CheckMate 9DW Expanded Analyses: Ipi/Nivo Versus Len/Sor for Unresectable HCC

Additional analyses from the CheckMate 9DW study shed further light on the clinical efficacy and safety of first-line ipilimumab plus nivolumab (ipi/nivo) for unresectable hepatocellular carcinoma (uHCC).

The latest data—which highlight efficacy by best overall response (BOR) subgroups, baseline characteristics, and additional safety analyses—were presented by Dr. Masatoshi Kudo and colleagues at the 2025 American Society of Clinical Oncology Gastrointestinal Cancers Symposium.

In the phase III CheckMate 9DW study, a total of 668 patients with previously untreated uHCC who were not eligible for curative surgical or locoregional therapies and had a Child-Pugh score of 5 or 6 and an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 were randomized to receive nivo (1 mg/kg) plus ipi (3 mg/kg every 3 weeks for up to 4 cycles), then nivo (480 mg every 4 weeks) or len (8 mg or 12 mg once daily) or sor (400 mg twice daily) until disease progression or unacceptable toxicity occurred. Nivo was given for a maximum of 2 years.

The primary endpoint of the study was overall survival (OS), and secondary endpoints included objective response rate (ORR) and duration of response (DOR).

Previous readouts of the study showed that first-line ipi/nivo provided improved OS benefit compared with lenvatinib plus sorafenib (len/sor), as well as a higher ORR with durable responses and a manageable safety profile in patients with uHCC.

Among the total patient population, 335 received ipi/nivo and 333 received len/sor. At a median follow-up of 35.2 months, the median OS was 23.7 months (95% CI, 18.8-29.4) and 20.6 months (95% CI, 17.5-22.5), respectively (hazard ratio [HR], 0.79; P=.018). Researchers also noted that the ORR was significantly higher with ipi/nivo than with len/sor (36% vs 13%; P<.0001). Median DOR was 30.4 months versus 12.9 months, respectively.

A survival benefit with ipi/nivo was observed across BOR subgroups at the 24-week landmark timepoint. Subgroup analyses showed ORR was higher with ipi/nivo across HCC etiologies and in patients with Barcelona Clinic Liver Cancer stage ≤B or C.

“These additional analyses from CheckMate 9DW demonstrate the efficacy and manageable safety of 1L [first-line] NIVO + IPI in uHCC and further support its use as a potential standard-of-care treatment option in this setting,” study authors concluded.