AstraZeneca and Daiichi Sankyo’s Biologics License Application (BLA) for datopotamab deruxtecan (Dato-DXd) has been accepted and granted Priority Review in the US for the treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) who have received prior systemic therapies, including an EGFR-directed therapy.

The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance.¹ The Prescription Drug User Fee Act date, the FDA action date for its regulatory decision, is anticipated during the third quarter of 2025. Datopotamab deruxtecan was previously granted Breakthrough Therapy Designation (BTD) by the FDA for this patient population. 

The BLA and BTD are based on data from the TROPION-Lung05 Phase II trial and supported by data from the TROPION-Lung01 Phase III trial. In addition, the BLA is supported by data from the TROPION-PanTumor01 Phase I trial.

In a pooled analysis of patients with previously treated advanced or metastatic EGFRm NSCLC in the TROPION-Lung05 and TROPION-Lung01 trials presented at the European Society for Medical Oncology (ESMO) Asia 2024 Congress, datopotamab deruxtecan demonstrated a confirmed objective response rate (ORR) of 42.7% (95% confidence interval [CI] 33.6-52.2) as assessed by blinded independent central review (BICR) and a median duration of response (DoR) of 7.0 months (95% CI 4.2-9.8). The safety profile of datopotamab deruxtecan was consistent with previous reports from the TROPION-Lung05 and TROPION-Lung01 trials, with no new safety concerns identified. 

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “Acquired resistance to front-line therapies and, ultimately, disease progression are unfortunate realities for most patients with advanced EGFR-mutated non-small cell lung cancer. This Priority Review, and the previously granted Breakthrough Therapy Designation, recognise the potential for datopotamab deruxtecan to provide a much-needed option to patients whose disease has become resistant to current treatments.”  

Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: “Treating advanced EGFR-mutated non-small cell lung cancer presents a significant challenge due to the limited efficacy of available treatments once the disease has progressed following front-line therapies, including the use of an EGFR-tyrosine kinase inhibitor. If approved, datopotamab deruxtecan could become the first TROP2-directed antibody drug conjugate for lung cancer, providing a promising option for patients.”

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.

AstraZeneca and Daiichi Sankyo are evaluating datopotamab deruxtecan alone and in novel combinations as treatment for patients with NSCLC in seven Phase III trials including the TROPION-Lung14 and TROPION-Lung15 trials of datopotamab deruxtecan alone and with Tagrisso (osimertinib) as treatment for patients with advanced or metastatic EGFRm nonsquamous NSCLC.