Capecitabine and Oxaliplatin（CAPEOX） combined with Sintilimab plus bevacizumab biosimilar（IBI305）for first-line treatment of advanced gastric or esophagogastric junction adenocarcinoma: study protocol of a single-arm, phase Ib/II trial

Abstract

Abstract Gastric cancer is the fifth most diagnosed cancer in the world and the third leading cause of cancer-related death. For patients with advanced gastric cancer, systemic treatment combined with immune immune check point Inhibitors is the first choice. However, the median survival time after first-line chemotherapy for advanced gastric cancer is about 15 months, and treatment still faces bottlenecks. Bevacizumab is a humanized monoclonal antibody that inhibits the binding of human VEGF to its receptor. Although AVAGAST did not reach its primary objective, chemotherapy combined with bevacizumab in the AVAGAST study significantly improved the median progression-free survival (mPFS) and objective response rate (ORR) in the first-line treatment of advanced gastric cancer. The combination of chemotherapy with immunotherapy has become the standard treatment for gastric cancer. Furthermore, immunotherapy and bevacizumab have a synergistic effect; hence, whether the addition of bevacizumab to chemotherapy combined with immunotherapy can bring clinical benefits to gastric cancer patients needs to be explored. Methods and analysis This was a single-arm, open-label, prospective Phase 1b/II clinical study involving a total of 57 cases. In Phase 1b, patients with advanced or metastatic stomach adenocarcinoma or esophagogastric junction received CAPEOX (Oxaliplatin and capecitabine) along with sintilimab (200 mg intravenously every 3 weeks) and bevacizumab (7.5, 10, or 15 mg/kg intravenously every 3 weeks) in a 3+3 dose escalation Phase to determine the maximum tolerated dose and dose-limiting toxicities. In Phase 2, patients with advanced gastric or esophagogastric junction adenocarcinoma received CAPEOX plus sintilizumab and bevacizumab. The primary objectives were dose-limiting toxicities (Phase 1b) and ORR (Phase 2). Secondary objectives include PFS, overall survival, disease control rate, duration of response, adverse effects, quality of life, and safety. Ethics and Communication This trial was approved by the Ethics Committee of West China Hospital. The final results of this trial will be published in a peer-reviewed journal upon completion. Trial registration: ClinicalTrials.gov Identifier: NCT05640609. Registration date: December 23, 2022