Phase II trial of efficacy, safety and biomarker analysis of sintilimab plus anlotinib for patients with recurrent or advanced endometrial cancer

BACKGROUND: Although co-inhibition of the angiogenesis and programmed death 1 (PD-1) pathways is proposed as an effective anticancer strategy, studies in Chinese patients with endometrial cancer are sufficient. Anlotinib is an oral multi-targeted tyrosine kinase inhibitor affecting tumor angiogenesis and proliferation; sintilimab is an anti-PD-1 monoclonal antibody. METHODS: This was a phase II trial using Simon’s two-stage design. This study enrolled patients with endometrial cancer who had progressed after platinum-based chemotherapy. Sintilimab 200 mg was administered intravenously on day 1 every 3 weeks, and anlotinib 12 mg was administered on days 1–14 in a 21-day cycle. The primary endpoint was the objective response rate (ORR) using the immune-related Response Evaluation Criteria in Solid Tumors criteria. Immunohistochemistry and whole-exome sequencing were used as correlative investigations. RESULTS: Between November 2019 and September 2020, 23 eligible patients were enrolled. The ORR and disease control rates were 73.9% (95% CI, 51.6 to 89.8) and 91.3% (95% CI, 72.0 to 98.9), respectively, with 4 complete and 12 partial responses. With a median follow-up of 15.4 months (95% CI, 12.6 to 18.3), the median progression-free survival was not reached, and the probability of PFS >12 months was 57.1% (95% CI, 33.6 to 75.0). Exploratory analysis revealed that mutations in the homologous repair pathway showed a trend for higher ORR (100% vs 0%, p=0.07). Treatment-related grade 3/4 adverse events were observed in 50.0% of the patients. CONCLUSIONS: Sintilimab plus anlotinib demonstrated robust therapeutic benefits with tolerable toxicity in endometrial cancer. TRIAL REGISTRATION NUMBER: NCT04157491.