Perioperative PD-1 antibody toripalimab plus SOX or XELOX chemotherapy versus SOX or XELOX alone for locally advanced gastric or gastro-oesophageal junction cancer: Results from a prospective, randomized, open-label, phase II trial

4001 Background: The combination of PD-1 antibody and chemotherapy was shown to be effective in advanced gastric or gastro-oesophageal junction (GEJ) cancer, but has not yet been investigated in the context of locally advanced patients. In this study, we conducted a prospective, randomized, open-label phase II trial to evaluate the effectiveness of adding PD-1 antibody to perioperative chemotherapy in patients with locally advanced resectable gastric or GEJ cancer. Methods: In this randomized, open-label, phase II study, patients with resectable gastric or GEJ cancer clinically staged as cT3-4a N+M0 were randomized (1:1) to three preoperative and five postoperative 3-week cycles of SOX/XELOX (C arm) or PD-1 antibody toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for 6 months (C+T arm). The primary endpoint was pathological complete regression/moderate regression rate (TRG 0/1). The secondary endpoints were pathological complete response (pCR), R0 resection rate, recurrence-free survival, event-free survival, objective response rate, disease control rate, overall survival and treatment safety. The study had been completed enrollment, and here, we analyzed the primary endpoint. Mantel-Haenszel test was used to test the difference of pathological regression between the two arms. The trial was registered at ClinicalTrials.gov, identifier: NCT04250948. Results: Between Oct 2019 and June 2022, 108 patients (C+T arm, n=54; C arm, n=54) were enrolled and assessed using intention-to-treat analysis. Patients in the toripalimab plus chemotherapy arm achieved higher proportion of TRG 0/1 than those in the chemotherapy arm (44.4% [24/54, 95% CI: 30.9%-58.6%] vs 20.4% [11/54, 95% CI: 10.6%-33.5%]; P=0.009). A higher pCR rate was observed in the C+T arm (24.1% [13/54, 95% CI:13.5%-37.6%] vs 9.3% [5/54, 95% CI: 3.1%-20.3%]; P=0.039). Preoperative therapies (3 cycles) were completed in 96.3% of patients and postoperative cycles (>3 cycles) in 81.5%, with no significant differences observed between these two arms. A higher proportion of downstaging was observed in the C+T arm (ypT0-2: 46.3% vs 22.2% [P=0.002]; ypstage 0-1: 38.9% vs 16.7% [P=0.024]). Surgical morbidity (11.8% in the C+T arm vs 13.5% in the C arm) and mortality (1.9% vs 0%) and treatment-related grade 3-4 adverse events (27.8% vs 25.9%) were comparable between the arms. Conclusions: Perioperative PD-1 antibody toripalimab plus chemotherapy demonstrated a significantly improved pathological regression and might be a promising option for patients with locally advanced resectable gastric or GEJ cancer. Clinical trial information: NCT04250948 .