CheckMate 9DW: trial | Bending the Curve: Trial by Trial

CheckMate 9DW

Nivolumab plus ipilimumab versus lenvatinib or sorafenib as first-line treatment for unresectable hepatocellular carcinoma (CheckMate 9DW): an open-label, randomised, phase 3 trial

Phase 3N = 668NCT04039607

Population

Adults with unresectable hepatocellular carcinoma and no previous systemic therapy; at least one measurable untreated lesion (RECIST 1.1), Child-Pugh score 5 or 6, ECOG performance status 0 or 1

Design

Open-label randomised (1:1) phase 3 trial at 163 hospitals and cancer centres in 25 countries; nivolumab plus ipilimumab versus investigator's choice of lenvatinib or sorafenib; randomisation stratified by aetiology, macrovascular invasion and/or extrahepatic spread, and baseline alpha-fetoprotein. Patients had a Child-Pugh score of 5 or 6 and ECOG performance status 0 or 1. Primary endpoint overall survival in all randomly assigned patients; results are from a preplanned interim analysis.

Primary endpoint

Arms

Nivolumab plus ipilimumab (experimental, n = 335): Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for up to four doses, then nivolumab 480 mg every 4 weeks
Lenvatinib or sorafenib (control, n = 333): Investigator's choice of lenvatinib (8 mg or 12 mg daily by bodyweight) or sorafenib 400 mg twice daily

People

Yau T

OSHR 0.79 (95% CI 0.65–0.96)Δ median OS+3.1 monthsΔ 24-month OS+10 points

Show the numbers

Results reported for CheckMate 9DW
Endpoint	Analysis	Nivolumab plus ipilimumab	Lenvatinib or sorafenib	Effect
OSAll randomly assigned patients	interimmedian follow-up 35.2 monthsYau 2025	median 23.7 months (18.8–29.4); 49% at 2 y (44–55%); 38% at 3 y (32–43%)	median 20.6 months (17.5–22.5); 39% at 2 y (34–45%); 24% at 3 y (19–30%)	HR 0.79 (95% CI 0.65–0.96)P=0.018 (two-sided stratified log-rank)Hazard ratio 0.79 (0.65 to 0.96) as given in the Lancet abstract, which does not state the confidence level of the interval; the FDA labeling (revised 4/2025, Table 79, same analysis: medians 23.7 vs 20.6 months, p 0.0180) gives it as a 95% CI. The overall survival curves crossed early: the abstract reports a hazard ratio of 1.65 (95% CI 1.12 to 2.43) for deaths in the first 6 months and 0.61 (0.48 to 0.77) thereafter.

Results reported for CheckMate 9DW
Endpoint	Analysis	Nivolumab plus ipilimumab	Lenvatinib or sorafenib	Effect
OSAll randomly assigned patients	interimmedian follow-up 35.2 monthsYau 2025	median 23.7 months (18.8–29.4); 49% at 2 y (44–55%); 38% at 3 y (32–43%)	median 20.6 months (17.5–22.5); 39% at 2 y (34–45%); 24% at 3 y (19–30%)	HR 0.79 (95% CI 0.65–0.96)P=0.018 (two-sided stratified log-rank)Hazard ratio 0.79 (0.65 to 0.96) as given in the Lancet abstract, which does not state the confidence level of the interval; the FDA labeling (revised 4/2025, Table 79, same analysis: medians 23.7 vs 20.6 months, p 0.0180) gives it as a 95% CI. The overall survival curves crossed early: the abstract reports a hazard ratio of 1.65 (95% CI 1.12 to 2.43) for deaths in the first 6 months and 0.61 (0.48 to 0.77) thereafter.

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
OS	0.79	0.65–0.96

Illustrative — modelled from reported values, not trial data. OS, interim.

Show curves

Nivolumab plus ipilimumab (experimental)
Lenvatinib or sorafenib (control)

Data table (modelled values)

Months	Nivolumab plus ipilimumab	Lenvatinib or sorafenib
0	100.0%	100.0%
10	77.3%	73.0%
19	57.7%	49.7%
29	43.4%	31.7%
39	38.0%	24.0%

Appears in

2025 CheckMate 9DW: first-line nivolumab plus ipilimumab

Sources

Yau T, Galle PR, Decaens T, Sangro B, Qin S, da Fonseca LG, 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;405(10492):1851-1864.
PubMed DOI