AstraZeneca & Daiichi Sankyo Voluntarily Withdraw EU Submission for Lung Cancer Drug

AstraZeneca and Daiichi Sankyo have announced they will withdraw their marketing authorisation application (MAA) in the European Union for datopotamab deruxtecan (Dato-DXd). The application aimed to secure approval for the treatment of adults with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC). The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) provided feedback that led to this decision. Clinical data from the TROPION-Lung01 Phase III trial supported the submission.

Dato-DXd Did Not Show Statistically Significant Improvement in Overall Survival Compared to Docetaxel

The Phase III TROPION-Lung01 trial served as the basis for the application, assessing the efficacy and safety of Dato-DXd in comparison to docetaxel, a standard chemotherapy treatment used for patients with NSCLC. This global, randomized, multicenter, open-label study included approximately 600 participants from Asia, Europe, North America, Oceania, and South America. It enrolled patients with and without actionable genomic alterations who had undergone prior systemic therapy, including targeted therapy and platinum-based chemotherapy for those with genomic alterations, or platinum-based chemotherapy with a PD-1 or PD-L1 inhibitor for those without.

The trial’s dual primary endpoints were progression-free survival (PFS), assessed by blinded independent central review (BICR), and overall survival (OS). Secondary endpoints included investigator-assessed PFS, objective response rate, duration of response, time to response, disease control rate, and safety outcomes. 

Results presented at the European Society for Medical Oncology (ESMO) 2023 Congress showed that Dato-DXd significantly improved PFS compared to docetaxel, with patients receiving Dato-DXd experiencing a median PFS of 6.2 months versus 4.8 months for those on docetaxel. However, the trial did not demonstrate a statistically significant improvement in OS, with median OS for Dato-DXd at 12.5 months compared to 11.8 months for docetaxel. Therefore, whilst Dato-DXd demonstrated a significant improvement in PFS compared to docetaxel, it did not show a meaningful difference in OS, indicating that although the drug delayed disease progression, it did not extend the patients’ lifespan in a statistically significant way.

Over 20 Global Clinical Trials Currently Evaluating the Efficacy and Safety of Dato-DXd for NSCLC and Other Cancers

In 2022, nearly 2.5 million lung cancer cases were diagnosed globally, with almost half a million of those cases occurring in Europe. Lung cancer divides into small cell lung cancer and non-small cell lung cancer (NSCLC), with NSCLC making up about 80% of cases. Although immunotherapy and targeted therapies have improved outcomes in the first-line setting, most patients ultimately experience disease progression and require chemotherapy. Despite its limited effectiveness and known side effects, chemotherapy has remained the last available treatment option for advanced NSCLC for decades.

Daiichi Sankyo developed Dato-DXd as an investigational TROP2-directed antibody-drug conjugate (ADC) using their proprietary DXd ADC technology. It is one of six DXd ADCs in Daiichi Sankyo’s oncology pipeline and is among the most advanced programs in AstraZeneca’s ADC scientific platform. Dato-DXd consists of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, linked to multiple topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Based on its promising early results, Dato-DXd is undergoing extensive clinical trials to further assess its effectiveness and safety in treating various types of cancer. The global development program includes more than 20 trials, focusing on cancers such as NSCLC, triple-negative breast cancer (TNBC), and HR-positive, HER2-negative breast cancer. Seven Phase III trials will target lung cancer, while five will focus on breast cancer, testing Dato-DXd both as a monotherapy and in combination with other cancer treatments across different clinical settings. 

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Author

Denisse Sandoval