Purpose: To investigate the safety and efficacy of nivolumab plus cabozantinib with or without ipilimumab in patients with advanced hepatocellular carcinoma.
Methods: In cohort 6 of the multicohort, open-label, phase I/II CheckMate 040 study, patients who were treatment-naive, sorafenib-intolerant, or had progressed on sorafenib were randomly assigned 1:1 to nivolumab 240 mg once every 2 weeks plus cabozantinib 40 mg once daily (doublet arm); or nivolumab 3 mg/kg every 2 weeks plus cabozantinib 40 mg once daily with ipilimumab 1 mg/kg once every 6 weeks (triplet arm). Primary objectives were safety and tolerability, objective response rate, and duration of response by investigator assessment per RECIST v1.1. Secondary objectives included progression-free survival (by blinded independent central review) and overall survival.
Results: Seventy-one patients were randomly assigned: 36 to the doublet arm and 35 to the triplet arm. After 32.0-month median follow-up, objective response rate (95% CI) was 17% (6 to 33) and 29% (15 to 46) in the doublet and triplet arms, respectively. Median (95% CI) duration of response was 8.3 (6.9 to not estimable) months in the doublet arm and not reached (0.0 to not estimable) in the triplet arm. Median progression-free survival was 5.1 and 4.3 months, and median overall survival was 20.2 and 22.1 months for the doublet and triplet arms, respectively. Grade 3-4 treatment-related adverse events occurred in 50% and 74% of patients and treatment-related adverse events leading to discontinuation were reported for 11% and 23% in the doublet and triplet arms, respectively. There were no treatment-related deaths in either arm.
Conclusion: Nivolumab plus cabozantinib with or without ipilimumab showed encouraging preliminary antitumor activity and had consistent safety profiles with those established for the individual drugs in patients with advanced hepatocellular carcinoma.
Trial registration: ClinicalTrials.gov NCT01658878.