NCT07720284 · AstraZeneca
An Open-label Study to Investigate the Efficacy and Safety of Dato-DXd + Rilvegostomig vs SoC in Adult Participants With High-risk MIUC
(TU-04)
What this study is about
Purpose: to assess effectiveness 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.
View original scientific description
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.
Interventions
DRUG
Dato-DXd
Dato-DXd is an ADC comprised of a recombinant humanised anti-TROP2 IgG1 mAb, MAAP-9001a, which is covalently conjugated via a cleavable drug-linker, MAAA1162a (the complex of MAAA-1181a and a maleimide tetrapeptide linker), using thioether bonds to the topoisomerase I inhibitor DXd.
DRUG
Rilvegostomig
Rilvegostomig is a monovalent, bispecific, humanised, IgG1 mAb engineered with an Fc domain that carries a triple mutation (L234F/L235E/P331S) designed to reduce Fc-mediated effector functions. Rilvegostomig contains 2 distinct paratopes that bind to human TIGIT and PD-1 and inhibit binding to their respective immuno-suppressive ligands.
DRUG
Durvalumab
A fully human monoclonal antibody that blocks the PD-L1 checkpoint to restore anti-tumor T-cell activity. Durvalumab is approved for Muscle invasive bladder cancer (MIBC) as perioperative regime.
DRUG
Nivolumab
A fully human monoclonal antibody against PD-1, promoting anti-tumor immunity. Approved across many malignancies such as melanoma, NSCLC, renal cell carcinoma, Hodgkin lymphoma, hepatocellular carcinoma, and colorectal cancer (dMMR/MSI-H), often alone or with ipilimumab. It's used in several cancers, notably unresectable stage III non-small cell lung cancer after chemoradiation and extensive-stage small cell lung cancer in combination regimens, among others, and is also approved for patients with muscle-invasive urothelial carcinoma (MIUC) at high risk of recurrence in the adjuvant setting.
DRUG
Pembrolizumab
A humanized monoclonal antibody targeting PD-1, enhancing T-cell-mediated immune responses against tumors. Indications span multiple cancers including melanoma, NSCLC, head and neck squamous cell carcinoma, urothelial carcinoma, MSI-H/dMMR tumors, and more.
DRUG
Enfortumab vedotin
An antibody-drug conjugate (ADC) comprised of a fully human anti-Nectin-4 IgG1 monoclonal antibody, linked via a protease-cleavable maleimide-based linker to the microtubule-disrupting agent monomethyl auristatin E (MMAE), which is conjugated through thioether bonds. Upon binding to Nectin-4-expressing cells, the ADC is internalized and releases MMAE, leading to disruption of microtubule dynamics and subsequent tumor cell death. Enfortumab vedotin is approved in urothelial cancers.
Primary outcome measures
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).
Time frame: 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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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
- not received neoadjuvant therapy and has pT3-pT4aN0, or any pT with pN+ stage
- 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 pre-randomisation for central testing.
- Adequate organ and bone marrow function within 28 days before randomisation.
Exclusion criteria
- Any tumour with predominant or pure high grade neuroendocrine carcinoma component.
- Partial cystectomy in the setting of bladder cancer primary tumour or partial nephrectomy.
- Any adjuvant systemic or radiation therapy post-surgery for urothelial carcinoma.
- 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.
- 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.
- 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 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.
- Has clinically severe pulmonary function compromise.
- Mean resting corrected QTcF \> 470 ms regardless of gender, obtained from triplicate 12-lead ECGs performed at screening
- Uncontrolled or significant cardiac conditions.
- 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 immune-regulatory receptors or mechanisms.
- Current or prior use of immunosuppressive medication within 14 days prior to treatment assignment/randomisation.
- Known history of severe hypersensitivity reactions to any study drug
- 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.
Where
- Hot Springs, Arkansas
- Little Rock, Arkansas
- San Francisco, California
- Chicago, Illinois
- Boston, Massachusetts
- Kansas City, Missouri
- Lincoln, Nebraska
- Omaha, Nebraska
- Albany, New York
- New York, New York
- Cleveland, Ohio
- Myrtle Beach, South Carolina
And 6 more locations — see the full list below.
Collaborators
Daiichi Sankyo
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jul 22, 2026 · Source of record for eligibility and locations