Multinational phase 1-2 trial of nivolumab plus cabozantinib with or without ipilimumab for advanced hepatocellular carcinoma

Until recently, first-line treatment options for advanced hepatocellular carcinoma (aHCC) were the kinase inhibitor sorafenib and lenvatinib, resulting in median overall survival (OS) of 12.3 and 13.6 months, respectively. Cohort 6 of the multinational phase 1-2 CheckMate 040 trial evaluated the doublet and triplet therapies of nivolumab-cabozantinib with or without ipilimumab for aHCC in patients who were treatment-naïve, sorafenib-intolerant, or had progressed on sorafenib. The median progression-free survival was 5.3 and 4.3 months with the doublet and triplet combinations, respectively, while the median overall survival was 20.2 and 22.1 months. The safety profiles were consistent with those established for the individual drugs, with treatment-related adverse events leading to discontinuation in 11% and 23% of patients in the doublet and triplet arms, respectively.