An Open-label Study to Investigate the Efficacy and Safety of Dato-DXd + Rilvegostomig vs SoC in Adult Participants With High-risk MIUC

NCT07720284
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Phase
Phase 3
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Recruitment status
Recruiting
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Participants
915
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Lead sponsor
AstraZeneca
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Start date
2026-07-16
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Number of sites
160
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Summary
Purpose: to assess efficacy and safety of Dato-DXd + rilvegostomig as adjuvant therapy versus SoC in MIUC participants with high-risk residual disease after radical resection. Study details: Duration: \~78 months (6.5 years) from FSI to last subject visit Treatment length: up to \~12 months, depending on randomized arm Visit frequency: every 3 weeks in Arms 1 and 2; every 2-4 weeks per SoC in Arm 3
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Acronym
TU-04
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Short title
An Open-label Study to Investigate the Efficacy and Safety of Dato-DXd + Rilvegostomig vs SoC in Adult Participants With High-risk MIUC
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Official title
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
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Control arm
Active comparator
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 3
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Study type
Interventional
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Completion date
2032-11-23
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First posted
2026-07-22
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Registry last updated
2026-07-22
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Primary completion date
2030-09-11
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Start date
2026-07-16
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Participants
915
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Participant count basis
Estimated
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Planned participants
915
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Protocol amendments
0
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Number of sites
160
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
AstraZeneca
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Source registry
ClinicalTrials.gov
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Registry ID
NCT07720284
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ClinicalTrials.gov ID
NCT07720284
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Single masking
Masking description
sponsor-blind open-label
Masked roles
Outcome assessors
Sources for study design
clinicaltrials.gov

  1. To demonstrate the superiority of Dato-DXd + rilvegostomig (Arm 1) relative to SoC (Arm 3) by assessment of disease-free survival (DFS) (based on Investigator assessments).

    Timeframe: From randomisation until disease recurrence as assessed by investigator or death due to any cause (anticipated to be up to 49 months after the first subject in).

    DFS is defined as the time from randomisation until disease recurrence (local urothelial tract, local non urothelial tract or distant) per RECIST 1.1 as assessed by Investigator, or death due to any cause. The analysis will include all randomised participants as randomised. All events will be included, regardless of whether the participant discontinues study treatment or receives another anti-cancer therapy. The measure of interest is the HR of DFS.

  1. To demonstrate the superiority of Dato-DXd + rilvegostomig (Arm 1) relative to SoC (Arm 3) by assessment of OS (Overall survival).

    Timeframe: OS is defined as the time from randomisation until the date of death due to any cause, up to 78 months from first subject in.

    OS defined as the time from randomisation until the date of death due to any cause. The analysis will include all randomised participants as randomised. All deaths will be included regardless of whether the participant withdraws from therapy or receives another anti-cancer therapy. The measure of interest is the HR of OS.

  2. To demonstrate the superiority of Dato-DXd + rilvegostomig (Arm 1) relative to SoC (Arm 3) by assessment of DFS (based on Blinded Independent Central Review [BICR] assessments).

    Timeframe: From randomisation until disease recurrence as assessed by BICR or death due to any cause (anticipated to be up to 49 months after the first subject in).

    DFS is defined as the time from randomisation until disease recurrence (local urothelial tract, local non urothelial tract or distant) per RECIST 1.1 as assessed by BICR, or death due to any cause. The analysis will include all randomised participants as randomised. All events will be included, regardless of whether the participant discontinues study treatment or receives another anti-cancer therapy. The measure of interest is the HR of DFS.

  3. To estimate the effectiveness of Dato-DXd monotherapy (Arm 2) versus SoC (Arm 3) and effectiveness of Dato-DXd in combination with rilvegostomig (Arm 1) versus Dato-DXd monotherapy (Arm 2) by assessment of OS.

    Timeframe: OS is defined as the time from randomisation until the date of death due to any cause, up to 78 months from first subject in.

    OS defined as the time from randomisation until the date of death due to any cause. The analysis will include all randomised participants as randomised. All deaths will be included regardless of whether the participant withdraws from therapy or receives another anti-cancer therapy. The measure of interest is the HR of OS.

  4. To estimate the effectiveness of Dato-DXd monotherapy (Arm 2) versus SoC (Arm 3) and effectiveness of Dato-DXd in combination with rilvegostomig (Arm 1) versus Dato-DXd monotherapy (Arm 2) by assessment of DFS based on Investigator assessments.

    Timeframe: From randomisation until disease recurrence as assessed by investigator or death due to any cause (anticipated to be up to 49 months after the first subject in).

    DFS is defined as the time from randomisation until disease recurrence (local urothelial tract, local non urothelial tract or distant) per RECIST 1.1 as assessed by Investigator, or death due to any cause. The analysis will include all randomised participants as randomised. All events will be included, regardless of whether the participant discontinues study treatment or receives another anti-cancer therapy. The measure of interest is the HR of DFS.

  5. To estimate the effectiveness of Dato-DXd monotherapy (Arm 2) versus SoC (Arm 3) and effectiveness of Dato-DXd in combination with rilvegostomig (Arm 1) versus Dato-DXd monotherapy (Arm 2) by assessment of DFS by BICR.

    Timeframe: From randomisation until disease recurrence as assessed by BICR or death due to any cause (anticipated to be up to 49 months after the first subject in).

