Nivolumab and Ipilimumab Approved for Advanced Hepatocellular Carcinoma
Expert Perspectives · Lyn Brook · 2025-04-14
The FDA has approved nivolumab (Opdivo®, Bristol Myers Squibb) in combination with ipilimumab (Yervoy®, Bristol Myers Squibb) for the first-line treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC).
Why This Approval Matters
The approval of nivolumab and ipilimumab as a first-line treatment for advanced HCC represents a significant advancement in the management of this challenging disease. By combining two immune checkpoint inhibitors, this regimen offers improved survival outcomes and higher response rates compared to standard tyrosine kinase inhibitor therapies.
Breaking Down the CheckMate 9DW Trial
The efficacy of nivolumab and ipilimumab was evaluated in the CheckMate 9DW trial (NCT04039607), an open-label, phase 3 study. The trial enrolled 668 adults with histologically confirmed HCC, Child-Pugh Class A liver function, and an ECOG performance status of 0 or 1. None of the patients had received prior systemic therapy for advanced disease.
Patients were randomized 1:1 to receive either nivolumab 1 mg/kg with ipilimumab 3 mg/kg intravenously every three weeks for a maximum of four doses, followed by nivolumab 480 mg every four weeks, or the investigator’s choice of lenvatinib or sorafenib.
Key efficacy end points included overall survival (OS) and overall response rate (ORR). Results demonstrated:
- Median OS: 23.7 months in the nivolumab plus ipilimumab arm versus 20.6 months in the lenvatinib or sorafenib arm
- ORR: 36.1% in the nivolumab plus ipilimumab arm compared to 13.2% in the lenvatinib or sorafenib arm
Managing Adverse Events
The safety profile of nivolumab and ipilimumab was consistent with previous studies of these agents. The most common adverse experienced by ≥20% of patients included rash, pruritus, fatigue, and diarrhea.
Clinical Implications and Future Outlook
Nivolumab plus ipilimumab demonstrated statistically significant OS benefit versus lenvatinib/sorafenib in patients with previously untreated unresectable HCC, as well as higher ORR and durable responses with a manageable safety profile,” concluded Peter Galle, MD, PhD Professor at the University Medical Center Mainz, in Mainz, Germany, and colleagues, in their published results of the CheckMate 9DW trial. “These results support this combination as a potential new first-line standard of care for unresectable HCC.”
Dosing and Administration
The recommended dosing regimen begins with nivolumab 1 mg/kg and ipilimumab 3 mg/kg intravenously every three weeks for a maximum of four doses. After the induction phase, patients transition to maintenance therapy with nivolumab as a single agent, administered at 240 mg every two weeks or 480 mg every four weeks.