The US FDA has approved Datroway (datopotamab deruxtecan-dlnk), a TROP2-directed antibody-drug conjugate co-developed by Daiichi Sankyo and AstraZeneca, for adult patients with unresectable or metastatic triple-negative breast cancer who are not candidates for PD-1/PD-L1 inhibitor therapy — a first-line population that has historically been limited to cytotoxic chemotherapy.
The approval covers patients who have not received prior chemotherapy or systemic anti-cancer therapy for unresectable or metastatic disease. The recommended dose is 6 mg/kg administered intravenously once every three weeks, with a maximum of 540 mg for patients weighing 90 kg or more. The application received priority review and was evaluated under Project Orbis, a framework enabling concurrent review with international regulatory partners including Health Canada, Australia’s TGA, Brazil’s ANVISA, Singapore’s HSA, and Switzerland’s Swissmedic.
Clinical evidence from TROPION-Breast02
Approval was supported by TROPION-Breast02 (NCT05374512), a Phase III multicenter, open-label, randomized trial enrolling 644 patients with unresectable or metastatic TNBC who were ineligible for PD-1/PD-L1 inhibitor therapy. Patients were randomized 1:1 to datopotamab deruxtecan-dlnk or investigator’s choice of chemotherapy, which included nab-paclitaxel (54%), paclitaxel (28%), eribulin (11%), carboplatin (4.7%), and capecitabine (2.2%). The co-primary endpoints were progression-free survival and overall survival assessed by blinded independent central review.
Median PFS was 10.8 months in the Datroway arm versus 5.6 months in the chemotherapy arm (HR 0.57; 95% CI: 0.47–0.69; p < 0.0001). Median OS was 23.7 months versus 18.7 months (HR 0.79; 95% CI: 0.64–0.98; p=0.0290). Confirmed overall response rate was 64% versus 30%.