• Application based on results from the TROPION-Breast01 phase 3 trial
• Additional BLA under review in the U.S. for Daiichi Sankyo and AstraZeneca’s datopotamab deruxtecanfor patients with advanced nonsquamous non-small cell lung cancer
Tokyo and Basking Ridge, NJ – (April 2, 2024) – 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 hormonereceptor (HR) positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have receivedprior 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) actiondate 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 aPresidential Symposium at the European Society for Medical Oncology (#ESMO23) 2023 Congress and inan oral presentation at the 2023 San Antonio Breast Cancer Symposium (#SABCS23). In the trial,datopotamab deruxtecan demonstrated a statistically significant and clinically meaningful improvement forthe dual primary endpoint of progression-free survival (PFS) compared to investigator’s choice ofchemotherapy in patients with unresectable or metastatic HR positive, HER2 negative breast cancerpreviously treated with endocrine-based therapy and at least one systemic therapy. For the dual primaryendpoint of overall survival (OS), interim results numerically favored datopotamab deruxtecan overchemotherapy but were not mature at the time of data cut-off. The trial is ongoing and OS will be assessed atfuture analyses. The safety profile of datopotamab deruxtecan was consistent with that observed in otherongoing trials with no new safety concerns identified. The most common grade 3 or higher treatment-relatedadverse 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 HRpositive, HER2 negative breast cancer an alternative option to conventional chemotherapy earlier in themetastatic setting,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “Following our recentlyaccepted application for advanced nonsquamous non-small cell lung cancer in the U.S., along with additionalregulatory reviews underway in China, the EU, Japan and other regions, we are working swiftly to bringdatopotamab 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 withadvanced disease develop endocrine resistance and face the prospect of one or several lines ofchemotherapy,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D,AstraZeneca. “If approved, datopotamab deruxtecan has the potential to provide these patients an efficaciousand better tolerated alternative to conventional chemotherapy.”
An additional BLA for datopotamab deruxtecan based on results from the pivotal TROPION-Lung01 phase 3trial is under review in the U.S. for the treatment of adult patients with locally advanced or metastaticnonsquamous non-small cell lung cancer (NSCLC) who have received prior systemic therapy. Additionalregulatory submissions for datopotamab deruxtecan in lung and breast cancer are underway globally.
About TROPION-Breast01
TROPION-Breast01 is a global, randomized, multicenter, open-label phase 3 trial evaluating the efficacy andsafety of datopotamab deruxtecan versus investigator’s choice of single-agent chemotherapy (eribulin,capecitabine, vinorelbine or gemcitabine) in patients with unresectable or metastatic HR positive, HER2negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have progressed on and are not suitable forendocrine therapy per investigator assessment and have received at least one additional systemic therapy forunresectable or metastatic disease.
The dual primary endpoints of TROPION-Breast01 are PFS as assessed by blinded independent centralreview and OS. Key secondary endpoints include objective response rate, duration of response, investigatorassessed PFS, disease control rate, time to first subsequent therapy and safety. TROPION-Breast01 enrolledmore than 700 patients in Africa, Asia, Europe, North America and South America. For more informationvisit ClinicalTrials.gov.
About Hormone Receptor Positive, HER2 Negative Breast Cancer
More than 275,000 breast cancer cases were diagnosed in the U.S. in 2022.1 HR positive, HER2 negativebreast cancer is the most common subtype, accounting for more than 65% of diagnosed cases.2 Breast canceris considered HR positive, HER2 negative when tumors test positive for estrogen and/or progesterone3hormone receptors and negative for HER2 (measured as HER2 score of IHC 0, IHC 1+ or IHC 2+/ISH-).2,3Standard initial treatment for this subtype of breast cancer is endocrine therapy but most patients withadvanced disease will develop resistance, underscoring the need for additional options.4,5
TROP2 is a protein broadly expressed in HR positive, HER2 negative breast cancer and is associated withincreased tumor progression and poor survival.6,7
About Datopotamab Deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2 directed ADC. Designed using DaiichiSankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in theoncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADCscientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonalantibody, developed in collaboration with Sapporo Medical University, attached to a number oftopoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
A comprehensive global clinical development program is underway with more than 20 trials evaluating theefficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple negativebreast cancer and HR positive, HER2 negative breast cancer.
About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercializeENHERTU in March 2019 and datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyomaintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply ofENHERTU and datopotamab deruxtecan.
About the DXd ADC Portfolio of Daiichi Sankyo
The DXd ADC portfolio of Daiichi Sankyo currently consists of six ADCs in clinical development acrossmultiple types of cancer. ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan, a TROP2directed ADC, are being jointly developed and commercialized globally with AstraZeneca. Patritumabderuxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC,and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed andcommercialized globally with Merck & Co., Inc., Rahway, N.J. USA. DS-3939, a TA-MUC1 directed ADC,is being developed by Daiichi Sankyo.
Designed using Daiichi Sankyo’s proprietary DXd ADC Technology to target and deliver a cytotoxicpayload inside cancer cells that express a specific cell surface antigen, each ADC consists of a monoclonal4antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) viatetrapeptide-based cleavable linkers.
Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan and DS-3939 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.
About Daiichi Sankyo
Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development ofsociety that discovers, develops and delivers new standards of care to enrich the quality of life around theworld. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science andtechnology to create new modalities and innovative medicines for people with cancer, cardiovascular andother diseases with high unmet medical need. For more information, please visit www.daiichisankyo.com.
References
1 World Health Organization. Global Cancer Observatory: United States of America. Accessed April 2024.
2 National Cancer Institute. SEER cancer stat facts: female breast cancer subtypes. Accessed April 2024.
3 Iqbal N, et al. Mol Biol Int. 2014;852748.
4 Lin M, et al. J Cancer. 2020; 10.7150/jca.48944.
5 Lloyd MR, et al. Clin Cancer Res. 2022;28(5):821-30.
6 Goldenberg D, et al. Oncotarget. 2018;9(48): 28989-29006.
7 Vidula N, et al. Breast Cancer Res Treat. 2022 Aug;194(3):569-575.