Neoadjuvant serplulimab in combination with chemotherapy for locally advanced gastric or gastro-esophageal junction cancer.

4030 Background: Perioperative therapy combined with surgery is the standard treatment for locally advanced gastric or gastro-esophageal junction (G/GEJ) cancer; however, long-term survival remains suboptimal. Immunotherapy has demonstrated antitumor activity and an acceptable safety profile in advanced G/GEJ cancer. This study aimed to evaluate the efficacy and safety of neoadjuvant Serplulimab, a PD-1 inhibitor, in combination with chemotherapy in previously untreated, locally advanced G/GEJ cancer. Methods: Eligible patients with resectable G/GEJ adenocarcinoma staged as cT3-4aN+M0 were enrolled. The treatment regimen included Serplulimab (300 mg on day 1, every 3 weeks [Q3W]) plus SOX chemotherapy (oxaliplatin 130 mg/㎡on day 1; and S-1 60 mg twice daily on days 1-14, Q3W) for three cycles. Following the preoperative treatment, patients underwent surgery 6-8 weeks after the therapy. The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints included major pathological response (MPR) rate, R0 resection rate, disease-free survival (DFS), overall survival (OS), and toxicity. Results: From October 13, 2023, to December 31, 2024, 25 patients were enrolled, all of whom completed neoadjuvant therapy and underwent radical surgical. The R0 resection rate was 100%. Five patients achieved pCR (pCR rate: 20%), and an additional five patients achieved MPR (MPR rate: 40%). Median DFS and OS were not reached. Safety analysis included all patients who received at least one cycle of neoadjuvant therapy. The most common treatment-related adverse events (TRAEs) of any grade included nausea, anorexia, thrombocytopenia, fatigue, and thyroid dysfunction. No grade ≥3 TRAEs were observed. Conclusions: Neoadjuvant Serplulimab combined with SOX chemotherapy demonstrated promising efficacy and a favorable safety profile in patients with locally advanced, resectable G/GEJ adenocarcinoma. These findings support the potential role of immune-based neoadjuvant therapy in this setting.