Neoadjuvant serplulimab with concurrent chemoradiotherapy in resectable esophagogastric junction adenocarcinoma: Phase 2 updated results.

Abstract

2612 Background: This study evaluated the efficacy and safety of neoadjuvant Serplulimab combined with concurrent chemoradiotherapy for locally advanced resectable esophagogastric junction (EGJ) adenocarcinoma. Methods: Eligible patients with resectable EGJ（cT3-4 or N+M0）adenocarcinoma received neoadjuvant Serplulimab (300 mg) plus SOX (oxaliplatin 130 mg/㎡; TS1 40-60 mg) for the first cycle, followed by Serplulimab with concurrent chemoradiotherapy (oxaliplatin 100 mg/㎡, TS1 40-60 mg; radiotherapy dose 45 Gy/ 25 fractions) during the second and third cycles. Surgery was performed 6-8 weeks after chemoradiotherapy. Tissue and blood samples were collected for genetic analysis. Primary endpoints included pathological complete response (pCR) and major pathological response (MPR). Results: From March 2023 to November 2024, 24 patients were enrolled and 19 patients underwent radical resection. The R0 rate was 100%. pCR rate was 26.3%, MPR rate was 36.8%. T downstaging rate 78.9%, ypN0 89.5%. The median DFS was not reached. Microsatellite stable status was 100%. PD-L1 CPS expression: < 1 (5.3%), 1-5 (42%), > 5 (52.6%), > 10 (31.6%). PD-L1 expression was associated with pathological response, with MPR rates of 57.1% for CPS ≥5 and 14.3% for CPS < 5. Minimal residual disease positivity (MDR+) before enrollment was 68.7%, and 6 MRD+ patients converted to MRD- after neoadjuvant therapy. Grade ≥3 adverse events occurred in 33.3% of patients, with manageable treatment-related adverse events. Conclusions: Neoadjuvant Serplulimab with concurrent chemoradiotherapy showed promising efficacy for locally advanced resectable EGJ adenocarcinoma. Improved R0 and ypN0 rate may change the surgical procedure in the future. Follow-up will assess correlations between biomarkers and outcomes. Clinical trial information: NCT05918419 .