The US Food and Drug Administration (FDA) granted accelerated approval to the antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) on November 11, 2026. Daiichi Sankyo and AstraZeneca jointly developed the TROP2-directed ADC for adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who received prior systemic therapies. The FDA action makes it the first TROP2-directed antibody-drug conjugate approved for pulmonary oncology indications.
The accelerated approval was based on objective response metrics and progression-free survival (PFS) from the global Phase 3 TROPION-Lung01 trial, which enrolled more than 600 advanced lung cancer patients whose disease progressed after platinum-based doublet chemotherapy and anti-PD-(L)1 immune checkpoint inhibitor regimens. Dato-DXd achieved a statistically significant 25 percent reduction in the risk of disease progression or death compared with standard docetaxel monotherapy. Among non-squamous patients with high TROP2 expression, Dato-DXd extended median PFS to 5.6 months and produced an objective response rate of 31.2 percent.
According to the Journal of Clinical Oncology and Reuters, AstraZeneca Executive Vice President of Oncology R&D Susan Galbraith said at a briefing: Patients with refractory advanced non-small cell lung cancer historically faced dismal prognoses with toxic second-line chemotherapy. Dato-DXd uses Daiichi Sankyo's proprietary DXd platform, linking a humanized anti-TROP2 IgG1 monoclonal antibody to an exatecan-derived topoisomerase I inhibitor via a tetrapeptide cleavable linker. FDA pharmacovigilance reviewers noted Grade 3 or higher treatment-related hematologic toxicities occurred at half the rate in the docetaxel comparator arm; black-box warnings highlight interstitial lung disease (ILD) and non-infectious pneumonitis, and prescribers must implement mandatory high-resolution chest computed tomography monitoring throughout active treatment cycles.
The partners confirmed technical submissions with the European Medicines Agency (EMA) and Japan's Ministry of Health, Labour and Welfare (MHLW), and oncology trial sites are enrolling patients in Phase 3 trials evaluating Dato-DXd in combination with PD-1 inhibitors for solid tumors.
