The Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) for a single priming dose of tremelimumab added to durvalumab for the treatment of patients with unresectable hepatocellular carcinoma (HCC).
Tremelimumab is a human monoclonal antibody that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). The STRIDE regimen (Single Tremelimumab Regular Interval Durvalumab) was evaluated as a first-line treatment in the phase 3 HIMALAYA trial (ClinicalTrials.gov Identifier: NCT03298451).
Patients received a single priming dose of tremelimumab 300mg added to durvalumab 1500mg (n=393) followed by durvalumab (n=389) every 4 weeks vs sorafenib (n=389). The primary endpoint was overall survival.
Results showed that patients treated with the STRIDE regimen experienced a 22% reduction in the risk of death vs sorafenib (hazard ratio [HR], 0.78, 96.02% CI 0.65-0.93; P =.0035). Median overall survival was reported to be 16.4 months for the STRIDE group compared with 13.8 months for the sorafenib group.
Objective response rate and median duration of response, respectively, were 20.1% and 22.3 months for STRIDE and 5.1% and 18.4 months for sorafenib. Durvalumab monotherapy also demonstrated noninferior overall survival to sorafenib (HR, 0.86; 95.67% CI 0.73-1.03).
Nearly 31% of STRIDE-treated patients were still alive at 3 years vs 20% of those who received sorafenib. No new safety signals were identified during the trial.
“Patients with advanced liver cancer are in great need of new treatment options, and we are working closely with the FDA to bring this novel approach to patients in the US as soon as possible,” said Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca.
The FDA’s decision on the application is expected during the fourth quarter of 2022. The combination was previously granted Orphan Drug designation for the treatment of HCC. Additionally, a supplemental BLA has been submitted for durvalumab (Imfinzi) for this indication.
References
Tremelimumab accepted under Priority Review in the US for patients with unresectable liver cancer in combination with Imfinzi. News release. April 25, 2022. https://www.astrazeneca.com/media-centre/press-releases/2022/tremelimumab-us-priority-review-imfinzi-combo.htmlImfinzi plus tremelimumab demonstrated unprecedented survival in 1st-line unresectable liver cancer with 31% of patients alive at three years. News release. January 18, 2022. https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2022/imfinzi-plus-tremelimumab-unprecedented-survival-1st-line-unresectable-liver-cancer.html
