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The FDA has approved the CTLA-4 immune checkpoint inhibitor tremelimumab (Imjudo) as part of a first-line immunotherapy combination for unresectable hepatocellular cancer (HCC), on Monday.

Under the specifics of the new indication, tremelimumab is given as a single 300 mg priming dose along with the PD-L1 inhibitor durvalumab (Imfinzi) at a dose of 1,500 mg every 4 weeks -- dubbed the STRIDE regimen (single tremelimumab, regular interval durvalumab).

Tremelimumab becomes only the second anti-CTLA-4 drug to garner an approval from the agency, following the 2011 approval of ipilimumab (Yervoy).

Data supporting tremelimumab-durvalumab's approval came from the , an international, open-label trial that randomized more than 1,300 patients with advanced, unresectable HCC who had not yet been treated with systemic therapy.

Overall survival (OS) improved from a median 13.8 months with single-agent sorafenib (Nexavar) to 16.4 months with the dual immunotherapy, representing a 22% reduction in the risk for death during the study period (HR 0.78, 95% CI 0.66-0.92, P=0.0035). At 3 years, OS rates were an estimated 31% with tremelimumab-durvalumab versus 20% with sorafenib.

"Patients with unresectable liver cancer are in need of well-tolerated treatments that can meaningfully extend overall survival," said HIMALAYA principal investigator Ghassan Abou-Alfa, MD, of Memorial Sloan Kettering Cancer Center in New York City, in a statement. "Safety data showed no increase in severe liver toxicity or bleeding risk for the combination, important factors for patients with liver cancer who also have advanced liver disease."

According to trial data presented at the Gastrointestinal Cancers Symposium earlier this year, median progression-free survival was similar for patients receiving tremelimumab-durvalumab or sorafenib (3.78 vs 4.07 months, respectively), while response rates favored the combination (20.1% vs 5.1%).

Grade 3/4 adverse events (AEs) occurred at a similar frequency (50.5% with the combination and 52.4% with sorafenib), though serious treatment-related AEs were less frequent (25.8% and 36.9%, respectively).

In its approval announcement, AstraZeneca warned of the risks for embryo-fetal toxicity with tremelimumab-durvalumab; for severe and fatal immune-mediated adverse events (skin reactions, pneumonitis, colitis, nephritis, hepatitis, pancreatitis); and for immune-mediated endocrinopathies such as type 1 diabetes, thyroid disorders, hypophysitis, and adrenal insufficiency.

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