FDA Accepts Bristol Myers Squibb Application for Unresectable Hepatocellular Carcinoma First-Line Treatment

Two Bristol Myers Squibb products, Opdivo (nivolumab) plus Yervoy (ipilimumab), have been accepted in tandem with one another as a potential first-line treatment for adult patients with unresectable hepatocellular carcinoma (HCC). A press release from Bristol Myers Squibb on Aug. 21, 2024 said that FDA had accepted the company’s supplemental Biologics License Application based on results from a Phase III trial (CheckMate -9DW), and set a Prescription Drug User Fee Act goal date of Apr. 21, 2025 (1).

Most cases of HCC are caused by hepatitis B or C infections, although Bristol Myers Squibb said metabolic syndrome and nonalcoholic steatohepatitis are on the rise as additional causes and may contribute to increased HCC rates. Right now, HCC accounts for anywhere from 75–85% of all liver cancers, with liver cancer being the third-most frequent cause of cancer death worldwide (1). HCC is most commonly diagnosed at an already advanced stage, and up to 70% of patients—especially those considered high-risk after surgery or ablation—experience a recurrence within five years.

“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,” Dana Walker, MD, vice president and global program lead for gastrointestinal and genitourinary cancers at Bristol Myers Squibb, said in the press release. “Opdivo plus Yervoy showed superior survival benefit compared to other available treatment options, and we look forward to working with FDA to advance our application to potentially bring a new first-line treatment option to patients.”

In the Phase III trial, results of which were shared on June 4, 2024 at the 2024 American Society of Oncology Annual Meeting in Chicago, Ill., the median primary endpoint of overall survival was 23.7 months following a regimen of Opdivo plus Yervoy, compared to 20.6 months with lenvatinib or sorafenib (2). The key secondary endpoint of objective response rate was 36% versus 13% considering these two treatment approaches, and complete response rate was higher (7% versus 2%) with more durable responses (median duration of 30.4 months versus 12.9).

“Despite recent advances in the treatment of HCC, prognosis remains poor for patients with advanced HCC, and therapies that improve survival and help delay disease progression are needed,” Peter R. Galle, MD, of the University Medical Center in Mainz, Germany said at the time. “These data from CheckMate -9DW confirm the efficacy of the combination of nivolumab and ipilimumab and ability to extend survival, which is very encouraging.”

References

1. Bristol Myers Squibb. Bristol Myers Squibb Receives US Food and Drug Administration sBLA Acceptance for First-Line Treatment of Unresectable Hepatocellular Carcinoma. Press Release. Aug. 21, 2024.
2. Bristol Myers Squibb. 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. Press Release. June 4, 2024.