FDA Accepts Biologics License Application for Datopotamab Deruxtecan in Previously Treated Advanced Nonsquamous Non-Small Cell Lung Cancer
Monday, February 19, 2024
Daiichi Sankyo (TSE: 4568) and AstraZeneca’s (LSE/STO/Nasdaq: AZN) Biologics License Application (BLA) for datopotamab deruxtecan (Dato-DXd) has been accepted in the United States for the treatment of adult patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) who have previously received systemic therapy.
Datopotamab deruxtecan is a specially engineered antibody drug conjugate (ADC) that targets TROP2, jointly developed by Daiichi Sankyo and AstraZeneca.
The Prescription Drug User Fee Act (PDUFA) date, the U.S. Food and Drug Administration (FDA) action date for its regulatory decision, is December 20, 2024.
The BLA is supported by results from the pivotal TROPION-Lung01 phase 3 trial presented at a Presidential Symposium at the European Society for Medical Oncology (#ESMO23) 2023 Congress. In this trial, datopotamab deruxtecan showed a statistically significant improvement in progression-free survival (PFS) compared to docetaxel, the current standard of care, in patients with locally advanced or metastatic NSCLC who had received at least one prior line of therapy. While the interim results for overall survival (OS) favored datopotamab deruxtecan over docetaxel, statistical significance was not reached at the time of data cut-off. However, in patients with nonsquamous NSCLC, datopotamab deruxtecan demonstrated a clinically meaningful benefit in PFS and a positive trend in OS. The trial is ongoing, with OS to be assessed at final analysis. The safety profile of datopotamab deruxtecan remained consistent with that observed in other ongoing trials, with no new safety concerns identified.
Daiichi Sankyo, expressed enthusiasm about the FDA's acceptance of the BLA, emphasizing the potential of datopotamab deruxtecan to become the first approved TROP2-directed ADC for nonsquamous NSCLC patients after disease progression on prior systemic therapy. Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, highlighted the potential of datopotamab deruxtecan as an effective and tolerable alternative to conventional chemotherapy for previously treated advanced nonsquamous NSCLC patients.
Additionally, a parallel BLA for datopotamab deruxtecan based on the TROPION-Breast01 phase 3 trial is pending acceptance in the U.S. for the treatment of adult patients with metastatic hormone receptor (HR) positive, HER2 negative breast cancer. Further regulatory submissions for datopotamab deruxtecan in lung and breast cancer are ongoing worldwide.
The TROPION-Lung01 trial is a global, randomized, multicenter, open-label phase 3 trial comparing datopotamab deruxtecan to docetaxel in patients with locally advanced or metastatic NSCLC, with and without actionable genomic alterations, who have previously received at least one prior line of therapy. The trial's primary endpoints are PFS and OS, with key secondary endpoints including objective response rate, duration of response, and safety. The trial enrolled approximately 600 patients across multiple regions.
With nearly 250,000 lung cancer cases diagnosed in the U.S. in 2023, NSCLC represents the most common type of lung cancer, comprising about 80% of cases. While immunotherapy and targeted therapies have improved outcomes in the first-line setting, chemotherapy remains the last treatment option for many patients with advanced NSCLC. TROP2, a protein broadly expressed in the majority of NSCLC tumors, presents an attractive target for novel therapies like datopotamab deruxtecan.
Datopotamab deruxtecan, developed using Daiichi Sankyo's proprietary DXd ADC Technology, consists of a humanized anti-TROP2 IgG1 monoclonal antibody linked to a topoisomerase I inhibitor payload via cleavable linkers. It is part of the broader TROPION development program, encompassing more than 14 trials evaluating its efficacy and safety across multiple cancers, including NSCLC, triple-negative breast cancer, and HR-positive, HER2-negative breast cancer. Additionally, datopotamab deruxtecan is being investigated in novel combinations in several ongoing trials.
Source: businesswire.com
