Daiichi Sankyo and AstraZeneca have dosed the first patient in the Phase 3 TROPION-Urothelial04 trial evaluating Datroway (datopotamab deruxtecan) in patients with high-risk muscle-invasive urothelial cancer following surgery, according to a press release issued by Daiichi Sankyo on August 26.
The global study is evaluating Datroway plus rilvegostomig, as well as Datroway monotherapy, against current standard-of-care adjuvant treatment in patients at high risk of disease recurrence after radical surgical resection, with or without previous neoadjuvant therapy.
Datroway is a TROP2-directed DXd antibody-drug conjugate developed jointly by Daiichi Sankyo and AstraZeneca. Rilvegostomig is an investigational bispecific antibody targeting the PD-1 and TIGIT immune checkpoints.
About the TROPION-Urothelial04 Trial
TROPION-Urothelial04 (NCT07720284) is a global, multicenter, open-label Phase 3 trial expected to enroll 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 plus rilvegostomig
- Datroway monotherapy
- Standard-of-care therapy with durvalumab, nivolumab, or enfortumab vedotin plus pembrolizumab
The trial includes patients with residual disease following neoadjuvant therapy and radical surgery, as well as patients with high-risk disease following surgery who did not receive neoadjuvant therapy.
The primary endpoint is investigator-assessed disease-free survival (DFS) for Datroway plus rilvegostomig compared with standard of care.
Key secondary endpoints include disease-free survival assessed by blinded independent central review, disease-specific survival, non-urothelial tract recurrence-free survival, distant metastasis-free survival, overall survival, patient-reported outcomes, and safety.
Expanding Datroway into Urothelial Cancer
Muscle-invasive urothelial cancer accounts for approximately 30% of urothelial cancer cases. Despite surgery and the availability of adjuvant immunotherapy, patients with high-risk disease can still experience recurrence, creating a need for additional postoperative treatment strategies. There are currently no TROP2-directed medicines approved for urothelial cancer, according to Daiichi Sankyo.
Abderrahmane Laadem, MD, Head of Therapeutic Area Oncology Development at Daiichi Sankyo, said the trial follows encouraging findings observed in urothelial cancer cohorts from the earlier TROPION-PanTumor03 and TROPION-PanTumor01 studies. He noted that TROPION-Urothelial04 represents the company’s second pivotal Datroway trial in urothelial cancer.
Daiichi Sankyo and AstraZeneca are also investigating Datroway in metastatic urothelial cancer in the TROPION-Urothelial03 Phase 2/3 trial, where Datroway plus platinum-based chemotherapy is being compared with gemcitabine plus platinum-based chemotherapy after progression during or following enfortumab vedotin plus pembrolizumab.
Datroway is already approved in several markets for indications in breast cancer and EGFR-mutated non-small cell lung cancer. Its broader clinical development program includes more than 20 studies across multiple tumor types, with TROPION-Urothelial04 extending development into the potentially curative adjuvant setting for high-risk muscle-invasive urothelial cancer.
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