CapeOX (capecitabine and oxaliplatin) combined with sintilimab and bevacizumab biosimilar (IBI305) for first-line treatment of advanced gastric or oesophagogastric junction adenocarcinoma: study protocol for a single-arm, phase Ib/II trial

BACKGROUND: A combination of chemotherapy and immune checkpoint inhibitor therapy has been demonstrated to be effective as a first-line treatment of gastric or gastro-oesophageal junction (G/GEJ) cancer. The conventional treatment strategy for patients with advanced/metastatic human epidermal growth factor receptor 2-negative G/GEJ cancer is recommended. However, the response rate and enhancements in survival are still significantly insufficient. The present study will investigate the efficacy and safety of incorporating a bevacizumab biosimilar IBI305 into chemotherapy and immunotherapy as a first-line treatment for advanced or metastatic G/GEJ cancer. METHODS AND ANALYSIS: This single-arm, open-label, prospective phase Ib/II clinical study will involve 57 participants. In phase Ib of the trial, patients with advanced or metastatic G/GEJ cancer will receive capecitabine and oxaliplatin (CapeOX) together with sintilimab (200 mg intravenously every 3 weeks) and IBI305 (7.5, 10 or 15 mg/kg intravenously every 3 weeks) in a 3+3 dose-escalation design to evaluate dose-limiting toxicities (DLTs) within 6 weeks of treatment initiation. In phase II, the patients will receive CapeOX combined with sintilimab and IBI305 at the recommended phase II dose. The primary objectives will be to assess DLTs (phase Ib) and the objective response rate (phase II). The secondary objectives will include progression-free survival, overall survival, disease control rate, duration of response, adverse effects, quality of life and safety. ETHICS AND DISSEMINATION: The trial protocol was approved by the Ethics Committee of West China Hospital and ClinicalTrials. The final results will be published in a peer-reviewed journal upon completion of the study. TRIAL REGISTRATION NUMBER: NCT05640609.