4083 Background: The combination of PD-1 antibody and chemotherapy was shown to be effective in advanced gastric cancer, but has not yet been comprehensively investigated in locally advanced patients, especially in the context of adenocarcinoma of gastro-oesophageal junction (GEJ). In this study, we conducted a prospective, nonrandomized, open-label phase II trial to evaluate the effectiveness of adding PD-1 antibody to perioperative chemotherapy in patients with locally advanced resectable GEJ cancer. Methods: In this nonrandomized, open-label, phase II study, patients with resectable GEJ adenocarcinoma clinically staged as cT3-4aNanyM0 or cT1-2N+M0 were allocated three preoperative and five postoperative 3-week cycles of PD-1 antibody tislelizumab plus SOX (S-1 and oxaliplatin) regimen. The primary endpoint was major pathological response (MPR) rate. The secondary endpoints were pathological complete response (pCR), pathological complete /moderate regression rate (TRG 0/1), R0 resection rate, recurrence-free survival, event-free survival, overall survival, treatment safety and quality of life. The trial is registered at Chinese Clinical Trial Registry, identifier: ChiCTR2200058732. Results: Between Oct 2022 and June 2023, 32 patients were enrolled and assessed using intention-to-treat analysis. The median age was 60 years (range: 28-74 years), and 53.1% (17/32) patients were Siewert III type. All patients received at least one cycle of assigned preoperative treatment, and 96.9% (31/32) patients completed three cycles of assigned preoperative tislelizumab and SOX. R0 resection rate was 96.9% (31/32). The MPR rate was 37.5% (12/32, 95% CI: 21.1%-56.3%) and the pCR rate was 28.1% (9/32, 95% CI: 13.7%-46.7%). The surgical morbidity was 12.5% (4/32), and no 30-day mortality was observed. In the preoperative and postoperative treatment period, treatment-related grade 3-4 adverse events was 9.4% (3/32). At the date of 6th Feb 2024, three (9.4%) patients occurred recurrence. Conclusions: This is the first prospective study that focus on the perioperative immunotherapy in patients with resectable GEJ adenocarcinoma. Perioperative PD-1 antibody tislelizumab plus chemotherapy demonstrated a significantly improved pathological regression and might be a promising option for patients with locally advanced resectable GEJ adenocarcinoma. Clinical trial information: ChiCTR2200058732.