On April 11, 2025, the U.S. Food and Drug Administration approved nivolumab (Opdivo) with ipilimumab (Yervoy) for the first-line treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC).
Efficacy was evaluated in CheckMate-9DW (ClinicalTrials.gov identifier NCT04039607), a randomized (1:1), open-label trial in 668 adults with unresectable or metastatic HCC. Patients had histologically confirmed HCC, Child Pugh Class A, ECOG performance status 0 or 1, and no prior systemic therapy for advanced disease. Patients were randomly assigned to receive either nivolumab at 1 mg/kg as an intravenous (IV) infusion with ipilimumab at 3 mg/kg IV every 3 weeks for a maximum of 4 doses, followed by single-agent nivolumab at 480 mg IV every 4 weeks, or investigator’s choice of lenvatinib or sorafenib.
The primary efficacy outcome measure was overall survival in all randomized patients. Overall response rate based on RECIST 1.1 criteria, assessed by blinded independent central review, was an additional efficacy outcome measure. Median overall survival was 23.7 months (95% confidence interval [CI] = 18.8–29.4) in the nivolumab plus ipilimumab arm and 20.6 months (95% CI = 17.5–22.5) in the lenvatinib or sorafenib arm (hazard ratio [HR] = 0.79; 95% CI = 0.65–0.96; P < .0180). Overall response rate was 36.1% (95% CI = 31.0–41.5) and 13.2% (95% CI = 9.8–17.3) in the respective arms (P < .0001).
The most common adverse reactions (> 20%) were rash, pruritus, fatigue, and diarrhea.
The recommended dose is nivolumab at 1 mg/kg with ipilimumab at 3 mg/kg intravenously every 3 weeks for a maximum of 4 doses, followed by nivolumab at 240 mg IV every 2 weeks or nivolumab at 480 mg IV as a single agent every 4 weeks.
