Daiichi Sankyo and AstraZeneca’s ENHERTU (fam-trastuzumab deruxtecan-nxki) has been granted Breakthrough Therapy Designation (BTD) in the U.S. for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-negative) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy. Patients with hormone receptor (HR) positive breast cancer should additionally have received or be ineligible for endocrine therapy.
ENHERTU is a specifically engineered HER2 directed antibody drug conjugate (ADC) being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca.
The U.S. Food and Drug Administration (FDA) BTD is designed to accelerate the development and regulatory review of potential new medicines that are intended to treat a serious condition and address a significant unmet medical need. The new medicine needs to have shown encouraging preliminary clinical results that demonstrate substantial improvement on a clinically significant endpoint over available medicines.
The FDA granted the BTD based on data from the pivotal DESTINY-Breast04 phase 3 trial where ENHERTU demonstrated a statistically significant and clinically meaningful improvement in both progression-free survival (PFS) and overall survival (OS) in patients with HER2 low unresectable and/or metastatic breast cancer with HR positive or HR negative disease versus physician’s choice of chemotherapy, which is the current standard of care. The positive topline results of DESTINY-Breast04 were recently announced and these data will be presented at an upcoming medical meeting.
The safety profile of ENHERTU was consistent with previous clinical trials with no new safety concerns identified. Overall interstitial lung disease (ILD) rates were consistent with that observed in late-line HER2 positive breast cancer trials of ENHERTU with a lower rate of grade 5 ILD observed, as determined by an independent adjudication committee.
“Historically, only patients with HER2 positive metastatic breast cancer were shown to benefit from HER2 directed therapy. DESTINY-Breast04, in which ENHERTU showed a clinically meaningful survival benefit in patients with HER2 low metastatic breast cancer, is the first trial to demonstrate that selecting patients for treatment based on low expression of HER2 has the potential to change the diagnostic and treatment paradigms for these patients,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “This Breakthrough Therapy Designation acknowledges the potential of ENHERTU to fulfill an unmet medical need and we look forward to working closely with the FDA to bring the first HER2 directed therapy to patients with metastatic breast cancer whose tumors have lower levels of HER2 expression.”
“Today’s news is a significant validation of the potential we see for the historic DESTINY-Breast04 trial to enable a paradigm shift in how breast cancer is classified by targeting the full spectrum of HER2 expression,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D, AstraZeneca. “ENHERTU continues to show transformative potential, and this milestone represents an important advance for patients with HER2 low metastatic breast cancer who are in urgent need of new treatment options and better outcomes.”
This is the third BTD for ENHERTU in breast cancer. ENHERTU previously received BTDs for the treatment of second-line HER2 positive metastatic breast cancer in 2021 and later-line HER2 positive metastatic breast cancer in 2017. Two additional BTDs for ENHERTU also have been granted in 2020 for HER2 mutant metastatic non-small cell lung cancer (NSCLC) and HER2 positive metastatic gastric cancer.