Two datopotamab deruxtecan applications validated in the EU for patients with advanced nonsquamous non-small cell lung cancer 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. 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.

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.

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.”

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.


Advanced non-small cell lung cancer
Nearly 500,000 lung cancer cases were diagnosed in Europe in 2022.1 NSCLC is the most common type of lung cancer, accounting for about 80% of cases.1 Approximately 70% and 30% of NSCLC tumours are of nonsquamous or squamous histology, respectively.2 While immunotherapy and targeted therapies have improved outcomes in the first-line setting, most patients eventually experience disease progression and receive chemotherapy.3,4,5 For decades, chemotherapy has been the last treatment available for patients with advanced NSCLC, despite limited effectiveness and known side effects.3,4,5

HR-positive breast cancer
More than 500,000 breast cancer cases were diagnosed in Europe in 2022.6 HR-positive, HER2-negative breast cancer is the most common subtype, accounting for more than 65% of diagnosed cases.7 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-).7,8 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.9,10

TROP2 is a protein broadly expressed in several solid tumours, including the majority of NSCLC and HR-positive, HER2-negative breast cancer cases.11,12 High TROP2 expression is associated with increased tumour progression and poor survival.12,13 There is currently no TROP2-directed ADC approved for the treatment of lung cancer.14,15

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.

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