FDA Grants Full Approval to Opdivo Plus Yervoy Regimen for Unresectable or Metastatic Hepatocellular Carcinoma
Approval of Opdivo plus Yervoy combination was based on results from the Phase III CheckMate-9DW trial, which demonstrated significantly improved overall survival and overall response rate in patients with unresectable or metastatic hepatocellular carcinoma.
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The FDA has granted full approval to Bristol Myers Squibb’s (BMS) dual immunotherapy regimen of Opdivo (nivolumab) plus Yervoy (ipilimumab) for adults with unresectable or metastatic hepatocellular carcinoma (HCC). The regulatory action was based on improvements in overall survival (OS) and overall response rate (ORR) demonstrated in the Phase III CheckMate-9DW trial, evaluating the combination in comparison to standard tyrosine kinase inhibitor (TKI) monotherapy (lenvatinib or sorafenib).
In 2020, Opdivo plus Yervoy was granted accelerated approval for this indication based on results from the Phase I/II CheckMate-040 trial.1
“The CheckMate-9DW approval is an important advancement for patients, considering the incidence of liver cancer has tripled in the last four decades, yet prognosis for HCC patients remains poor,” said Aiwu Ruth He, MD, PhD, CheckMate-9DW study investigator at MedStar Georgetown University Hospital, in a press release. “The availability of a new first-line treatment option that demonstrated a deep response can offer adults with this form of liver cancer long-term overall survival and may help address an unmet need. Given the strength of evidence from the trial, especially considering the selection and performance of a strong comparator arm, I believe that Opdivo plus Yervoy has the potential to become a standard of care for the first-line treatment of patients with unresectable or metastatic HCC.”
The randomized, open-label CheckMate-9DW trial compared the combination of Opdivo plus Yervoy to investigator’s choice of lenvatinib or sorafenib. A total of 668 patients were randomly assigned to receive either Opdivo 1 mg/kg plus Yervoy 3 mg/kg every three weeks for up to four doses, followed by 480 mg of Opdivo monotherapy every four weeks, or single agent lenvatinib or sorafenib. The primary endpoint of the study was OS, while key secondary endpoints included ORR and time to symptom deterioration.
Results showed that the dual immunotherapy regimen improved median OS to 23.7 months, compared to 20.6 months with the TKIs. Additionally, the combination demonstrated an ORR of 36.1%, compared to 13.2% in the single-agent group. Further, Opdivo plus Yervoy had a median duration of response of 30.4 months versus 12.9 months with lenvatinib or sorafenib.
No new safety signals were observed with Opdivo plus Yervoy, however, serious adverse events (AEs) occurred in 53% of patients treated with the combination. The most common non-liver-related serious AEs were diarrhea/colitis, gastrointestinal hemorrhage, and rash. Liver-related serious AEs occurred in 17% of patients, and fatal AEs occurred in 3.6%. Treatment discontinuation due to an AE occurred in 27% of patients. The most common treatment-related AEs included rash, pruritus, fatigue, and diarrhea.1
Last week, BMS announced that the Opdivo plus Yervoy regimen received FDA approval as a first-line treatment for adult and pediatric patients aged 12 years and older with previously untreated, unresectable, or metastatic microsatellite instability-high or mismatch repair deficient colorectal cancer. This second indication was based on data from the Phase III CheckMate-8HW trial.2
“Bringing Opdivo plus Yervoy to patients with HCC in the first-line setting is a testament to our ongoing commitment to research and delivering important progress for people living with cancer,” said Wendy Short Bartie, SVP, oncology commercialization, BMS, in the press release. “Today’s approval builds on the legacy of our dual immunotherapy and the value it has brought to patients for years.1 We are thrilled to add this indication for this important therapy – our second approval for Opdivo plus Yervoy in the gastrointestinal space this week alone – and look forward to providing a new first-line treatment option to patients in need.”
References
1. U.S. Food and Drug Administration Approves Opdivo® (nivolumab) plus Yervoy® (ipilimumab) as a First-Line Treatment for Unresectable or Metastatic Hepatocellular Carcinoma. BMS. April 11, 2025. Accessed April 14, 2025. https://news.bms.com/news/details/2025/U-S--Food-and-Drug-Administration-Approves-Opdivo-nivolumab-plus-Yervoy-ipilimumab-as-a-First-Line-Treatment-for-Unresectable-or-Metastatic-Hepatocellular-Carcinoma/default.aspx
2. FDA Approves Opdivo Plus Yervoy Regimen for MSI-H/dMMR Colorectal Cancer. PharmExec. April 9, 2025. Accessed April 14, 2025. https://www.pharmexec.com/view/fda-approves-opdivo-plus-yervoy-regimen-msi-h-dmmr-colorectal-cancer
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