A Phase III, Open-Label, Randomised, Multicentre, Global Study of Adjuvant Datopotamab Deruxtecan in Combination With Rilvegostomig in Participants With High-risk Muscle Invasive Urothelial Carcinoma.

Trial details

Who runs it

AstraZeneca AB

Trial code

EU 2025-525030-57-00

Record updated

2026. szeptember 28.

Original description

To demonstrate the superiority of Dato DXd + rilvegostomig (Arm 1) versus standard of care (Arm 3: nivolumab or durvalumab or EV + pembrolizumab) by disease free survival (DFS) per RECIST 1.1 as assessed by the Investigator in participants with high risk residual MIUC after radical resection.Read full original descriptionShow less

A Phase III, Open-Label, Randomised, Multicentre, Global Study of Adjuvant Datopotamab Deruxtecan in Combination With Rilvegostomig in Participants With High-risk Muscle Invasive Urothelial Carcinoma (TROPION-Urothelial04).

To demonstrate the superiority of Dato DXd + rilvegostomig (Arm 1) versus standard of care (Arm 3: nivolumab or durvalumab or EV + pembrolizumab) by disease free survival (DFS) per RECIST 1.1 as assessed by the Investigator in participants with high risk residual MIUC after radical resection.

Inclusion: Participant must be > 18 years of age at the time of signing the ICF; Histologically confirmed MIUC of the bladder or upper tract; Completed R0 radical resection 28 to 120 days before randomisation, with negative margins and no residual or metastatic disease; Pathologic evidence of urothelial carcinoma at high-risk of recurrence and (a) not received neoadjuvant therapy and has pT3–pT4aN0, or any pT with pN+ stage; (b) completed neoadjuvant treatment and has ypT2–ypT4a, or any ypT with ypN+ stage; No evidence of disease at screening; ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to randomisation; Minimum life expectancy of > 12 weeks at time of screening; An archival surgical tumour sample must be available prerandomisation for central testing; Adequate organ and bone marrow function within 28 days before randomisation.

Exclusion: Active or prior documented autoimmune or inflammatory disorders requiring systemic treatment in the past 5 years; Prior exposure to TROP2-directed therapies, other ADCs with deruxtecan, therapeutic anti-cancer vaccines, anti-TIGIT therapy or any other anti-cancer therapy targeting immuneregulatory receptors or mechanisms; Current or prior use of immunosuppressive medication within 14 days prior to treatment assignment/randomisation; Any adjuvant systemic or radiation therapy post-surgery for urothelial carcinoma; History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 2 years before the first dose of study intervention and of low potential risk for recurrence; Any other active or uncontrolled infection including tuberculosis requiring systemic treatment that has not resolved by the time of randomisation; History of non-infectious ILD/pneumonitis including radiation, pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening; Uncontrolled or significant cardiac conditions; Known history of severe hypersensitivity reactions to any study drug; Partial cystectomy in the setting of bladder cancer primary tumour or partial nephrectomy; Severe or uncontrolled systemic diseases, history of organ transplant or allogeneic stem cell transplant, or psychological disorders/social situations, and/or substance abuse; History of clinically significant corneal disease; Ongoing toxicities except alopecia from prior cancer treatment must be Grade ≤ 1 or at baseline. Stable Grade 2 toxicities are allowed if unchanged for ≥3 months and managed by standard care; Active or uncontrolled hepatitis B or C virus infection; Known HIV infection that is not well controlled; Any tumour with predominant or pure high grade neuroendocrine carcinoma component; Has clinically severe pulmonary function compromise; Mean resting corrected QTcF > 470 ms regardless of gender, obtained from triplicate 12-lead ECGs performed at screening; Not eligible to receive at least one of SoC according to local regulations/approvals; Currently pregnant (confirmed with positive pregnancy test), breastfeeding or planning to become pregnant.

EU CTIS 2025-525030-57-00