Sintilimab plus Bevacizumab biosimilar IBI305 and chemotherapy as a first-line treatment in advanced gastric or gastroesophageal junction adenocarcinoma (SBAGA): a single-arm, phase Ib/II study.

Adding anti-PD-1 or anti-VEGF therapy to chemotherapy improves survival in patients with advanced gastric cancer, yet outcomes remain poor. This Phase Ib/II trial aimed to evaluate the efficacy and safety of combining sintilimab, the bevacizumab biosimilar IBI305, and CapeOX chemotherapy as a first-line treatment for patients with HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma (GA/GEJA). In phase Ib, no dose-limiting toxicities (DLTs) that served as the primary endpoint were observed (N = 9). In phase II, the primary endpoint of the objective response rate (ORR) in the efficacy-evaluable population (N = 54) was 87.0% (95% CI: 75.1-94.6%), achieving the pre-specified target was reached. Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DoR), and safety. The DCR was 98.1% (95% CI: 90.1-100.0%). At a median follow-up of 20.3 months, median PFS and DoR were 12.2 months (95% CI: 9.2-18.1) and 12.5 months (95% CI: 9.4-NE), respectively, while the median OS was not reached. A clinical benefit was observed regardless of PD-L1 CPS, Claudin-18.2 expression status, or the presence of peritoneal metastases. Treatment-related adverse events of grade ≥3 occurred in 66% of patients; the most common were neutropenia (14%), fatigue (13%), and thrombocytopenia (11%). The limitations of the study include the single-arm, non-randomized design and the modest sample size, which necessitate confirmation in larger randomized controlled trials. Nonetheless, sintilimab plus IBI305 and chemotherapy demonstrated promising antitumor activity and favorable PFS with manageable toxicity in HER2-negative advanced GA/GEJA. Trial number: NCT05640609.