On April 11, 2025, the Food and Drug Administration approved nivolumab with ipilimumab for the first-line treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC).

Full prescribing information for nivolumab will be posted on Drugs@FDA.

Efficacy and Safety

Efficacy was evaluated in CHECKMATE-9DW (NCT04039607), a randomised (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 randomised to receive either nivolumab 1 mg/kg as an intravenous (IV) infusion with ipilimumab 3 mg/kg IV every 3 weeks for a maximum of 4 doses, followed by single agent nivolumab 480 mg IV every 4 weeks, or investigator’s choice of lenvatinib or sorafenib.

The primary efficacy outcome measure was overall survival (OS) in all randomised patients. Overall response rate (ORR) based on RECIST 1.1 criteria, assessed by blinded independent central review, was an additional efficacy outcome measure. Median OS was 23.7 months (95% CI: 18.8, 29.4) in the nivolumab + ipilimumab arm and 20.6 months (95% CI: 17.5, 22.5) in the lenvatinib or sorafenib arm (Hazard Ratio 0.79 [95% CI: 0.65, 0.96] p-value <0.0180. ORR was 36.1% (95% CI: 31.0, 41.5) and 13.2% (95% CI: 9.8, 17.3) in the respective arms (p-value <0.0001).

The most common adverse reactions (>20%) were rash, pruritus, fatigue, and diarrhoea.

The recommended nivolumab dose is 1 mg/kg with ipilimumab 3 mg/kg intravenously every three weeks for a maximum of four doses, followed by nivolumab 240 mg IV every 2 weeks or nivolumab 480 mg IV as a single agent every 4 weeks.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with Health Canada and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies.

Source: FDA