FDA Accepts Bristol Myers Squibb’s sBLA for Opdivo and Yervoy Combination for Hepatocellular Carcinoma

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The FDA has accepted Bristol Myers Squibb’s (BMS) supplemental Biologics License Application (sBLA) for an immunotherapy combination of Opdivo (nivolumab) and Yervoy (ipilimumab) as a first-line treatment for adult patients with unresectable hepatocellular carcinoma (HCC). According to BMS, acceptance of the sBLA was based on promising results from the Phase III CheckMate-9DW trial, which demonstrated that the combination significantly improved overall survival (OS) compared to Lenvima (lenvatinib) or Nexavar (sorafenib).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, VP, global program lead, gastrointestinal and genitourinary cancers, BMS, in a press release. “Opdivo plus Yervoy showed superior survival benefit compared to 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 randomized, open-label CheckMate 9DW trial evaluated compared Opdivo plus Yervoy to investigator’s choice of Lenvima or Nexavar monotherapy in patients with unresectable or advanced HCC who have not received prior systemic therapy. The trial included 668 patients who were randomly assigned to receive either Opdivo plus Yervoy (Opdivo 1mg/kg plus Yervoy 3 mg/kg Q3W for up to four doses, followed by Opdivo monotherapy 480 mg for a maximum duration of two years) infusion, or single agent Lenvima or Nexavar as oral capsules in the control arm. The primary endpoint of the trial was OS, while secondary endpoints included objective response rate (ORR) and time to symptom deterioration.¹

Opdivo plus Yervoy was found to significantly improve OS, with a median OS of 23.7 months compared to 20.6 months for Lenvima or Nexavar. Additionally, the ORR in the Opdivo plus Yervoy cohort was 36% compared to 13% in the Lenvima or Nexavar cohort. Further, the complete response rate for the combination treatment was 7% compared to 2% for Lenvima or Nexavar. Lastly, Opdivo plus Yervoy demonstrated a significantly reduced risk of symptom deterioration of 24% compared to Lenvima or Nexavar.

The safety profile of Opdivo plus Yervoy remained consistent with previous studies and was reported to be manageable. Treatment-related adverse events (TRAEs) were found in 84% of trial participants with Opdivo plus Yervoy and 91% in trial participants with Lenvima or Nexavar. TRAEs that were grade 3/4 occurred in 41% and 42% of patients, respectively.²

According to the company, liver cancer is the third most frequent cause of cancer death worldwide, with HCC being the most common type of primary liver cancer. It accounts for anywhere from 75% to 85% of all liver cancers, and is commonly diagnosed in an advanced stage. Within five years, 70% of patients will experience recurrence, mainly those who are still considered to be at high risk after surgery or ablation.¹

“The combination of Opdivo plus Yervoy has been an established second-line treatment for patients with advanced HCC and, with these results, we can demonstrate that Opdivo plus Yervoy significantly increases survival and other key efficacy measures in the first-line setting for patients with advanced disease,” said Walker, in a press release. “We look forward to discussing these data with health authorities and potentially bringing the dual immunotherapy combination of Opdivo plus Yervoy to more patients.”

References

1. Bristol Myers Squibb Receives U.S. Food and Drug Administration sBLA Acceptance for First-Line Treatment of Unresectable Hepatocellular Carcinoma. BMS. August 21, 2024. Accessed August 21, 2024. https://news.bms.com/news/corporate-financial/2024/Bristol-Myers-Squibb-Receives-U.S.-Food-and-Drug-Administration-sBLA-Acceptance-for-First-Line-Treatment-of-Unresectable-Hepatocellular-Carcinoma/default.aspx

2. 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. BMS. June 4, 2024. Accessed August 21, 2024. 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