TOKYO and BASKING RIDGE, NJ – Daiichi Sankyo (TSE: 4568) and AstraZeneca’s (LSE/STO/Nasdaq: AZN) Biologics License Application (BLA) for datopotamab deruxtecan (Dato-DXd) has been accepted in the U.S. for the treatment of adult patients with unresectable or metastatic hormone receptor (HR) positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior systemic therapy for unresectable or metastatic disease.
Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed by Daiichi Sankyo and AstraZeneca.
The Prescription Drug User Fee Act (PDUFA) date, the U.S. Food and Drug Administration (FDA) action date for its regulatory decision, is January 29, 2025.
The BLA is based on results from the pivotal TROPION-Breast01 phase 3 trial, which were presented at a Presidential Symposium at the European Society for Medical Oncology (#ESMO23) 2023 Congress and in an oral presentation at the 2023 San Antonio Breast Cancer Symposium (#SABCS23). In the trial, datopotamab deruxtecan demonstrated a statistically significant and clinically meaningful improvement for the dual primary endpoint of progression-free survival (PFS) compared to investigator’s choice of chemotherapy in patients with unresectable or metastatic HR positive, HER2 negative breast cancer previously treated with endocrine-based therapy and at least one systemic therapy. For the dual primary endpoint of overall survival (OS), interim results numerically favored datopotamab deruxtecan over chemotherapy but were not mature at the time of data cut-off. The trial is ongoing and OS will be assessed at future analyses. The safety profile of datopotamab deruxtecan was consistent with that observed in other ongoing trials with no new safety concerns identified. The most common grade 3 or higher treatment-related adverse events in the datopotamab deruxtecan and chemotherapy arms, respectively, were neutropenia (1% vs. 31%), stomatitis (6% vs. 3%), fatigue (2% vs. 2%) and anemia (1% vs. 2%). 2
“The FDA’s acceptance of the BLA brings us closer to providing patients with previously treated HR positive, HER2 negative breast cancer an alternative option to conventional chemotherapy earlier in the metastatic setting,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “Following our recently accepted application for advanced nonsquamous non-small cell lung cancer in the U.S., along with additional regulatory reviews underway in China, the EU, Japan and other regions, we are working swiftly to bring datopotamab deruxtecan as a potential new treatment option to patients around the world.”
“Despite marked progress in the treatment of HR positive, HER2 negative breast cancer, most patients with advanced disease develop endocrine resistance and face the prospect of one or several lines of chemotherapy,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D, AstraZeneca. “If approved, datopotamab deruxtecan has the potential to provide these patients an efficacious and better tolerated alternative to conventional chemotherapy.”
An additional BLA for datopotamab deruxtecan based on results from the pivotal TROPION-Lung01 phase 3 trial is under review in the U.S. for the treatment of adult patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) who have received prior systemic therapy. Additional regulatory submissions for datopotamab deruxtecan in lung and breast cancer are underway globally.
