Nivolumab with ipilimumab is approved by the USFDA for unresectable or metastatic hepatocellular carcinoma

On April 11, 2025, the Food and Drug Administration sanctioned nivolumab (Opdivo, Bristol Myers Squibb Company) in conjunction with ipilimumab (Yervoy, Bristol Myers Squibb Company) for the first treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC).

Effectiveness and Safety

The effectiveness was evaluated in CHECKMATE-9DW (NCT04039607), a study where 668 people with inoperable or advanced liver cancer (HCC) were randomly assigned to two groups. Patients had a confirmed diagnosis of hepatocellular carcinoma (HCC), were in Child-Pugh Class A, had an Eastern Cooperative Oncology Group (ECOG) performance level of 0 or 1, and had not received any previous systemic treatment for their advanced disease.

Patients were randomly assigned to get either nivolumab 1 mg/kg through an IV along with ipilimumab 3 mg/kg IV every 3 weeks for up to 4 doses, then continue with nivolumab 480 mg IV every 4 weeks, or the doctor’s choice of lenvatinib or sorafenib.

The principal effectiveness outcome measure was overall survival (OS) among all randomized participants. The overall response rate (ORR), which was assessed by a separate review team using RECIST 1.1 guidelines, was another measure of how effective the treatment was. The average time patients lived (OS) was 23.7 months for the nivolumab + ipilimumab group and 20.6 months for the lenvatinib or sorafenib group, with a hazard ratio of 0.79 and a p-value of less than 0.0180. The overall response rate (ORR) was 36.1% (95% CI: 31.0, 41.5) in one arm and 13.2% (95% CI: 9.8, 17.3) in the other arm (p-value <0.0001).

The predominant adverse effects (>20%) included rash, pruritus, tiredness, and diarrhea.

The recommended dose of nivolumab is 1 mg for every kilogram of body weight, given together with ipilimumab at 3 mg per kilogram through an IV every three weeks for up to four doses. Following this, administer nivolumab at a dose of 240 mg via an IV every two weeks, or 480 mg through an IV alone every four weeks.