Neoadjuvant serplulimab plus nab-paclitaxel and SOX in locally advanced gastric or gastroesophageal junction adenocarcinoma: An interim analysis of a multicenter, randomized, double-blind, phase II trial.

Abstract

e16131 Background: Despite standard neoadjuvant chemotherapy and radical resection, patients with locally advanced gastric cancer (GC) face a high risk of recurrence and poor long-term survival. Although intensified chemotherapy with nab-paclitaxel plus SOX has shown improved tumor regression, pathological responses remain limited. Whether adding immunotherapy can further enhance pathological benefit while preserving surgical feasibility remains unclear. This trial evaluated the efficacy and safety of serplulimab, a PD-1 inhibitor, combined with nab-paclitaxel and SOX as neoadjuvant therapy under close safety monitoring. Methods: This multicenter, randomized, double-blind controlled trial enrolled patients with pathologically confirmed locally advanced GC or gastroesophageal junction (GEJ) adenocarcinoma and an ECOG performance status of 0-1. Patients were assessed by a multidisciplinary team as having potential for R0 resection, but upfront surgery was deemed technically challenging. Patients were randomized to receive 3 cycles of neoadjuvant serplulimab plus nab-paclitaxel and SOX (immunochemotherapy) or placebo plus nab-paclitaxel and SOX (chemotherapy), followed by curative-intent gastrectomy with D2 lymphadenectomy. The primary endpoints were pathological complete response (pCR) and safety. Secondary endpoints included major pathological response (MPR), R0 resection rate. Results: A total of 98 patients were screened, and 51 eligible patients (median age, 62 years) were enrolled and randomized to the immunochemotherapy (n = 23) or chemotherapy (n = 28) group. All patients received surgery after neoadjuvant. The pCR rate was significantly higher in the immunochemotherapy group than in the chemotherapy group (30.4% vs 3.6%; P = 0.025), as was the numerically higher MPR rate (39.1% vs 17.9%; P = 0.090). The R0 resection rate was comparable between the two groups (100.0% vs. 92.9%), while a significantly higher rate of postoperative N downstaging was observed in the immunochemotherapy group (78.3% vs 46.4%; P = 0.021). The incidence of grade 3-4 adverse events (AEs) was 19.6% (n = 10), with a comparable safety profile between the two groups. No grade 5 toxicity was observed. Crucially, AEs were manageable and did not delay neoadjuvant treatment or postponement of surgery in either group. Conclusions: Neoadjuvant serplulimab combined with an intensified regimen of nab-paclitaxel and SOX showed promising efficacy in fit patients with locally advanced GC/GEJ adenocarcinoma. This strategy significantly improved pCR rates and promoted nodal downstaging, with a safety profile that did not compromise surgical feasibility. The study is ongoing; long-term follow-up and exploratory analyses are required to further evaluate the durability and full potential of this strategy. Clinical trial information: NCT06576921 .