FDA

Nivolumab plus ipilimumab OK’d for hepatocellular carcinoma

April 15, 2025

FDA approved nivolumab (Opdivo) with ipilimumab (Yervoy) for the first-line treatment of adults with unresectable or metastatic hepatocellular carcinoma (HCC).

Efficacy

Efficacy was evaluated in the randomized, open-label CHECKMATE-9DW trial (NCT04039607) involving 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 randomized to receive either nivolumab 1 mg/kg as an IV infusion with ipilimumab 3 mg/kg IV q3wks for a maximum of 4 doses, followed by single agent nivolumab 480 mg IV q4wks, or investigator’s choice of lenvatinib or sorafenib.

The primary efficacy outcome measure was overall survival (OS) in all randomized patients. Overall response rate (ORR) was an additional efficacy outcome measure. Median OS was 23.7 months (95% confidence interval [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).

Safety

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

Recommended dose

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.

Sources:

FDA approves nivolumab with ipilimumab for unresectable or metastatic hepatocellular carcinoma. [News release]. 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-ipilimumab-unresectable-or-metastatic-hepatocellular-carcinoma