Background
Randomised, prospective, biomarker-stratified, multicenter phase 2 trial (Mountain-02, NCT06374901), China; N=136. Operable cT3–4aN+M0 gastric/GEJ adenocarcinoma. Patients stratified by tumour-specific MHC class II (tsMHC-II) expression (standard IHC), then randomised 1:1. Tislelizumab = anti-PD-1.
Results
Interventions and follow up: Arm A: Perioperative tislelizumab + chemotherapy
Arm B: Perioperative chemotherapy alone
Primary endpoint: Major pathological response (mPR) rate in tsMHC-II-positive patients
mFollow up: NR in abstract
Results: mPR (tsMHC-II+): 61.8% vs 26.5%; P=.003 — primary endpoint met
mPR (tsMHC-II−): no significant benefit (NR)
Within combination arm (tsMHC-II+ vs −): mPR 61.8% vs 23.5% (P=.001); pCR 32.4% vs 5.9% (P=.006)
Arm B: Perioperative chemotherapy alone
Primary endpoint: Major pathological response (mPR) rate in tsMHC-II-positive patients
mFollow up: NR in abstract
Results: mPR (tsMHC-II+): 61.8% vs 26.5%; P=.003 — primary endpoint met
mPR (tsMHC-II−): no significant benefit (NR)
Within combination arm (tsMHC-II+ vs −): mPR 61.8% vs 23.5% (P=.001); pCR 32.4% vs 5.9% (P=.006)
Adverse events
Safety: NR in abstract
Conclusions
Adding perioperative tislelizumab to chemotherapy significantly improved mPR only in tsMHC-II-positive locally advanced gastric/GEJ cancer. tsMHC-II, assessable by routine IHC, emerges as a practical predictive biomarker for perioperative checkpoint blockade in gastric cancer.
Key Limitations
Phase 2, N=136; pathological surrogate endpoints (mPR/pCR) without EFS/OS data. Conducted exclusively in China (generalisability). Biomarker assay/cutoff requires prospective validation — a confirmatory tsMHC-II-selected randomised trial (NCT07068516) is ongoing.
Clinical Context
Perioperative immunotherapy in resectable gastric/GEJ cancer is advancing (MATTERHORN: durvalumab + FLOT, EFS benefit), but patient selection is unresolved — PD-L1 and MSI are imperfect predictors. tsMHC-II could refine selection for perioperative IO; not yet in guidelines; tislelizumab is not approved in this setting.