Bristol Myers Squibb's Opdivo plus Yervoy Seeks FDA Approval as First-Line Therapy for Unresectable Hepatocellular Carcinoma
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On August 22, Bristol Myers Squibb announced that the U.S. Food and Drug Administration (FDA) had accepted its supplemental Biologics License Application (sBLA) for the combination therapy of its blockbuster PD-1 inhibitor Opdivo (nivolumab) and CTLA-4 targeted antibody Yervoy (ipilimumab), primarily for potential first-line treatment in adult patients with unresectable hepatocellular carcinoma (HCC).
Among them, Opdivo aims to help restore anti-tumor immune response by utilizing the body's own immune system to fight cancer. Yervoy targets and inhibits CTLA-4, and CTLA-4 antibodies enhance tumor-killing ability by boosting T-cell activity. Yervoy was approved by the U.S. FDA in 2011 for the treatment of advanced melanoma and is the world’s first approved CTLA-4 antibody drug. The combination therapy of Opdivo and Yervoy has previously been approved as a second-line treatment option for patients with advanced HCC.
The approval of this application is also based on the results of the Phase 3 CheckMate-9DW study. CheckMate-9DW is a Phase 3 randomized, open-label trial evaluating the efficacy and safety of Opdivo in combination with Yervoy versus investigator’s choice of sorafenib or lenvatinib monotherapy for the treatment of patients with advanced HCC who have not previously received systemic therapy. The trial enrolled approximately 668 patients, with overall survival as the primary endpoint and key secondary endpoints including objective response rate and time to symptom deterioration.
Results from the CheckMate-9DW Phase 3 trial were presented as an oral report at the 2024 ASCO Annual Meeting:
With a median follow-up of approximately 35.2 months, Opdivo plus Yervoy treatment demonstrated:
• The primary endpoint of overall survival (OS) demonstrated a statistically significant and clinically meaningful improvement. The median OS for the Opdivo plus Yervoy group was 23.7 months (95% CI: 18.8–29.4), compared to 20.6 months (95% CI: 17.5–22.5) for the lenvatinib or sorafenib group (HR: 0.79; p=0.018). The overall survival benefit was generally consistent across patient subgroups.
• The key secondary endpoint, objective response rate (ORR), demonstrated statistically significant and clinically meaningful improvement. The ORR was 36% (95% CI: 31-42) in the Opdivo plus Yervoy group, compared to 13% (95% CI: 10-17) in the lenvatinib or sorafenib group.
• The complete response rate (CR) of Opdivo combined with Yervoy was higher at 7%, compared to 2% in the lenvatinib or sorafenib groups. Responses were durable; the median duration of response for Opdivo combined with Yervoy was 30.4 months (95% CI: 21.2-NE) in patients who had a response, while it was 12.9 months (95% CI: 10.2-31.2) for lenvatinib or sorafenib.
• Compared with lenvatinib or sorafenib, the risk of symptom deterioration with Opdivo combined with Yervoy was significantly reduced by 24% (HR: 0.76, 95% CI: 0.62-0.93; p=0.0059).
The safety of the Opdivo and Yervoy combination is consistent with previously reported data and is manageable under the established regimen.
In addition, Bristol-Myers Squibb is actively exploring combination therapies based on Opdivo for advanced or metastatic gastric cancer (GC), gastroesophageal junction cancer (GEJC), and esophageal adenocarcinoma (EAC), as well as unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
Ian M. Waxman, Vice President of Bristol-Myers Squibb and Global Program Head of Oncology Development, stated, "Regimens based on Opdivo have demonstrated survival benefits and have transformed the outlook for patients with GC, GEJC, EAC, and ESCC."
References:
Bristol-Myers Squibb Official Website
https://news.bms.com/news/corporate-financial/2024/Bristol-Myers-Squibb-Announces-Opdivo-nivolumab-Plus-Yervoy-ipilimumab-Significantly-Improved-Overall-Survival-Compared-to-Lenvatinib-or-Sorafenib-as-First-Line-Treatment-for-Patients-with-Advanced-Hepatocellular-Carcinoma-in-CheckMate--9DW-Trial/default.aspx