    DFS is defined as the time from randomisation until disease recurrence (local urothelial tract, local non urothelial tract or distant) per RECIST 1.1 as assessed by BICR, or death due to any cause. The analysis will include all randomised participants as randomised. All events will be included, regardless of whether the participant discontinues study treatment or receives another anti-cancer therapy. The measure of interest is the HR of DFS.

  6. To demonstrate effectiveness of Dato-DXd + rilvegostomig (Arm 1) vs SoC (Arm 3) by evaluating DSS (Disease specific survival), NUTRFS (Non-urothelial tract recurrence-free survival), DMFS (Distant metastasis free survival).

    Timeframe: From randomisation up to 49 months after the first subject in.

    DSS is defined as time from randomisation until death due to disease (urothelial cancer). The analysis will include all randomised participants as randomised. The measure of interest is the HR of DSS. NUTRFS is defined as time from randomisation until first local non-urothelial tract or distant recurrence or death due to any cause. The analysis will include all randomised participants as randomised. The measure of interest is the HR of NUTRFS. DMFS is defined as time from randomisation until first distant recurrence (non-local) or death due to any cause The analysis will include all randomised participants as randomised. The measure of interest is the HR of DMFS.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  1. Participant must be > 18 years of age at the time of signing the ICF.

  2. Histologically confirmed MIUC of the bladder or upper tract.

  3. Completed R0 radical resection 28 to 120 days before randomisation, with negative margins and no residual or metastatic disease.

  4. Pathologic evidence of urothelial carcinoma at high-risk of recurrence and

    1. not received neoadjuvant therapy and has pT3-pT4aN0, or any pT with pN+ stage
    2. completed neoadjuvant treatment and has ypT2-ypT4a, or any ypT with ypN+ stage

  5. No evidence of disease at screening,

  6. ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to randomisation.

  7. Minimum life expectancy of > 12 weeks at time of screening.

  8. An archival surgical tumour sample must be available pre-randomisation for central testing.

  9. Adequate organ and bone marrow function within 28 days before randomisation.

  1. Any tumour with predominant or pure high grade neuroendocrine carcinoma component.
  2. Partial cystectomy in the setting of bladder cancer primary tumour or partial nephrectomy.
  3. Any adjuvant systemic or radiation therapy post-surgery for urothelial carcinoma.
  4. Severe or uncontrolled systemic diseases, history of organ transplant or allogeneic stem cell transplant, or psychological disorders/social situations, and/or substance abuse.
  5. History of clinically significant corneal disease.
  6. 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.
  7. 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.
  8. Active or uncontrolled hepatitis B or C virus infection.
  9. Known HIV infection that is not well controlled.
  10. Any other active or uncontrolled infection including tuberculosis requiring systemic treatment that has not resolved by the time of randomisation.
  11. 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.
  12. Has clinically severe pulmonary function compromise.
  13. Mean resting corrected QTcF > 470 ms regardless of gender, obtained from triplicate 12-lead ECGs performed at screening
  14. Uncontrolled or significant cardiac conditions.
  15. Active or prior documented autoimmune or inflammatory disorders requiring systemic treatment in the past 5 years.
  16. Prior exposure to TROP2-directed therapies, other ADCs with deruxtecan, therapeutic anti-cancer vaccines, anti-TIGIT therapy or any other anti-cancer therapy targeting immune-regulatory receptors or mechanisms.
  17. Current or prior use of immunosuppressive medication within 14 days prior to treatment assignment/randomisation.
  18. Known history of severe hypersensitivity reactions to any study drug
  19. Not eligible to receive at least one of SoC according to local regulations/approvals.
  20. Currently pregnant (confirmed with positive pregnancy test), breastfeeding or planning to become pregnant.
Sources for eligibility
clinicaltrials.gov

  • Research SiteHot Springs, United StatesNot yet recruiting
  • Research SiteLittle Rock, United StatesNot yet recruiting
  • Research SiteLittle Rock, United StatesNot yet recruiting
  • Research SiteSan Francisco, United StatesNot yet recruiting
  • Research SiteChicago, United StatesWithdrawn
  • Research SiteBoston, United StatesNot yet recruiting
  • Research SiteKansas City, United StatesNot yet recruiting
  • Research SiteLincoln, United StatesNot yet recruiting
  • Research SiteOmaha, United StatesNot yet recruiting
  • Research SiteAlbany, United StatesNot yet recruiting
  • Research SiteNew York, United StatesNot yet recruiting
  • Research SiteCleveland, United StatesNot yet recruiting
  • Research SiteMyrtle Beach, United StatesNot yet recruiting
  • Research SiteNashville, United StatesNot yet recruiting
  • Research SiteDallas, United StatesNot yet recruiting
  • Research SiteFalls Church, United StatesNot yet recruiting
  • Research SiteSeattle, United StatesNot yet recruiting
  • Research SiteTacoma, United StatesNot yet recruiting
  • Research SiteMilwaukee, United StatesNot yet recruiting
  • Research SiteAuchenflower, AustraliaWithdrawn
  • Research SiteBallarat, AustraliaNot yet recruiting
  • Research SiteClayton, AustraliaNot yet recruiting
  • Research SiteDarlinghurst, AustraliaNot yet recruiting
  • Research SiteElizabeth Vale, AustraliaNot yet recruiting
  • Research SiteSouth Brisbane, AustraliaNot yet recruiting

And 135 more, listed on the interactive page.

Sources for sites
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Related records

Drugs (6)

Collaborators (1)

Lead sponsors (1)

Conditions (3)

Targets (20)