FDA Accepts Datopotamab Deruxtecan BLA for Nonsquamous NSCLC Treatment
Key Insights
The FDA has accepted the Biologics License Application (BLA) for datopotamab deruxtecan for treating advanced nonsquamous non-small cell lung cancer (search) (NSCLC (search)).
The BLA is based on the TROPION-Lung01 Phase III trial, which showed statistically significant improvement in progression-free survival (PFS) compared to docetaxel.
Datopotamab deruxtecan is a TROP2 (search)-directed antibody-drug conjugate (ADC) developed by AstraZeneca and Daiichi Sankyo, potentially the first of its kind approved for NSCLC (search).
The FDA has accepted AstraZeneca and Daiichi Sankyo’s Biologics License Application (BLA) for datopotamab deruxtecan (Dato-DXd) for the treatment of adult patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (search) (NSCLC (search)) who have received prior systemic therapy. The Prescription Drug User Fee Act (PDUFA) date, the FDA action date for its regulatory decision, is scheduled for the fourth quarter of 2024.
The BLA submission is supported by data from the pivotal TROPION-Lung01 Phase III trial, which demonstrated a statistically significant improvement in progression-free survival (PFS) compared to docetaxel, the current standard of care. Interim overall survival (OS) results numerically favored datopotamab deruxtecan, although statistical significance was not reached at the data cut-off. The trial is ongoing, with final OS analysis pending.
TROPION-Lung01 Trial Details
TROPION-Lung01 is a global, randomized, multicenter, open-label Phase III trial evaluating datopotamab deruxtecan versus docetaxel in patients with locally advanced or metastatic NSCLC (search), both with and without actionable genomic alterations, who have previously received at least one line of therapy. The dual primary endpoints are PFS, assessed by blinded independent central review (BICR), and OS. Key secondary endpoints include investigator-assessed PFS, objective response rate, duration of response, and safety. The trial enrolled approximately 600 patients across Asia, Europe, North America, and South America.
Datopotamab Deruxtecan: A Novel TROP2-Directed ADC
Datopotamab deruxtecan is an investigational TROP2 (search)-directed antibody-drug conjugate (ADC) utilizing Daiichi Sankyo’s proprietary DXd ADC Technology. It comprises a humanized anti-TROP2 IgG1 monoclonal antibody linked to a topoisomerase I inhibitor payload (DXd). TROP2 is a protein broadly expressed in the majority of NSCLC (search) tumors, making it a promising target for ADC therapy. Currently, there are no approved TROP2-directed ADCs for lung cancer (search) treatment.
Clinical Significance and Market Landscape
Lung cancer (search) remains a significant global health challenge, with nearly 250,000 cases diagnosed in the US in 2023. NSCLC (search) accounts for approximately 80% of all lung cancer cases, with nonsquamous histology representing about 70% of NSCLC tumors. While immunotherapy and targeted therapies have improved outcomes in the first-line setting, most patients eventually experience disease progression and require chemotherapy. Datopotamab deruxtecan offers a potential alternative to conventional chemotherapy, addressing an unmet need in patients with previously treated advanced nonsquamous NSCLC.
Ongoing Development and Future Prospects
AstraZeneca and Daiichi Sankyo are jointly developing and commercializing datopotamab deruxtecan, with Daiichi Sankyo responsible for manufacturing and supply. A comprehensive development program, TROPION, is underway, encompassing over 14 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC (search), triple-negative breast cancer, and HR-positive, HER2-negative breast cancer. A parallel BLA for datopotamab deruxtecan is also pending acceptance in the US for metastatic HR-positive, HER2-negative breast cancer, based on the TROPION-Breast01 Phase III trial results.