FDA Accepts BLA for Tremelimumab With Durvalumab for Priority Review

The FDA has accepted the biologic license application (BLA) of tremelimumab (AstraZeneca) for priority review, supporting the indication of a single priming dose of the anti-CTLA4 antibody added to durvalumab (Imfinzi; Astra Zeneca) for the treatment of individuals with unresectable hepatocellular carcinoma (HCC).

The novel dose and schedule of the combination is called the Single Tremelimumab Regular Interval Durvalumab (STRIDE) regimen.

A supplemental BLA has also been submitted for durvalumab in this indication.

“The HIMALAYA phase 3 trial showed an unprecedented 3-year overall survival in this setting with a single priming dose of tremelimumab added to durvalumab, highlighting the potential for this regimen to improve longer-term survival outcomes. 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 United States as soon as possible,” Susan Galbraith, executive vice president of oncology research and development at AstraZeneca, said in a statement.

The BLA for tremelimumab and supplemental BLA for durvalumab are based on the results from the HIMALAYA phase 3 trial that were presented at the 2022 American Society of Clinical Oncology Gastrointestinal Cancer Symposium.

In the trial, individuals who were treated with the STRIDE regimen experienced a 22% reduction in the risk of death compared with sorafenib. Additionally, nearly 31% of individuals were still alive 3 years later compared with 20% who took sorafenib.

The HYMALAYA trial aimed to study both durvalumab as a monotherapy and the STRIDE regimen, which comprised of a single priming dose of tremelimumab 300 mg added to durvalumab 1500 mg, followed by durvalumab every 4 weeks compared to sorafenib, a standard-of-care multi-kinase inhibitor.

The primary endpoint included overall survival (OS) for STRIDE compared to sorafenib. The key secondary endpoint included OS for durvalumab compared to sorafenib, objective response rate and progression-free survival for STRIDE and durvalumab as a monotherapy.

The safety profile for both STRIDE and durvalumab were consistent with the known profiles for each medication, and no new safety signals were identified.

The trial included 1324 individuals with unresectable, advanced HCC who had not been treated with a prior systemic therapy and were not eligible for locoregional therapy, which is treatment localized to the liver and surrounding tissues.

The trail was conducted in 181 centers across 16 countries that included the United States, Canada, Europe, South America, and Asia.

In January 2020, tremelimumab and durvalumab were granted orphan drug designation in the United States for the treatment of HCC.

The prescription Drug User Fee Act date, which is the FDA action date for its regulatory decision, is during the fourth quarter of 2022, following the use of a priority review voucher.

As part of an extensive clinical development program in gastrointestinal cancers, AstraZeneca is further assessing durvalumab across multiple liver cancer settings, including locoregional HCC in the EMERALD-1 and EMERALD-3 studies and adjuvant HCC in the EMERALD-2 study.

Reference

Tremelimumab accepted under priority review in the US for patients with unresectable liver cancer in combination with Imfinzi. AstraZeneca. News release. April 25, 2022. Accessed April 25, 2022. https://www.astrazeneca.com/media-centre/press-releases/2022/tremelimumab-us-priority-review-imfinzi-combo.html