GEMINI-Perioperative (PeriOp) Gastric: A phase 2 study of novel agent-based combinations as PeriOp therapy for previously untreated, locally advanced resectable gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma.

Abstract

TPS469 Background: The standard-of-care treatment for resectable gastric cancer with a high risk of relapse is PeriOp FLOT (5-fluorouracil [5-FU] + leucovorin [isovorin in Japan] + oxaliplatin + docetaxel) and radical surgery. In the MATTERHORN trial, durvalumab + FLOT improved event-free survival versus FLOT alone, establishing a role for immunotherapy + chemotherapy in this setting (Janjigian YY, et al. N Engl J Med 2025;393:217–30). Methods: GEMINI-PeriOp Gastric (NCT07069712) is an ongoing, open-label, phase 2 platform study of innovative treatment combinations given as neoadjuvant and adjuvant therapy for resectable gastric cancers. Eligible patients are aged ≥18 years with previously untreated, locally advanced resectable gastric, GEJ, or esophageal adenocarcinoma, an Eastern Cooperative Oncology Group performance status of 0/1, and CLDN18.2, HER2, and PD-L1 status confirmed by immunohistochemistry. The study currently comprises three substudies assessing combinations containing rilvegostomig (an anti-PD-1/TIGIT bispecific antibody) in ~100 patients overall. In substudy 1, CLDN18.2-positive/HER2-negative patients will receive intravenous (IV) sonesitatug vedotin (AZD0901, a CLDN18.2-targeted antibody-drug conjugate) + IV rilvegostomig + 5-FU or capecitabine; in substudy 2, HER2-positive patients will receive IV trastuzumab deruxtecan + IV rilvegostomig + 5-FU or capecitabine; in substudy 3, patients will receive IV rilvegostomig + FLOT. Optional rilvegostomig monotherapy may be given after completing adjuvant combination therapy in all three substudies. The primary objectives are the safety and tolerability of PeriOp therapy and the pathological complete response rate. Secondary objectives include the feasibility of surgery, complete resection rate, tumor downstaging, objective response rate, event-free, disease-free, and overall survival, and the pharmacokinetics and immunogenicity of the investigational products. Enrollment began in July 2025. Clinical trial information: NCT07069712 .