Gastric cancer is one of the most common malignant tumors with the highest mortality in the world. Post-line treatment options for metastatic gastric cancer (mGC) are limited. Monoclonal antibodies targeting Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) and small molecule tyrosine kinase inhibitors (TKIs) have shown benefits on progression free survival (PFS) and overall survival (OS) in second-line or third-line treatment of mGC. Following a phase III randomized clinical trial, apatinib, an oral small-molecule drug targeted with VEGFR-2, has been proved to significantly prolong patients' OS in the third-line or later-line treatment of mGC, thus becoming the standard third-line or later-line regimen for gastric cancer in China. In immunotherapy of mGC, pembrolizumab has been approved for third-line treatment of programmed cell death-Ligand 1 (PD-L1) positive advanced gastric cancer, and nivolumab also become the standard third-line treatment regimen. What is the best option for third-line treatment of metastatic gastric cancer remains unclear. Analysis from the subgroup of the Attraction 2 study showed that patients who had previously been treated with anti-VEGFR targeted drug ramucizumab had significantly higher PFS and OS than those who had not. The REGONIVO study also showed that the anti-angiogenic TKI regorafenib combined with nivolumab achieved a good objective response rate after the failure of standard treatment in gastric cancer. Therefore, it is worth exploring whether apatinib combined with anti-PD-1 monoclonal antibody could bring improvements in PFS and OS while compared with apatinib monotherapy. This open, single-center, randomized phase II study was to evaluate the clinical benefit of apatinib plus camrelizumab which is an anti-PD-1 monoclonal antibody, versus apatinib in patients with metastatic gastric cancer refractory to two or more lines of treatment, fully evaluating the efficacy and safety of the combined regimen. A total of 102 patients were planned for enrollment in this study. This trial was expected to start in March 2021, and the end of recruitment will be approximately on March 2024, and the end of follow-up will be approximately on October 2023. The control group would take apatinib monotherapy regimen, with 500mg oral apatinib every day, and the experimental group would take apatinib plus camrelizumab regimen, with 250 mg oral apatinib every day continuously and 200mg intravenous camrelizumab every 14 days. Patients would be assessed every 8 weeks and those patients with disease control would be received the treatment until progressive disease (PD) or intolerable toxicity. The maximum treatment duration of camrelizumab was 2 years.
This open, single-center, randomized phase II study was to evaluate the clinical benefit of apatinib plus camrelizumab which is an anti-Programmed cell death-1 (PD-1) monoclonal antibody, versus apatinib in patients with metastatic gastric cancer refractory to two or more lines of treatment, fully evaluating the efficacy and safety of the combined regimen.