There was statistically significant and clinically meaningful overall survival benefit vs sorafenib as a first-line treatment for patients with unresectable hepatocellular carcinoma (HCC) in top-line results from a phase 3 trial.
AstraZeneca Friday released positive early results from the HIMALAYA phase 3 trial, showing that adding the biologic tremelimumab added to durvalumab (Imfinzi) demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit vs sorafenib as a first-line treatment for patients with unresectable hepatocellular carcinoma (HCC).
Patients had not received prior systemic therapy and were not eligible for localized treatment.
Data from the trial will be presented at a future medical meeting, the company said.
The dose and schedule of tremelimumab, an anti-CTLA4 antibody, and durvalumab is called the STRIDE regimen (Single Tremelimumab Regular Interval Durvalumab). The combination demonstrated a favorable safety profile, and the addition of tremelimumab to durvalumab did not increase severe hepatic toxicity.
By itself, durvalumab was noninferior in terms of OS to sorafenib with a numerical trend in favor of durvalumab and an improved tolerability profile compared with sorafenib.
The drugs were granted orphan drug designations by the FDA for the treatment of HCC in 2020. Tremelimumab was also granted orphan designation in the EU in HCC in 2020.
“HIMALAYA is the first Phase III trial to add a novel single priming dose of an anti-CTLA4 antibody to another checkpoint inhibitor, durvalumab. This serves to boost the patient’s own immune system against their liver cancer, aiming to maximize long-term survival with minimal side effects,” Ghassan Abou-Alfa, MD, MBA, attending physician at Memorial Sloan Kettering Cancer Center and principal investigator in the HIMALAYA Phase III trial, said in a statement.
Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca, said, “Inhibition of CTLA-4 has shown the ability to drive benefit particularly in the tail of the survival curve in several settings. This is the first time a dual immunotherapy regimen has improved overall survival as a [first]-line treatment for patients with unresectable liver cancer for whom treatment options are limited and long-term outcomes are poor.”
HIMALAYA was a randomized, open-label, multicenter, global phase 3 trial of durvalumab monotherapy and the STRIDE regimen, comprising a single priming dose of tremelimumab 300 mg added to durvalumab 1500 mg followed by durvalumab every 4 weeks vs sorafenib in a total of 1324 patients with unresectable, advanced HCC.
The trial was conducted in 190 centers across 16 countries, including in the United States, Canada, Europe, South America, and Asia.
Adverse events include immune-mediated adverse effects, which may be severe; the most common ones are pneumonitis, colitis, hepatitis, and endocrinopathies.
Liver cancer, of which HCC is the most common type, is the sixth leading cause of cancer death in the United States. Only about 3% of patients with advanced disease survive 5 years.