Perioperative PD-1 antibody toripalimab combined with chemotherapy versus chemotherapy alone in locally advanced gastric or gastroesophageal junction cancer: 3-year follow-up of the prospective, randomized, phase 2 NEOSUMMIT-01 trial.

282 Background: The NEOSUMMIT-01 trial evaluated the efficacy of adding the PD-1 antibody toripalimab to perioperative chemotherapy in patients with locally advanced, resectable gastric or gastroesophageal junction (GEJ) cancer. Previously, we reported significant improvements in pathological complete or moderate regression (TRG 0/1) rate (44.4% vs 20.4%, P =0.009) and pathological complete response (pCR) rate (22.2% vs 7.4%, P =0.030) with the addition of toripalimab (2023 ASCO Abstract 4001; Nature Medicine 2024). Here, we present the 3-year survival outcomes after extended follow-up. Methods: In this open-label, randomized, phase 2 trial, patients with resectable gastric or GEJ cancer (clinical stage cT3–4a N+ M0) were randomized (1:1) to receive either three preoperative and five postoperative cycles of SOX/XELOX chemotherapy (chemotherapy group), or the same chemotherapy combined with toripalimab, followed by toripalimab monotherapy for 6 months (toripalimab plus chemotherapy group). The primary endpoint was pathological complete or moderate regression rate (TRG 0/1). Secondary endpoints included pathological complete response (pCR), R0 resection rate, objective response rate, disease control rate, event-free survival (EFS), overall survival (OS), and treatment safety. This analysis focuses on 3-year EFS and OS, assessed in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT04250948). Results: Between October 12, 2019, and June 27, 2022, 108 patients were enrolled (toripalimab plus chemotherapy, n = 54; chemotherapy alone, n = 54) and included in the intention-to-treat analysis. As of the clinical cutoff date (August 29, 2025), the median follow-up was 43.2 months (IQR 36.6–53.7). The 3-year EFS was 74.7% (95% CI: 63.6–87.7%) in the toripalimab plus chemotherapy group and 56.2% (95% CI: 43.3–73.0%) in the chemotherapy group, with a hazard ratio (HR) of 0.52 (95% CI: 0.27–1.00; P = 0.047). The 3-year OS was 81.3% (95% CI: 71.4–92.4%) versus 72.2% (95% CI: 61.2–85.2%), respectively, with an HR of 0.45 (95% CI: 0.21–0.95; P = 0.031). Conclusions: Perioperative toripalimab combined with chemotherapy demonstrated significantly improved 3-year EFS and OS compared to chemotherapy alone, suggesting it as a promising treatment option for patients with locally advanced, resectable gastric or GEJ adenocarcinoma. Clinical trial information: NCT04250948 .