FDA approves nivolumab with ipilimumab for unresectable or metastatic hepatocellular carcinoma

Regulatory approval: On April 11, 2025, the FDA approved nivolumab plus ipilimumab for first-line treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC). Approval was supported by the phase 3 CHECKMATE-9DW trial, which reported median overall survival of 23.7 months with nivolumab/ipilimumab vs 20.6 months with lenvatinib or sorafenib (HR 0.79; 95% CI 0.65–0.96; p<0.0180) and ORR 36.1% vs 13.2% (p<0.0001).

FDA approval (2025-04-11): nivolumab + ipilimumab in unresectable/metastatic HCC

The FDA approved nivolumab (Opdivo) with ipilimumab (Yervoy) on April 11, 2025 for first-line treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC).

Supporting evidence: CHECKMATE-9DW

Efficacy and safety were evaluated in CHECKMATE-9DW (NCT04039607), a randomized (1:1), open-label trial in 668 adults with unresectable or metastatic HCC. Key eligibility included histologically confirmed HCC, Child-Pugh A, ECOG 0–1, and no prior systemic therapy for advanced disease.

Patients received either:

  • Nivolumab 1 mg/kg IV + ipilimumab 3 mg/kg IV every 3 weeks (maximum 4 doses), then nivolumab 480 mg IV every 4 weeks, or
  • Investigator’s choice of lenvatinib or sorafenib.

Primary endpoint: overall survival (OS). Additional endpoint: ORR by RECIST 1.1 via blinded independent central review.

  • Median OS: 23.7 months (95% CI 18.8–29.4) vs 20.6 months (95% CI 17.5–22.5); HR 0.79 (95% CI 0.65–0.96); p<0.0180.
  • ORR: 36.1% (95% CI 31.0–41.5) vs 13.2% (95% CI 9.8–17.3); p<0.0001.

Safety and dosing (per FDA communication)

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

Recommended regimen: nivolumab 1 mg/kg with ipilimumab 3 mg/kg IV q3w (max 4 doses), followed by nivolumab 240 mg q2w or 480 mg q4w.

The review was conducted under Project Orbis with collaboration with Health Canada and Swissmedic; reviews at other agencies were ongoing at the time of the FDA announcement.

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