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
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
1 other identifier
interventional
915
16 countries
160
Brief 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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jul 2026
Longer than P75 for phase_3
160 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 10, 2026
CompletedStudy Start
First participant enrolled
July 16, 2026
CompletedFirst Posted
Study publicly available on registry
July 22, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 11, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
November 23, 2032
July 22, 2026
July 1, 2026
4.2 years
June 10, 2026
July 17, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (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).
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.
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).
Secondary Outcomes (6)
To demonstrate the superiority of Dato-DXd + rilvegostomig (Arm 1) relative to SoC (Arm 3) by assessment of OS (Overall survival).
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.
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).
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).
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.
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.
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.
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).
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.
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).
- +1 more secondary outcomes
Other Outcomes (4)
To assess the pharmacokinetics (PK) of Dato-DXd and DXd, alone in the Dato-DXd monotherapy arm (Arm 2) and in combination with rilvegostomig (Arm 1). To assess the PK of rilvegostomig in Arm 1.
Day 1 of Cycles 1, 2, 4, 5, and 8 (each cycle is 21 days), at the end of treatment (approximately up to 12 months after randomization), and at the end of safety follow-up (approximately up to 15 months after randomization).
To investigate the immunogenicity of Dato-DXd and rilvegostomig in Dato-DXd + rilvegostomig combination therapy (Arm 1) and Dato-DXd monotherapy (Arm 2).
Day 1 of Cycles 1, 2, 4, 5, 6, 8, 10, and 14 (each cycle is 21 days), at the end of treatment (approximately up to 12 months after randomization), and at the end of safety follow-up (approximately up to 15 months after randomization).
To assess participant-reported global health status (GHS)/quality of life (QoL) in participants treated with Dato-DXd + rilvegostomig (Arm 1) as compared with SoC (Arm 3).
D1C1, then every 3w (21d cycles) until end of treatment (~12m from randomization); thereafter every 6w after treatment discontinuation until recurrence, start of subsequent therapy, or study discontinuation, up to 18m post-treatment.
- +1 more other outcomes
Study Arms (3)
Arm 1: Dato-DXd + rilvegostomig
EXPERIMENTALDato-DXd: 6 mg/kg IV Q3W for 9 cycles (approximately 6 months), can be extended based on Investigator assessment of tolerability up to 17 cycles or up to 1 year + rilvegostomig: 750 mg IV Q3W 17 cycles or up to 1 year whichever occurs first.
Arm 2: Dato-DXd monotherapy
EXPERIMENTALDato-DXd: 6 mg/kg IV Q3W for 9 cycles (approximately 6 months), can be extended based on Investigator assessment of tolerability up to 17 cycles or up to 1 year.
Arm 3 (SoC): nivolumab or durvalumab or EV + pembrolizumab
ACTIVE COMPARATOREither: Nivolumab: 240 mg IV Q2W OR 480 mg IV Q4W up to 1 year Or: Durvalumab: 1500 mg IV Q4W for 8 cycles (or at a dose of 20 mg/kg Q4W in participants who weigh ≤ 30 kg) Or: EV 1.25 mg/kg D1, D8 Q3W up to 6 cycles + pembrolizumab 200 mg IV Q3W up to 14 cycles or 400 mg IV Q6W up to 7 cycles.
Interventions
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.
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.
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.
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.
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.
