGenics, Castle Biosciences, Seagen, Eisai, Astellas Pharma, Servier, Ono Pharmaceutical, Ipsen, Plexxikon, Genentech, Merck Sharp and Dohme, National Cancer Institute, Daiichi Sankyo Europe
Award: Cancer Center Support Grant
OpenAlex ID: W4415310942