Dr Harding on the FDA Approval of Nivolumab Plus Ipilimumab for Unresectable or Metastatic HCC

"What was important about this study [was that], after approximately 1 year, we saw a separation of the curves; at 24 and 36 months, [respectively], we saw 49% and 38% of patients alive [in the ipilimumab-plus-nivolumab arm]. This [regimen] shows operating characteristics that are very similar to other CTLA-4–based combinations in this disease."

James J. Harding, MD, an associate attending physician at Memorial Sloan Kettering Cancer Center, shared key efficacy data from the phase 3 CheckMate 9DW trial (NCT04039607) that supported the FDA’s April 2025 decision to grant full approval to nivolumab (Opdivo) plus ipilimumab (Yervoy) for the first-line treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC).

Data from the CheckMate 9DW trial demonstrated a statistically significant overall survival (OS) benefit with the dual checkpoint inhibitor regimen compared with control therapy consisting of investigator’s choice of sorafenib (Nexavar) or lenvatinib (Lenvima), Harding began. At a median follow-up of 35.2 months (range, 26.8-48.9), patients treated with nivolumab plus ipilimumab (n = 335) achieved a median OS of 23.7 months (95% CI, 18.8-29.4), compared with 20.6 months (95% CI, 17.5-22.5) for those who received control therapy (n = 333; HR, 0.79; 95% CI, 0.65-0.96; P < .018), Harding explained. The Kaplan-Meier curves for OS began to separate at approximately 12 months, and by 24 and 36 months, 49% (95% CI, 44%-55%) and 38% (95% CI, 32%-43%) of patients in the immunotherapy arm, respectively, remained alive, he reported. This finding highlights the durable clinical benefit associated with CTLA-4–based combinations in this disease, Harding said.

Although no significant difference in median progression-free survival (PFS) was observed, this finding is consistent with known characteristics of immune checkpoint inhibitors, which often do not affect early disease progression but can confer long-term survival benefits, Harding continued. Importantly, the confirmed objective response rate (ORR) with nivolumab plus ipilimumab was 36.1% (95% CI, 31.0%-41.5%), with complete responses (CRs) and partial responses (PRs) in 7% and 29% of patients, respectively, Harding stated. This was superior to the 13.2% ORR (95% CI, 9.8%-17.3%) observed in the control arm, which included respective CR and PR rates of 2% and 11%, Harding added. Overall, these results support the use of nivolumab plus ipilimumab as a frontline standard of care for patients with advanced HCC, particularly those likely to benefit from immune-based strategies capable of producing sustained clinical responses, Harding concluded.