Dr He on the FDA Approval of Nivolumab Plus Ipilimumab for Unresectable/Metastatic HCC

“The median OS [with nivolumab plus ipilimumab] was 23.7 months—the longest so far for advanced HCC. I found that to be very exciting [as it] sort of creates a new landmark for this disease.”

Aiwu Ruth He, MD, PhD, a gastrointestinal medical oncologist at the MedStar Health Lombardi Cancer Center, discussed key findings from the pivotal phase 3 CheckMate 9DW trial (NCT04039607), which supported the FDA approval of nivolumab (Opdivo) plus ipilimumab (Yervoy) for the first-line treatment of patients with unresectable or metastatic hepatocellular carcinoma (HCC) on April 11, 2025.

In the trial, the combination of nivolumab and ipilimumab generated a median overall survival (OS) of 23.7 months (95% CI, 18.8-29.4), representing the longest reported overall survival (OS) in this disease setting to date and marking a significant advancement in treatment outcomes compared with standard-of-care therapies, He began. In the lenvatinib (Lenvima)/sorafenib (Nexavar) comparator arm, the median OS was 20.6 months (95% CI, 17.5-22.5; HR, 0.79 [95% CI, 0.65-0.96; P < .018]). The objective response rate was 36.1% (95% CI, 31.0%-41.5%) with the combination. Notably, this is consistent with data previously observed in the phase 1/2 CheckMate 040 trial (NCT01658878), which investigated this combination in patients with advanced HCC who had previously received sorafenib, He said. This finding is notable, as phase 3 studies often fail to replicate the response rates and survival benefits seen in earlier phase 1 or 2 studies, He emphasized. However, the global CheckMate 9DW trial, which included a large and diverse patient population, sustained the efficacy signals observed with nivolumab plus ipilimumab in early-phase trials for first-line HCC, she stated.

Additional findings from the combination arm of CheckMate 9DW include a rapid median time to response of 2.2 months (range, 1.1-11.6) and a median duration of response of 30.4 months (95% CI, 21.2-not evaluable), indicating that patients who respond to this therapy tend to experience durable outcomes, He concluded.