FDA approves nivolumab and ipilimumab for advanced liver cancer

On April 11, 2025, the Food and Drug Administration (FDA) granted approval to nivolumab (Opdivo) and ipilimumab (Yervoy), both products of Bristol Myers Squibb Company, for the initial treatment of adult patients diagnosed with unresectable or metastatic hepatocellular carcinoma (HCC). Details regarding the full prescribing information for Opdivo are expected to be available on the Drugs@FDA website.

The approval was based on the results from the CHECKMATE-9DW study (NCT04039607), a randomized, open-label clinical trial involving 668 adult participants with either unresectable or metastatic HCC. All patients had histologically confirmed HCC, were classified as Child Pugh Class A, and had an ECOG performance status of 0 or 1. Importantly, these individuals had not received any previous systemic treatment for advanced disease.

Participants in the trial were assigned randomly to two groups: one group received nivolumab at a dose of 1 mg/kg combined with ipilimumab at a dose of 3 mg/kg, both administered intravenously every three weeks for up to four doses, followed by a maintenance dose of nivolumab at 480 mg intravenously every four weeks. The other group received a treatment chosen by investigators, either lenvatinib or sorafenib.

The main measure of efficacy in this study was overall survival (OS) among all participants. An additional measure of effectiveness was the overall response rate (ORR), assessed according to RECIST 1.1 criteria by a blinded independent central review. Results showed a median OS of 23.7 months for patients receiving nivolumab and ipilimumab, compared to 20.6 months for those receiving lenvatinib or sorafenib. The hazard ratio was 0.79, indicating a statistically significant improvement in survival for the nivolumab and ipilimumab group, with a p-value of less than 0.0180. In terms of ORR, the nivolumab and ipilimumab group showed a rate of 36.1%, significantly higher than the 13.2% observed in the alternative treatment group, with a p-value of less than 0.0001.

Common adverse reactions observed in more than 20% of patients included rash, pruritus, fatigue, and diarrhea. The recommended dosing schedule involves administering nivolumab at 1 mg/kg with ipilimumab at 3 mg/kg intravenously every three weeks for up to four doses. After this initial treatment, nivolumab should be given at 240 mg intravenously every two weeks or 480 mg as a single agent every four weeks.

This approval process was part of Project Orbis, an initiative by the FDA's Oncology Center of Excellence that supports simultaneous submission and review of oncology drugs across international partners. For this particular review, the FDA worked in collaboration with Health Canada and Switzerland’s Swissmedic. The application is still under review by other regulatory bodies.

The approval benefited from the Real-Time Oncology Review (RTOR) pilot program, which allows for data submission before the complete clinical application is filed. Additionally, the Assessment Aid, a voluntary submission from the applicant, facilitated the FDA’s evaluation process. This application was granted orphan drug designation, reflecting its significance in addressing serious conditions.

Professionals in the healthcare field are encouraged to report any severe adverse events potentially linked to the use of any medication or device through the FDA’s MedWatch Reporting System.