Trastuzumab Deruxtecan Granted FDA Priority Review for HER2-Positive Metastatic Breast Cancer

The FDA has announced the acceptance of a supplemental Biologics License Application (sBLA) for trastuzumab deruxtecan (Enhertu, AstraZeneca) for the treatment of adult patients with unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer who have received a prior anti-HER2-based regimen.

Trastuzumab deruxtecan is a HER2-directed antibody drug conjugate being developed by both AstraZeneca and Daiichi Sankyo.

The sBLA is being reviewed under the Real-Time Oncology Review (RTOR) program and Project Orbis, which are 2 initiatives of the FDA that are designed to bring effective cancer treatments to patients as early as possible. Additionally, RTOR allows the FDA to review components of an application before submission of the complete application.

“This review across geographies and the Priority Review in the US as part of Project Orbis is so important because it speaks to the transformative potential of Enhertu based on the unprecedented progression-free survival benefit in this setting,” said Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, in a press release. “The news reinforces the importance of bringing this potential new option to patients as quickly as possible.”

The recent sBLA is based on data from the DESTINY-Breast03 trial that were presented at the European Society for Medical Oncology Congress 2021. The trial demonstrated a 72% reduction in the risk of disease progression or death compared to T-DM1 in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane, according to the press release.

Further, DESTINY-Breast03 found that approximately all patients treated with trastuzumab deruxtecan during the trial were alive at 1 year (94.1%) compared to 85.9% of patients who were treated with T-DM1. The safety profile of trastuzumab deruxtecan was consistent with previous clinical trials, showing no new safety concerns identified and no grade 4 or 5 treatment-related interstitial lung disease events.

Trastuzumab deruxtecan is currently approved for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received 2 or more prior anti-HER2-based regimens in more than 30 countries based on the results from the DESTINY-Breast01 trial. It is being assessed further in a comprehensive clinical development program evaluating efficacy and safety across multiple HER2-targetable cancers, including breast, gastric, lung, and colorectal cancers.

REFERENCE

Enhertu granted Priority Review in the US for patients with HER2-positive metastatic breast cancer treated with a prior anti-HER2-based regimen. AstraZeneca. January 17, 2022. Accessed January 17, 2022. https://www.astrazeneca.com/media-centre/press-releases/2022/enhertu-granted-priority-review-for-breast-cancer.html