Anti-PD-1 antibody SHR-1210 plus apatinib for metastatic colorectal cancer: a prospective, single-arm, open-label, phase II trial

In the REGONIVO study, regorafenib combined with nivolumab was effective in the treatment of microsatellite stable (MSS) metastatic colorectal cancer (mCRC), which indicated anti-angiogenic drugs may enhance the efficacy of immune checkpoint inhibitors. Therefore, we designed a single-arm, single-center, open-label, phase II trial to determine the toxicity and efficacy of SHR-1210 (an anti-PD-1 antibody) plus apatinib in MSS mCRC. The sample size was estimated using a Simon Optimum two stage design. 10 patients were included at the first stage and if one effective patient observed, an additional 19 patients would be added. Patients with MSS mCRC who refractory to second-line treatment or intolerant to standard treatment were given SHR-1210 200 mg every 2 weeks and apatinib 250-375 mg once daily until unacceptable toxicity or disease progression occurred. In our study, the objective response rate was 0% and the disease control rate was 22.2%. The median progression-free survival was 1.83 months (95% confidence interval (CI) 1.80-1.86 months), and the median overall survival was 7.80 months (95% CI 0-17.07). Treatment-related adverse events (AEs) occurred in all patients (100%). The most common treatment-related AEs were hypertension and proteinuria (70% each). Grade 3 AEs were observed in nine patients (9/10, 90%), and the commonest was hypertension (30%). In conclusion, SHR-1210 combined with apatinib has failed to improve the efficacy of treatment of MSS mCRC, and the intolerable toxicity may be the leading cause.