Perioperative tislelizumab plus chemotherapy for locally advanced gastric cancer: A randomized, prospective phase 2 trial.
Summary
This phase 2 study investigated the addition of tislelizumab to perioperative chemotherapy for patients with locally advanced gastric or gastroesophageal junction cancer. Patients were stratified by tumor-specific MHC class II (tsMHC-II) expression. The findings revealed that the combination immunotherapy significantly increased the major pathological response (mPR) rate in tsMHC-II-positive patients (61.8% vs. 26.5% with chemotherapy alone). No benefit was observed in the tsMHC-II-negative subgroup, indicating tsMHC-II as a promising predictive biomarker.
Analysis
This randomized, multicenter phase 2 trial (Mountain-02) provides Level II evidence for the efficacy of tislelizumab combined with perioperative chemotherapy in locally advanced gastric or gastroesophageal junction cancer patients, specifically those expressing tsMHC-II. The tsMHC-II biomarker emerges as a crucial predictive marker, as the significant benefit in major pathological response rate (61.8% vs 26.5%, p=0.003) was only observed in the tsMHC-II-positive subgroup. These findings warrant phase 3 trials to validate tsMHC-II as a patient selection biomarker. If confirmed, this could change clinical practice by enabling more precise patient selection for perioperative immunotherapy, with a potential clinical impact within 3-5 years.