Preoperative PD-1 inhibitor (tislelizumab) plus SOX for locally advanced gastric or gastro-oesophageal junction cancer: Results from a single-arm, phase II trial.

e16140 Background: Although perioperative chemotherapy is the standard treatment regimen for locally advanced gastric cancer, the pathological complete response (pCR) rate and disease-free survival (DFS) are limited. Immunotherapy combined chemotherapy has been investigated to improve survival in advanced gastric cancer. However, the efficacy of immunotherapy in the perioperative therapy has not yet been validated. We conducted a single-arm, phase II trial to evaluate the efficacy and safety of immunotherapy combined with chemotherapy in locally advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. Methods: Patients with resectable gastric or GEJ cancer clinically staged as cT3N+M0 or cT4NanyM0 received three or four preoperative 3-week cycles of SOX plus PD-1 antibody tislelizumab, followed by D2 gastrectomy within 2-4 weeks. The primary endpoint was major pathological response (MPR) rate. The secondary endpoints were pCR rate, objective response rate, DFS, overall survival and safety. Results: Study accrual completed at Oct. 2024, 31 patients with a median age of 67 years (range: 33-77) were enrolled. 77.4% were male, 96.8% had lymph node metastasis and 77.4% had T4 stage. Four patients were undergoing preoperative treatment and were therefore excluded from the efficacy and safety analysis set. 66.7% (18/27) patients completed three to four cycles of preoperative tislelizumab and SOX. R0 resection rate was 96.3% (26/27). The MPR rate was 37.0% (10/27) and the pCR rate was 18.5% (5/27). Tislelizumab combined SOX exhibited significant response of MPR in patients with diffuse classification than patients with intestinal and mixed (62.5% vs 18.75%, p = 0.04). High MPR rates were also observed in patients with combined positive score (CPS) ≥ 5 of programmed cell death ligand-1 (PD-L1) expression and signet ring cell composition (50%, 50%, respectively).The surgical morbidity was 3.7% (1/27), and no 30-day mortality was observed. Treatment-related grade 3-4 adverse events was 3.7% (1/27). Conclusions: Preoperative PD-1 antibody tislelizumab plus chemotherapy demonstrated a significantly improved pathological regression in patients with locally advanced resectable G/GEJ adenocarcinoma, especially in those with diffuse G/GEJ. And the safety of this therapy is controllable, which might be a promising option for patients with locally advanced resectable G/GEJ adenocarcinoma.