This is a Phase Ⅲ, randomized, open-label, Sponsor-blinded, 3-arm, global, multicenter study assessing the efficacy and safety of rilvegostomig in combination with fluoropyrimidine and T-DXd (Arm A) compared to trastuzumab, chemotherapy, and pembrolizumab (Arm B) in HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma participants whose tumors express PD L1 CPS ≥ 1. Rilvegostomig in combination with trastuzumab and chemotherapy will be evaluated in a separate arm (Arm C) to assess the contribution of each component in the experimental arm.
HER2 positive for gastric cancer on a tumor biopsy.
PD-L1 combined positive score (CPS) ≥ 1.
Provision of tumor tissue sample from recent biopsy adequate for HER2 and PD-L1 testing.
Previously untreated, unresectable, locally advanced or metastatic gastric or GEJ adenocarcinoma.
Lack of physiological integrity of the upper gastrointestinal tract.
Known dihydropyrimidine dehydrogenase enzyme deficiency.
Contraindication to pembrolizumab or trastuzumab, contraindications to fluoropyrimidine (5-FU and capecitabine) or platinum (cisplatin and oxaliplatin) treatment as per local label.
History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study intervention and of low potential risk for recurrence.