FDA Grants Priority Review to Enhertu for HER2-Positive Metastatic Solid Tumors
核心洞察
The FDA granted Priority Review to Enhertu for HER2 (搜索)-positive unresectable or metastatic solid tumors with no satisfactory alternative options.
The sBLA is based on the DESTINY-PanTumor02 Phase II trial, which showed clinically meaningful responses and survival benefits in previously treated patients.
Enhertu could become the first HER2 (搜索)-directed therapy and antibody-drug conjugate with a tumor-agnostic indication if approved.
AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab deruxtecan) has received Priority Review from the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with unresectable or metastatic HER2 (搜索)-positive (immunohistochemistry [IHC] 3+) solid tumors who have received prior treatment or have no satisfactory alternative treatment options. This action accelerates the potential availability of a new treatment option for patients with various HER2-expressing cancers.
The supplemental Biologics License Application (sBLA) is supported by data from the ongoing DESTINY-PanTumor02 Phase II trial, which demonstrated clinically meaningful and durable responses, leading to a clinically meaningful survival benefit in previously treated patients across HER2 (搜索)-expressing metastatic solid tumors, including biliary tract, bladder, cervical, endometrial, ovarian cancers, and other tumors. Data from other trials, including DESTINY-Lung01 and DESTINY-CRC02, were also included in the submission.
Clinical Efficacy in HER2-Expressing Tumors
The DESTINY-PanTumor02 trial is a global, multicenter, multi-cohort, open-label Phase II trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) for the treatment of previously treated HER2 (搜索)-expressing tumors, including biliary tract cancer (搜索), bladder cancer (搜索), cervical cancer (搜索), endometrial cancer (搜索), ovarian cancer (搜索), pancreatic cancer (搜索), or other tumors. The primary efficacy endpoint is confirmed objective response rate (ORR) as assessed by investigator.
Results from DESTINY-PanTumor02 were presented at the 2023 European Society for Medical Oncology Congress and simultaneously published in the Journal of Clinical Oncology. The safety profile observed across the trials was consistent with previous clinical trials of Enhertu, with no new safety concerns identified.
Priority Review and Breakthrough Therapy Designation
The FDA grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions, or enhancing patient compliance. The Prescription Drug User Fee Act (PDUFA) date, the FDA action date for their regulatory decision, is during the second quarter of 2024.
This Priority Review follows the receipt of Breakthrough Therapy Designation (BTD) in the US in August 2023 for Enhertu in metastatic HER2-positive solid tumors (搜索).
HER2 as a Target in Solid Tumors
HER2 (搜索) is a tyrosine kinase receptor growth-promoting protein expressed on the surface of various tissue cells throughout the body and is involved in normal cell growth. In some cancers, HER2 expression is amplified, or the cells have activating mutations. HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis.
While HER2 (搜索)-directed therapies have been used to treat breast, gastric, lung, and colorectal cancers, more research is needed to evaluate their potential role in treating other HER2-expressing solid tumor types. In these solid tumors, HER2-positive expression, classified as IHC 3+, has been observed at rates from 1% to 28%. There is an unmet need for effective therapies for certain HER2-expressing solid tumors, particularly for those who have progressed on or are refractory to standard of care therapies, as there are currently no approved HER2-directed therapies for these cancers.
Ongoing Clinical Development
A comprehensive clinical development program is underway globally, evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2 (搜索)-targetable cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, stated, "Today’s Priority Review for the first tumor-agnostic submission for Enhertu reflects the potential of this medicine to redefine the treatment of HER2 (搜索)-expressing cancers."
Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, added, "If approved, Enhertu could become the first HER2 (搜索)-directed therapy and antibody drug conjugate with a tumor-agnostic indication, providing patients with a potential new treatment option."