The European Commission has approved Datroway (datopotamab deruxtecan) as monotherapy for the 1st-line treatment of adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy — making it the second breast cancer indication for the antibody-drug conjugate (ADC) in the EU, and the first TROP2-directed therapy in this setting to demonstrate an overall survival (OS) benefit.
The decision follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) and mirrors a US FDA approval granted in May 2026 for the same indication. Regulatory reviews are underway in China, Japan, Australia, Canada, Singapore, and Switzerland under Project Orbis.
The approval is supported by TROPION-Breast02 (NCT05374512), a global, randomised, open-label Phase III trial enrolling 644 patients with previously untreated locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option. The trial carried dual primary endpoints of OS and progression-free survival (PFS) assessed by blinded independent central review (BICR). Datroway demonstrated a statistically significant 5.0-month improvement in median OS compared to investigator's choice of chemotherapy — 23.7 months versus 18.7 months (hazard ratio 0.79; 95% confidence interval 0.64–0.98; p=0.0291). The drug also reduced the risk of disease progression or death by 43% (HR 0.57; 95% CI 0.47–0.69; p<0.0001) and produced an objective response rate (ORR) of 62.5% versus 29.3% with chemotherapy. Results were presented at the 2025 European Society for Medical Oncology (ESMO) Congress and published in Annals of Oncology.
Datroway consists of a humanized anti-TROP2 IgG1 monoclonal antibody conjugated via tetrapeptide-based cleavable linkers to DXd, an exatecan-derived topoisomerase I inhibitor, using Daiichi Sankyo's proprietary DXd ADC platform. Following receptor-mediated internalization, intracellular linker cleavage releases the payload, inducing DNA damage and apoptosis, with a bystander killing effect on adjacent tumor cells.