Surufatinib plus toripalimab for patients with advanced solid tumors and disease progression after prior immunotherapy: an open-label multi-cohort phase 2 trial

Immune checkpoint inhibitor (ICI) plus an anti-angiogenic agent has shown antitumor activity in patients whose disease had progressed on a prior ICI but further evidence across tumor types is needed. This phase 2 trial evaluated the efficacy and safety of surufatinib (anti-angiogenic multi-tyrosine-kinase inhibitor, 250 mg orally, once daily) plus toripalimab (programmed-death-1 [PD-1] inhibitor, 240 mg intravenously, once every three weeks) in adult patients with advanced solid tumors and progression on a PD-1/programmed death ligand 1 inhibitor. The primary endpoint was investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A total of 28 patients were enrolled and received treatment. Two of 27 evaluable patients achieved partial response, for an ORR of 7.4% (95% CI: 0.9–24.3); the disease control rate was 66.7% (95% CI: 46.0–83.5). Median progression-free survival was 3.9 months (95% CI: 1.4–4.2) and overall survival was 13.0 months (95% CI: 8.6–21.6; median follow-up: 20.9 months). Efficacy findings were consistent when assessed per immune-related RECIST. Eleven (39.3%) patients experienced grade ≥ 3 treatment-related adverse events (TRAEs), most frequently increased blood pressure (n = 3, 10.7%) and liver damage (n = 2, 7.1%). TRAEs led to surufatinib discontinuation in two (7.1%) patients. There were no treatment-related deaths. ICI-based combination rechallenge with surufatinib-toripalimab conferred signal-generating activity in patients with advanced solid tumors, with a manageable safety profile. Studies in larger populations are warranted.