Tokyo, August 26, 2026
Daiichi Sankyo announced that the first patient has been dosed in TROPION-Urothelial04, a global Phase 3 trial evaluating Datroway® (datopotamab deruxtecan) as an adjuvant treatment for patients with high-risk muscle invasive urothelial cancer (MIUC) following radical surgical resection. The study will evaluate Datroway plus rilvegostomig, Datroway monotherapy, and current standard-of-care treatments, including durvalumab, nivolumab, or enfortumab vedotin plus pembrolizumab. The trial represents an important expansion of Daiichi Sankyo and AstraZeneca’s clinical development program for Datroway into an earlier-stage urothelial cancer setting, where preventing recurrence after surgery remains a major treatment challenge. MIUC is an aggressive form of urothelial cancer associated with a substantial risk of recurrence despite advances in adjuvant immunotherapy. TROPION-Urothelial04 is therefore designed to generate pivotal evidence on whether a TROP2-directed antibody-drug conjugate (ADC) can improve outcomes in patients at high risk of disease returning after surgery.
TROPION-Urothelial04 Targets High-Risk Disease After Surgery
Daiichi Sankyo is conducting TROPION-Urothelial04 as a global, multicenter, open-label Phase 3 trial enrolling approximately 915 patients across Asia, Europe, North America, Oceania and South America. Participants will be randomized in a 2:1:2 ratio to receive Datroway in combination with rilvegostomig, Datroway monotherapy, or investigator-selected current standard of care. The study is focused on patients with high-risk MIUC, including individuals with residual disease identified during surgical resection following neoadjuvant therapy and patients with high-risk disease after surgery without prior neoadjuvant treatment. The primary endpoint is investigator-assessed disease-free survival (DFS) comparing Datroway plus rilvegostomig with standard of care. Key secondary measures include DFS assessed by blinded independent central review, disease-specific survival, non-urothelial tract recurrence-free survival, distant metastasis-free survival, patient-reported outcomes, overall survival and safety. The trial structure gives Daiichi Sankyo an opportunity to evaluate Datroway across both combination and monotherapy approaches while directly comparing the investigational strategies with established treatment options.
Datroway Expands TROP2-Directed ADC Development
Daiichi Sankyo and AstraZeneca are positioning Datroway as a broad oncology development program, with more than 20 clinical trials evaluating the ADC across multiple tumor types. Datroway is a TROP2-directed ADC built using Daiichi Sankyo’s proprietary DXd ADC Technology, consisting of a humanized anti-TROP2 monoclonal antibody linked to topoisomerase I inhibitor payloads through cleavable linkers. TROP2 is broadly expressed across several solid tumors, including urothelial cancer, making it a relevant target for ADC-based treatment development. The companies previously observed encouraging findings in urothelial cancer cohorts from the TROPION-PanTumor03 and TROPION-PanTumor01 trials, supporting further evaluation in the disease. TROPION-Urothelial04 is the companies’ second pivotal urothelial cancer trial involving Datroway, while TROPION-Urothelial03 is evaluating Datroway plus platinum-based chemotherapy in metastatic urothelial cancer following progression after enfortumab vedotin plus pembrolizumab. Together, these studies expand the clinical investigation of Datroway across different stages and treatment settings of urothelial cancer.
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Phase 3 Program Addresses Recurrence and Unmet Need
Daiichi Sankyo is advancing TROPION-Urothelial04 against a significant unmet need in muscle invasive urothelial cancer, which represents approximately 30% of urothelial cancer cases. Although adjuvant immunotherapy is an established treatment approach, a considerable proportion of patients remain at risk of recurrence after radical surgery. The new Phase 3 study is intended to determine whether targeting TROP2 with Datroway, either alone or alongside the dual checkpoint inhibitor rilvegostomig, can provide a more effective strategy for reducing recurrence and improving long-term outcomes. Rilvegostomig combines PD-1 and TIGIT checkpoint inhibition, adding an immune-based mechanism to the ADC approach. Daiichi Sankyo’s broader Datroway program currently includes Phase 3 studies across lung cancer, breast cancer and urothelial cancer, reflecting the company’s strategy of expanding the ADC into multiple solid tumors. The initiation of TROPION-Urothelial04 therefore marks a significant clinical development milestone for Datroway in urothelial cancer, with the approximately 915-patient study now moving into pivotal evaluation of disease-free survival and longer-term patient outcomes.
Source:Daiichi Sankyo press relese
