A phase II study of Zimberelimab anti PD1 immunOtherapy +/- Domvanalimab anti-TIGIT therapy in resectable mismatch repair deficient gastric/gastro-oesophageal junctional AdenoCarinoma (ZODIAC)

A clinical trial is testing whether adding a second immunotherapy drug to a standard checkpoint inhibitor can shrink stomach cancers before surgery and keep them from returning. This matters because mismatch repair deficient gastric cancers are particularly sensitive to immunotherapy, but many patients still relapse after surgery. The current standard of care—chemotherapy plus surgery—does not work well for this specific tumour type. The trial compares the PD-1 inhibitor zimberelimab alone against the same drug combined with domvanalimab, which blocks a different immune checkpoint called TIGIT. The idea is that blocking two checkpoints simultaneously might unleash a stronger and more durable immune attack on the tumour. If the combination proves more effective, it could change how these patients are treated before and after surgery. Instead of relying on chemotherapy, which has significant side effects, surgeons might offer a targeted immunotherapy regimen that spares healthy tissue while eliminating cancer cells. This would directly improve outcomes for a group of patients who currently have limited options. The trial is a proof-of-concept study, meaning it will determine whether a larger phase III trial is warranted.