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.
Parallel
Rilvegostomig
DrugQ3W, intravenous infusion
Trastuzumab deruxtecan
DrugQ3W, intravenous infusion
Trastuzumab
DrugQ3W, intravenous infusion
Pembrolizumab
DrugQ3W, intravenous infusion
5-fluorouracil
DrugQ3W, intravenous infusion
Capecitabine
DrugBID, oral administration
Cisplatin
DrugQ3W, intravenous infusion
Oxaliplatin
DrugQ3W, intravenous infusion
Progression free survival (PFS)
PFS is defined as time from randomization until progression per RECIST v1.1, or death due to any cause.
Overall Survival (OS)
OS is defined as time from randomization until the date of death due to any cause.
Objective Response Rate (ORR)
ORR according to RECIST v1.1. ORR is defined as the proportion of participants who have a complete response (CR) or partial response (PR).
Duration of Response (DoR)
DoR according to RECIST v1.1. DoR will be defined as the time from the date of first documented response until date of documented progression per RECIST v1.1 or death due to any cause.
Proportion of all randomized participants alive and progression-free at 6 months (PFS6)
Proportion of all randomized participants alive and progression-free at 6 months calculated for progression.
Proportion of all randomized participants alive and progression-free at 12 months (PFS12)
Proportion of all randomized participants alive and progression-free at 12 months calculated for progression.
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