EMA Tests MAAs for Datopotamab Deruxtecan

EMA validates two MAAs for AstraZeneca & Daiichi Sankyo’s datopotamab deruxtecan for advanced nonsquamous NSCLC or HR-positive, HER2-negative breast cancer

The European Medicines Agency (EMA) has validated two marketing authorisation applications (MAAs) for AstraZeneca and Daiichi Sankyo’s datopotamab deruxtecan (Dato-DXd) in two types of cancer. One MAA is for the treatment of adult patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) who require systemic therapy following prior treatment.

MAA for Breast Cancer

The other MAA is 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 progressed on and are not suitable for endocrine therapy and received at least one additional systemic therapy.

Results 

The validations confirm the completion of the applications and commence the scientific review process by the EMA’s Committee for Medicinal Products for Human Use. The applications are based on data from the pivotal TROPION-Lung01 and TROPION-Breast01 phase III trials presented during two Presidential Symposia at the 2023 European Society for Medical Oncology Congress.

About Datopotamab Deruxtecan

• 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: “Our ambition is for datopotamab deruxtecan to improve upon and replace conventional chemotherapy in the treatment of multiple cancer types. Today’s dual validation of our applications in lung and breast cancers brings this potential medicine a meaningful step closer to redefining treatment expectations for patients with two of the most common cancers in Europe.”

From Head: Daiichi Sankyo

• Ken Takeshita, MD, global head, R&D, Daiichi Sankyo, said: “The EMA validation is an important first step toward bringing this TROP2-directed antibody drug conjugate to eligible patients in Europe with nonsquamous lung cancer and HR-positive, HER2-negative breast cancer. 
• This news builds on our recent regulatory progress in the US, where our lung cancer application has been accepted and our breast cancer application is underway, underscoring our commitment to changing the standard of care by developing new medicines to help as many patients worldwide as possible."

Additional regulatory submissions for datopotamab deruxtecan in lung cancer and breast cancer are underway in the US and globally.

Lung Cancer: Epidemiology

• Nearly 500,000 lung cancer cases were diagnosed in Europe in 2022. 
• NSCLC is the most common type of lung cancer, accounting for about 80% of cases. 
• Approximately 70% and 30% of NSCLC tumours are of nonsquamous or squamous histology, respectively. 
• While immunotherapy and targeted therapies have improved outcomes in the first-line setting, most patients eventually experience disease progression and receive chemotherapy. 
• For decades, chemotherapy has been the last treatment available for patients with advanced NSCLC, despite limited effectiveness and known side effects.  

Breast Cancer: Epidemiology

• More than 500,000 breast cancer cases were diagnosed in Europe in 2022. 
• HR-positive, HER2-negative breast cancer is the most common subtype, accounting for more than 65% of diagnosed cases. 
• 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-). 
• 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.

AAbout TROP2

• TROP2 is a protein broadly expressed in several solid tumours, including the majority of NSCLC and HR-positive, HER2-negative breast cancer cases. 
• High TROP2 expression is associated with increased tumour progression and poor survival. There is currently no TROP2-directed ADC approved for the treatment of lung cancer.

TROPION-Lung01 Trials

• TROPION-Lung01 is a global, randomised, multicentre, open-label phase III trial evaluating the efficacy and safety of datopotamab deruxtecan versus docetaxel in patients with locally advanced or metastatic NSCLC with and without actionable genomic alterations who require systemic therapy following prior treatment. 
• Patients with actionable genomic alterations were previously treated with platinum-based chemotherapy and an approved targeted therapy. 
• Patients without known actionable genomic alterations were previously treated, either in combination or sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor.
• The dual primary endpoints of TROPION-Lung01 are progression-free survival (PFS) as assessed by blinded independent central review (BICR) and overall survival (OS). 
• Key secondary endpoints include investigator-assessed PFS, objective response rate (ORR), duration of response (DoR), time to response, disease control rate (DCR) as assessed by both BICR and investigator, and safety. 
• TROPION-Lung01 enrolled approximately 600 patients in Asia, Europe, North America and South America.

TROPION-Breast01 Trials

• 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 BICR and OS. 
• Key secondary endpoints include ORR, DoR, investigator-assessed PFS, DCR, time to first subsequent therapy and safety. TROPION-Breast01 enrolled more than 700 patients in Africa, Asia, Europe, North America and South America.

Companies Behind the Drug

• 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 humanized 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.

Other Trials

A comprehensive development programme called TROPION is underway globally with more than 14 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple-negative breast cancer and HR-positive, HER2-negative breast cancer. Beyond the TROPION programme, datopotamab deruxtecan also is being evaluated in novel combinations in several ongoing trials.

About Partnership

• AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu in March 2019 and datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. 
• Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and datopotamab deruxtecan.

About AstraZeneca

AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

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