Surufatinib plus toripalimab in patients with advanced solid tumors: a single-arm, open-label, phase 1 trial.

PURPOSE: This phase 1 trial evaluated the safety, preliminary efficacy, and pharmacokinetics of surufatinib, a small molecular tyrosine kinase inhibitor, combined with toripalimab, a programmed cell death protein-1 antibody, in patients with advanced solid tumors.

METHODS

This is an open-label, dose-escalation and expansion study in patients with solid tumors who had failed standard therapies or had no effective treatment. In the dose-escalation stage, patients were treated with surufatinib, at dose levels of 200, 250, or 300 mg once daily (QD) in combination with toripalimab 240 mg, every 3 weeks (Q3W), to estimate maximum tolerated dose. Additional patients were enrolled in the dose expansion stage to further assess the efficacy, safety, and pharmacokinetics profile. Recommended phase 2 dose (RP2D) was determined based on the safety, tolerability, and preliminary efficacy from dose-escalation and expansion stages.

RESULTS

From Feb 14, 2019 to Dec 20, 2020, 33 patients were screened, of which 30 patients were enrolled. One patient in the 300 mg cohort experienced dose limited toxicity, a grade 3 hyperthyroidism. The most frequent treatment-related adverse events of grade ≥ 3 were hypertension (20.0%), transaminases increased (13.3%), and blood bilirubin increased (13.3%). No treatment-related death or treatment discontinuation was identified. The RP2D was determined to be surufatinib 250 mg QD plus toripalimab 240 mg Q3W. Objective response rate was 24.1% (95% confidence interval 10.3‒43.5%) in this study.

CONCLUSIONS

Surufatinib plus toripalimab was well tolerated, with no unexpected safety signals, and showed preliminary anti-tumor activity in patients with advanced solid tumors.

TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03879057; registration date: March 18, 2019.