Feasibility and tolerability of sintilimab plus anlotinib as the second‐line therapy for patients with advanced biliary tract cancers: An open‐label, single‐arm, phase II clinical trial

Patients with biliary tract cancer (BTC) were associated with poor prognosis and limited therapeutic options after first‐line therapy currently. In this study, we sought to evaluate the feasibility and tolerability of sintilimab plus anlotinib as the second‐line treatment for patients with advanced BTC. Eligible patients had histologically confirmed locally advanced unresectable or metastatic BTC and failed after the first‐line treatment were recruited. The primary endpoint was overall survival (OS). Simultaneously, association between clinical outcomes and genomic profiling and gut microbiome were explored to identify the potential biomarkers for this regimen. Twenty patients were consecutively enrolled and received study therapy. The trail met its primary endpoint with a median OS of 12.3 months (95% CI: 10.1‐14.5). Only four (20%) patients were observed of the grade 3 treatment‐related adverse events (TRAEs) and no grade 4 or 5 TRAEs were detected. Mutation of AGO2 was correlated with a significantly longer OS. Abundance of Proteobacteria was associated with inferior clinical response. Therefore, sintilimab plus anlotinib demonstrated encouraging anti‐tumor activity with a tolerable safety profile and deserved to be investigated in larger randomized trials for patients with advanced BTC subsequently. What's new? The clinical benefits of the combination of immune checkpoint inhibitors and anti‐angiogenic agents have been demonstrated for a variety of solid tumors. However, data on the feasibility and safety of PD‐1 blockade plus anti‐angiogenic tyrosine kinase inhibitors in patients with previously treated advanced biliary tract cancer remains scarce. In this phase II clinical trial, the combination of sintilimab plus anlotinib showed encouraging anti‐tumor activity and a manageable safety profile in patients with advanced biliary tract cancer, representing a potential, chemotherapy‐free option for second‐line treatment. Enrichment of the gut microbiome in Proteobacteria was associated with inferior clinical response.