La FDA acepta Dato-DXd BLA para el cáncer de mama
Renk AG
n / a
07:46 20/03/24
2 de abril de 2024
Datopotamab deruxtecan Biologics License Application accepted in the US for patients with previously treated metastatic HR-positive, HER2-negative breast cancer
Application based on results from the TROPION-Breast01 Phase III trial
Additional BLA under review in the US for AstraZeneca and Daiichi Sankyo's datopotamab deruxtecan for patients with advanced nonsquamous non-small cell lung cancer
AstraZeneca and Daiichi Sankyo's Biologics License Application (BLA) for datopotamab deruxtecan (Dato-DXd) has been accepted in the US 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. The Prescription Drug User Fee Act date, the US Food and Drug Administration (FDA) action date for its regulatory decision, is during the first quarter of 2025.
The BLA is based on results from the pivotal TROPION-Breast01 Fase III trial in which 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 favoured 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.
Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed by AstraZeneca and Daiichi Sankyo.
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "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. If approved, datopotamab deruxtecan has the potential to provide these patients an efficacious and better tolerated alternative to conventional chemotherapy."
Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: "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. Following our recently accepted application for advanced nonsquamous non-small cell lung cancer in the US, 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."
Los resultados de los TROPION-Mama01 were presented during a Presidential Symposium at the 2023 European Society for Medical Oncology Congress and in an oral presentation at the 2023 San Antonio Breast Cancer Symposium.
The safety profile of datopotamab deruxtecan was consistent with that observed in other ongoing trials with no new safety concerns identified.
An additional BLA for datopotamab deruxtecan based on results from the pivotal TROPION-Lung01 Phase III trial is under review in the US 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.
Notas
Cáncer de mama HR positivo
More than 275,000 breast cancer cases were diagnosed in the US in 2022.1 HR-positive, HER2-negative breast cancer is the most common subtype, accounting for more than 65% of diagnosed cases.2 Breast cancer is considered HR-positive, HER2-negative when tumours test positive for oestrogen and/or progesterone hormone receptors and negative for HER2 (measured as HER2 score of IHC 0, IHC 1+ or IHC 2+/ISH-).2,3 Standard initial treatment for this subtype of breast cancer is endocrine therapy but most patients with advanced 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 with increased tumour progression and poor survival.6,7
TROPION-Mama01
TROPION-Breast01 is a global, randomised, multicentre, open-label Phase III trial evaluating the efficacy and safety of datopotamab deruxtecan versus investigator's choice of single-agent chemotherapy (eribulin, capecitabine, vinorelbine or gemcitabine) in patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have progressed on and are not suitable for endocrine therapy per investigator assessment and have received at least one additional systemic therapy for unresectable or metastatic disease.
The dual primary endpoints of TROPION-Breast01 are PFS as assessed by blinded independent central review (BICR) and OS. Key secondary endpoints include objective response rate, duration of response, investigator-assessed PFS, disease control rate, time to first subsequent therapy and safety. TROPION-Breast01 enrolled more than 700 patients in Africa, Asia, Europe, North America and South America. For more information visit ClinicalTrials.gov.
Datopotamab deruxtecán (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2-directed ADC. Designed using Daiichi Sankyo's proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programmes in AstraZeneca's ADC scientific platform. Datopotamab deruxtecan is comprised of a humanised anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
A comprehensive global clinical development programme is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple-negative breast cancer (TNBC) and HR-positive, HER2-negative breast cancer.
Colaboración con Daiichi Sankyo
AstraZeneca y Daiichi Sankyo iniciaron una colaboración global para desarrollar y comercializar conjuntamente Enhertu in Marzo 2019 y datopotamab deruxtecan en Julio 2020, excepto en Japón donde Daiichi Sankyo mantiene derechos exclusivos para cada ADC. Daiichi Sankyo es responsable de la fabricación y suministro de Enhertu y datopotamab deruxtecan.
AstraZeneca en cáncer de mama
Impulsada por una comprensión cada vez mayor de la biología del cáncer de mama, AstraZeneca está comenzando a desafiar y redefinir el paradigma clínico actual sobre cómo se clasifica y trata el cáncer de mama para brindar tratamientos aún más efectivos a los pacientes que lo necesitan, con la audaz ambición de eliminar algún día El cáncer de mama como causa de muerte.
