Tremelimumab-durvalumab regimen extends OS in unresectable HCC
The addition of tremelimumab to first-line durvalumab significantly improved OS compared with sorafenib for certain patients with unresectable hepatocellular carcinoma, according to topline data released by the agent’s manufacturer.
The combination also exhibited a favorable safety profile, results of the randomized phase 3 HIMALAYA trial showed.
Tremelimumab (MedImmune/AstraZeneca) is an anti-CTLA-4 monoclonal antibody. Durvalumab (Imfinzi, AstraZeneca), a human monoclonal antibody that binds to PD-L1, is approved in the United States for treatment of certain patients with lung cancer.
The open-label, multicenter HIMALAYA trial included 1,324 patients with unresectable HCC who had not received prior systemic therapy and were ineligible for localized treatment.
Researchers assigned patients to one of three treatment regimens: durvalumab monotherapy; the STRIDE regimen, which includes a single 300-mg priming dose of tremelimumab with 1,500 mg durvalumab followed by durvalumab every 4 weeks; or standard-of-care sorafenib (Nexavar, Bayer), a multi-kinase inhibitor.
The study met its primary endpoint, showing a statistically significant OS improvement with the STRIDE regimen compared with sorafenib. The addition of tremelimumab to durvalumab did not increase severe hepatic toxicity.
The study also met a key secondary endpoint, showing OS noninferiority with durvalumab monotherapy vs. sorafenib. Durvalumab also appeared more tolerable than sorafenib.
“HIMALAYA is the first phase 3 trial to add a novel single priming dose of an anti-CTLA4 antibody to another checkpoint inhibitor,” principal investigator Ghassan Abou-Alfa, MD, MBA, attending physician at Memorial Sloan Kettering Cancer Center, said in an AstraZeneca-issued press release. “This serves to boost the patient’s own immune system against their liver cancer, aiming to maximize long-term survival with minimal side effects. This is very exciting news for our patients.”
Complete results from the HIMALAYA trial will be submitted for presentation at a medical meeting.