Frontline Nivolumab Plus Ipilimumab for Patients With Unresectable Hepatocellular Carcinoma
Results From the CheckMate 9DW Trial
Results From the CheckMate 9DW Trial
Ruth He, MD, PhD, Columbia University, New York, New York, discusses results from the CheckMate 9DW trial, evaluating nivolumab plus ipilimumab in the first-line setting for patients with unresectable hepatocellular carcinoma (HCC). Based on the results from this trial, on April 11, 2025, the US Food and Drug Administration approved the use of nivolumab plus ipilimumab for this patient population.
Dr He concluded, “The approval of nivolumab plus ipilimumab in unresectable HCC now sets a new landmark for the treatment landscape of unresectable HCC.”
Transcript:
Hi, this is Dr Ruth He. I'm a GI medical oncologist and investigator from Columbia University and I'm here to talk about the recent approval of nivolumab plus ipilimumab in advanced HCC and unresectable HCC. This is based on the positive global, phase 3 study CheckMate 9DW.
This study enrolled patients with unresectable HCC. Patients were randomized 1-to-1 to the combination of nivolumab plus ipilimumab versus the choice of a TKI. In this study, 85% of patients in the control arm received [lenvatinib]. This is the first positive global study using lenvatinib as a comparative arm, and met its primary endpoint. Patients who received the combination of nivolumab-ipilimumab, after 3 years of follow up, achieved a median over survival of 23.7 months, and with a response rate of 36%. The duration of response was over 30 months.
This approval has provided another very effective treatment option and frontline therapy option for patients with unresectable HCC. This is a confirmatory study and the combination of nivolumab-ipilimumab was FDA-approved as a second-line therapy in 2020. And now, based on this confirmatory, global, phase 3 study, the combination now has a first-line indication. It will be a good option for patients with unresectable HCC.
In terms of safety, there's reported immune-mediated adverse events, but the adverse event profile is very consistent with previous data on other trials and there were no new safety concerns.
What should clinicians keep in mind about this combination?
When we give patients treatment with immune checkpoint inhibitors, we always need to keep immune-mediated adverse events as a differential diagnosis when a patient comes in with medical issues. Even patients that have received immune checkpoint inhibitors in the past, we always need keep that as a differential diagnosis and try to recognize the early signs of immune-mediated adverse events and address those symptoms early on with treatment to ensure a good outcome in patients.
What are the next steps for this research?
The approval of nivolumab plus ipilimumab in unresectable HCC now sets a new landmark for the treatment landscape of unresectable HCC. I think we are always looking for better treatment with a good safety profile. Currently, there are a couple of trials testing triplet or combinations of immune checkpoint inhibitors with bispecific antibodies. I think down the line, in the future, we hope to see with the novel combinations that will even bring the response rate to a higher level and continue to improve patients’ outcomes in terms of the median overall survival.
There are other exciting studies ongoing, such as antibody-drug conjugates and cellular therapy, even for advanced stage HCC. I think we hope in the next few years that there's even more improved treatment for patients with HCC.
Source:
Galle PR, Decaens T, Kudo M, et al. Nivolumab (NIVO) plus ipilimumab (IPI) vs lenvatinib (LEN) or sorafenib (SOR) as first-line treatment for unresectable hepatocellular carcinoma (uHCC): First results from CheckMate 9DW. J Clin Oncol. 2024;42(17_suppl). doi:10.1200/JCOP.2024.42.17_suppl.LBA4008