AstraZeneca tiene una cartera integral de compuestos aprobados y prometedores en desarrollo que aprovechan diferentes mecanismos de acción para abordar el entorno tumoral de cáncer de mama biológicamente diverso.
Con Enhertu (trastuzumab deruxtecan), un ADC dirigido por HER2, AstraZeneca y Daiichi Sankyo tienen como objetivo mejorar los resultados en el cáncer de mama metastásico HER2 positivo y HER2 bajo previamente tratado y están explorando su potencial en líneas de tratamiento anteriores y en nuevos entornos de cáncer de mama.
En cáncer de mama HR positivo, AstraZeneca continúa mejorando los resultados con medicamentos básicos Faslodex y Zoladex (goserelina) y tiene como objetivo remodelar el espacio HR positivo con el primer inhibidor de AKT de su clase, Truqap, y SERD de próxima generación y un posible nuevo medicamento camizestrant. AstraZeneca también está colaborando con Daiichi Sankyo para explorar el potencial del ADC dirigido por TROP2, datopotamab deruxtecan, en este entorno.
Inhibidor de PARP lynparza (olaparib) es una opción de tratamiento dirigida que se ha estudiado en pacientes con cáncer de mama metastásico y temprano con una mutación BRCA hereditaria. AstraZeneca con MSD (Merck & Co., Inc. en EE. UU. y Canadá) continúan investigando lynparza en estos entornos y explorar su potencial en enfermedades más tempranas.
To bring much-needed treatment options to patients with TNBC, an aggressive form of breast cancer, AstraZeneca is evaluating the potential of datopotamab deruxtecan alone and in combination with immunotherapy Imfinzi (durvalumab), Truqap in combination with chemotherapy, and Imfinzi en combinación con otros medicamentos oncológicos, incluidos lynparza y Enhertu.
AstraZeneca en oncología
AstraZeneca está liderando una revolución en oncología con la ambición de proporcionar curas para el cáncer en todas sus formas, siguiendo la ciencia para comprender el cáncer y todas sus complejidades para descubrir, desarrollar y entregar medicamentos que cambian la vida de los pacientes.
El enfoque de la Compañía está en algunos de los cánceres más desafiantes. Es a través de la innovación persistente que AstraZeneca ha construido una de las carteras y proyectos más diversos de la industria, con el potencial de catalizar cambios en la práctica de la medicina y transformar la experiencia del paciente.
AstraZeneca tiene la visión de redefinir la atención del cáncer y, algún día, eliminar el cáncer como causa de muerte.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, Respiratory & Immunology and Vaccines & Immune Therapies. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com y sigue a la Compañía en las redes sociales @AstraZeneca.
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Referencias
1. World Health Organization. Global Cancer Observatory: United States of America. Available at: https://gco.iarc.who.int/media/globocan/factsheets/populations/840-united-states-of-america-fact-sheet.pdf. Consultado en abril de 2024.
2. National Cancer Institute. SEER cancer stat facts: female breast cancer subtypes. Available at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html. Consultado en abril de 2024.
3. Iqbal N, et al. Receptor 2 del factor de crecimiento epidérmico humano (HER2) en cánceres: sobreexpresión e implicaciones terapéuticas. Mol Biol Int.. 2014; 852748.
4. Lin M, et al. Comparative Overall Survival of CDK4/6 Inhibitors Plus Endocrine Therapy vs. Endocrine Therapy Alone for Hormone receptor-positive, HER2-negative metastatic breast cancer. j cáncer. 2020; 10.7150/jca.48944.
5. Lloyd MR, et al. Mechanisms of Resistance to CDK4/6 Blockade in Advanced Hormone Receptor-positive, HER2-negative Breast Cancer and Emerging Therapeutic Opportunities. Clin Cancer Nada. 2022; 28 (5): 821-30.
6. Goldenberg D, et al. La aparición del antígeno 2 de la superficie celular del trofoblasto (TROP-2) como un nuevo objetivo del cáncer. Oncotarget. 2018;9(48): 28989-29006.
7. Vidula N, et al. Sacituzumab govitecan: Antibody-drug conjugate in triple negative breast cancer and other solid tumours. Tratamiento para el cáncer de mama. 2022 Aug;194(3): 569-575.
Adrián Kemp
Secretaria de Empresa
AstraZenecaPLC
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