The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending the approval of Opdivo (nivolumab) in combination with Yervoy (ipilimumab) for two distinct cancer indications. These include the first-line treatment of adult patients with unresectable or advanced hepatocellular carcinoma (HCC) and those with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) unresectable or metastatic colorectal cancer (CRC). These recommendations are based on the results from the Phase 3 CheckMate -9DW and CheckMate -8HW trials, respectively.
CheckMate -9DW: Advanced Hepatocellular Carcinoma
The CHMP's recommendation for HCC is based on the Phase 3 CheckMate -9DW trial. The results, presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in June 2024, demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS), the trial's primary endpoint. The median OS was 23.7 months for the Opdivo plus Yervoy combination compared to 20.6 months for patients treated with investigator's choice of lenvatinib or sorafenib. The safety profile of the combination remained consistent with previously reported data, with no new safety signals detected.
HCC accounts for approximately 90% of all liver cancer cases globally. When diagnosed at an advanced stage, effective treatment options are limited, resulting in sub-optimal prognosis and overall survival.
Dana Walker, M.D., M.S.C.E., vice president, Opdivo global program lead, Bristol Myers Squibb, stated, "The positive opinion received by the CHMP is a significant step forward in providing patients with additional treatment options, and we look forward to the upcoming European Commission review and the potential to expand the treatment landscape for adult patients with unresectable or advanced hepatocellular carcinoma."
CheckMate -8HW: MSI-H/dMMR Colorectal Cancer
The CHMP also recommended Opdivo plus Yervoy for the first-line treatment of adult patients with MSI-H or dMMR unresectable or metastatic CRC. Data from the CheckMate -8HW trial showed a 79% reduction in the risk of disease progression or death compared to chemotherapy in this patient population.
Next Steps
The CHMP opinions will now be reviewed by the European Commission (EC), which holds the authority to approve medicines for use in the European Union. A final decision from the EC is anticipated in the coming months. The U.S. Food and Drug Administration (FDA) has also accepted Bristol Myers Squibb's supplemental Biologics License Application (sBLA) for Opdivo plus Yervoy as a potential first-line treatment option for adult patients with unresectable HCC, with a Prescription Drug User Fee Act (PDUFA) goal date of April 21, 2025. Opdivo plus Yervoy was granted accelerated approval by the U.S. FDA in 2020 based on results from the Phase 2 CheckMate -040 trial and has been an established second-line treatment for patients with advanced HCC.
