CheckMate 9DW
Trial question
What is the effect of nivolumab plus ipilimumab in patients with previously untreated unresectable HCC?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
18.0% female
82.0% male
N = 668
668 patients (120 female, 548 male).
Inclusion criteria: adult patients with previously untreated unresectable HCC.
Key exclusion criteria: fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC; previous liver transplantation; episodes of hepatic encephalopathy in the past 12 month; clinically significant ascites; main portal vein invasion and active co-infection with both HBV and HCV or both HBV and HDV.
Interventions
N=335 nivolumab plus ipilimumab (nivolumab 1 mg/kg plus ipilimumab 3 mg/kg IV every 3 weeks for up to 4 doses, followed by nivolumab 480 mg every 4 weeks).
N=333 lenvatinib or sorafenib (investigator's choice of either oral lenvatinib 8 mg or 12 mg mg daily depending on body weight or oral sorafenib 400 mg BID).
Primary outcome
Overall survival
23.7 months
20.6 months
23.7 months
17.8 months
11.8 months
5.9 months
0.0 months
Nivolumab plus
ipilimumab
Lenvatinib or
sorafenib
Significant
increase ▲
Significant increase in overall survival (23.7 months vs. 20.6 months; HR 1.27, 95% CI 1.04 to 1.54).
Secondary outcomes
Significant increase in confirmed objective response (36% vs. 13%; AD 23%, 95% CI 11.51 to 34.49).
Significantly longer median time to first symptom deterioration (2.6 months vs. 2.1 months; HR 1.32, 95% CI 1.08 to 1.61).
Safety outcomes
No significant difference in grade 3-4 treatment-related adverse events.
Conclusion
In adult patients with previously untreated unresectable HCC, nivolumab plus ipilimumab was superior to lenvatinib or sorafenib with respect to overall survival.
Reference
Thomas Yau, Peter R Galle, Thomas Decaens et al. Nivolumab plus ipilimumab versus lenvatinib or sorafenib as first-line treatment for unresectable hepatocellular carcinoma (CheckMate 9DW): an open-label, randomised, phase 3 trial. Lancet. 2025 May 7:S0140-6736(25)00403-9. Online ahead of print.
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