Background/Objectives: Immunotherapy (IO) has demonstrated survival benefits in metastatic gastroesophageal cancers, and current data supports perioperative IO in localized adenocarcinomas. Radiation may further enhance IO response through immunologic priming. This study evaluates the feasibility, safety, and preliminary efficacy of incorporating IO into a chemoradiation-based perioperative strategy for resectable gastric and gastroesophageal junction (GEJ) adenocarcinoma. Methods: This single-arm, phase I/II study enrolled adults with untreated, locally advanced, resectable gastric or GEJ adenocarcinoma between February 2019 and June 2023. The treatment protocol consisted of induction chemotherapy (oxaliplatin + 5-fluorouracil), induction IO (nivolumab + ipilimumab), concurrent immune-chemoradiation (nivolumab, 5-fluorouracil, and 45 Gy IMRT/VMAT), surgical resection, and adjuvant nivolumab for residual disease. Primary endpoints were safety and feasibility; secondary endpoints included the pathologic complete response (pCR), R0 resection rate, disease-free survival (DFS), overall survival (OS), and biomarker analysis. Results: In total, 30 patients were enrolled, and 23 underwent resection. Grade 4 treatment-related toxicities occurred in three patients (10%), including acute kidney injury, myocarditis/myositis/myasthenia gravis overlap syndrome, and neutropenia. Among surgical patients, the pCR rate was 39.1% (95% CI: 19.7–61.5%), and the intention-to-treat pCR rate was 30% (95% CI: 14.7–49.4%). R0 resection was achieved in 87% of cases. Median DFS among resected patients was 40.2 months (95% CI: 21.6–NE). Median OS was 43.7 months (95% CI: 30.7–NE), with 2-, 3-, and 5-year OS rates of 73.3%, 57.5%, and 47.9%, respectively. Conclusions: This multimodality approach incorporating IO with chemotherapy and chemoradiation demonstrated a manageable safety profile and an encouraging pCR rate, supporting further evaluation.
Murphy et al. (2026) studied this question.