FDA Accepts Nivolumab/Ipilimumab Application for First-Line HCC Treatment

Microscopic, photorealistic image of liver cancer cells - Generated with Adobe FireflyMicroscopic, photorealistic image of liver cancer cells - Generated with Adobe Firefly

• The FDA has accepted the supplemental biologics license application (sBLA) for nivolumab (Opdivo) plus ipilimumab (Yervoy) in the first line for patients with unresectable hepatocellular carcinoma (HCC).
• A Prescription Drug User Fee Act (PDUFA) target action date of April 21, 2025, has been set.
• The sBLA is supported by data from the phase 3 CheckMate -9DW trial (NCT04039607).

The sBLA of nivolumab and ipilimumab for the first-line treatment of unresectable HCC has been accepted by the FDA, and a PDUFA target action date of April 21, 2025, has been set.¹

“HCC is the most common form of liver cancer and is often diagnosed when surgery is no longer an option. With the number of individuals diagnosed with HCC in the United States increasing over the last decade, new treatment options are urgently needed,” said Dana Walker, MD, MSCE, vice president, global program lead, gastrointestinal and genitourinary cancers, Bristol Myers Squibb, in a press release. “[Nivolumab] plus [ipilimumab] showed superior survival benefit compared [with] other available treatment options, and we look forward to working with the FDA to advance our application to potentially bring a new first-line treatment option to patients.”

The sBLA is supported by data from the phase 3 CheckMate -9DW study.First results were presented at the 2024 American Society of Clinical Oncology Annual Meeting. In the study, 668 patients were randomized 1:1 to receive nivolumab and ipilimumab or investigator’s choice of lenvatinib (Lenvima) or sorafenib (Nexavar).²

At a median follow-up of 35.2 months (range, 26.8-48.9), the median overall survival (OS) was 23.7 months in the combination arm vs 20.6 months with lenvatinib or sorafenib (HR, 0.79; 95% CI, 0.65-0.96; P =.0180). Respectively, the 24-month OS rates were 49% (range, 44%-55%) and 39% (range, 34%-45%). This OS benefit was statistically significant.

The overall response rate (ORR) in the combination arm was 36% (95% CI, 31%-41%) with a 7% complete response (CR) rate vs 13% (95% CI, 10%-17%) with a 2% CR rate in the lenvatinib/sorafenib arm. The median duration of response between arms was 30.4 months (95% CI, 21.2-not evaluable) and 12.9 months (95% CI, 10.2-31.2), respectively.

Regarding safety, treatment-related adverse events (TRAEs) were reported in 84% of the combination arm and 91% of the lenvatinib/sorafenib arm, and grade 3 or 4 TRAEs were 41% and 42%, respectively. Any-grade TRAEs led to treatment discontinuation in 18% of patients receiving nivolumab and ipilimumab and 10% receiving lenvatinib or sorafenib.

REFERENCES:

1. Bristol Myers Squibb receives U.S. Food and Drug Administration sBLA acceptance for first-line treatment of unresectable hepatocellular carcinoma. News release. Bristol Myers Squibb. August 21, 2024. Accessed August 21, 2024. https://tinyurl.com/tx6c47fe

2. 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;42:1 LBA4008-LBA4008(2024). doi:10.1200/JCO.2024.42.17_suppl.LBA4008