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.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
- Daiichi Sankyocollaborator
Study Sites (160)
Research Site
Hot Springs, Arkansas, 71913, United States
Research Site
Little Rock, Arkansas, 72205, United States
Research Site
Little Rock, Arkansas, 72211, United States
Research Site
San Francisco, California, 94143, United States
Research Site
Chicago, Illinois, 60637, United States
Research Site
Boston, Massachusetts, 02215, United States
Research Site
Kansas City, Missouri, 64132, United States
Research Site
Lincoln, Nebraska, 68506, United States
Research Site
Omaha, Nebraska, 68130, United States
Research Site
Albany, New York, 12208, United States
Research Site
New York, New York, 10065, United States
Research Site
Cleveland, Ohio, 44195, United States
Research Site
Myrtle Beach, South Carolina, 29572, United States
Research Site
Nashville, Tennessee, 37203, United States
Research Site
Dallas, Texas, 75235, United States
Research Site
Falls Church, Virginia, 22042, United States
Research Site
Seattle, Washington, 98109, United States
Research Site
Tacoma, Washington, 98405, United States
Research Site
Milwaukee, Wisconsin, 53226, United States
Research Site
Auchenflower, 4066, Australia
Research Site
Ballarat, 3350, Australia
Research Site
Clayton, 3168, Australia
Research Site
Darlinghurst, 2010, Australia
Research Site
Elizabeth Vale, 5112, Australia
Research Site
South Brisbane, 4101, Australia
Research Site
St Albans, 3021, Australia
Research Site
Barretos, 14784-400, Brazil
Research Site
Curitiba, 81520-060, Brazil
Research Site
Salvador, 41950-640, Brazil
Research Site
São Paulo, 01323-903, Brazil
Research Site
São Paulo, 05652-900, Brazil
Research Site
Calgary, Alberta, T2N 5G2, Canada
Research Site
Abbotsford British Columbia, British Columbia, V2S0C2, Canada
Research Site
Barrie, Ontario, L4M 6M2, Canada
Research Site
Hamilton, Ontario, L8V 5C2, Canada
Research Site
Kingston, Ontario, K7L 2V7, Canada
Research Site
London, Ontario, N6C 2R5, Canada
Research Site
Mississauga, Ontario, L5M 2N1, Canada
Research Site
Montreal, Quebec, H2X 0A9, Canada
Research Site
Montreal, Quebec, H3A 1A1, Canada
Research Site
Beijing, 100034, China
Research Site
Beijing, 100050, China
Research Site
Beijing, 100191, China
Research Site
Changsha, 410013, China
Research Site
Chengdu, 610000, China
Research Site
Chengdu, 610072, China
Research Site
Chongqing, 400016, China
Research Site
Chongqing, 400030, China
Research Site
Fuzhou, 350005, China
Research Site
Guangzhou, 510220, China
Research Site
Guangzhou, 510288, China
Research Site
Guiyang, 550044, China
Research Site
Hangzhou, 310003, China
Research Site
Hangzhou, 310009, China
Research Site
Harbin, 150049, China
Research Site
Jinan, 250012, China
Research Site
Jinan, 250021, China
Research Site
Kunming, 650101, China
Research Site
Kunming, 650118, China
Research Site
Lanzhou, 730030, China
Research Site
Nanchang, 330006, China
Research Site
Nanjing, 210008, China
Research Site
Nanning, 530021, China
Research Site
Ningbo, 315010, China
Research Site
Qingdao, 266003, China
Research Site
Shanghai, 200040, China
Research Site
Shenyang, 110004, China
Research Site
Shenyang, 110042, China
Research Site
Suining Shi, 629000, China
Research Site
Tianjin, 300211, China
Research Site
Wenzhou, 325000, China
Research Site
Wuhan, 430022, China
Research Site
Wuhan, 430030, China
Research Site
Xuzhou, 221000, China
Research Site
Zhengzhou, 450008, China
Research Site
Bordeaux, 33000, France
Research Site
Montpellier, 34298, France
Research Site
Paris, 75014, France
Research Site
Pierre-Bénite, 69310, France
Research Site
Poitiers, 86000, France
Research Site
Strasbourg, 67098, France
Research Site
Bochum, 44791, Germany
Research Site
Bonn, 53127, Germany
Research Site
Dresden, 01307, Germany
Research Site
Duisburg, 47169, Germany
Research Site
Frankfurt am Main, 60431, Germany
Research Site
Hamburg, 20246, Germany
Research Site
Hanover, 30625, Germany
Research Site
Herne, 44625, Germany
Research Site
Magdeburg, 39120, Germany
Research Site
Mannheim, 68167, Germany
Research Site
Marburg, 35043, Germany
Research Site
Mettmann, 40822, Germany
Research Site
Münster, 48149, Germany
Research Site
Nuremberg, 90419, Germany
Research Site
Nürtingen, 72622, Germany
Research Site
Regensburg, 93053, Germany
Research Site
Rostock, 18057, Germany
Research Site
Stuttgart, 70174, Germany
Research Site
Tübingen, 72076, Germany
Research Site
Ulm, 89081, Germany
Research Site
Kolkata, 700160, India
Research Site
Kottayam, 686008, India
Research Site
Nashik, 422011, India
Research Site
Navi Mumbai, 410210, India
Research Site
New Delhi, 110076, India
Research Site
New Delhi, 110085, India
Research Site
New Delhi, 11029, India
Research Site
Bari, 70120, Italy
Research Site
Florence, 50134, Italy
Research Site
Padova, 35128, Italy
Research Site
Roma, 00168, Italy
Research Site
Rozzano, 20089, Italy
Research Site
Tricase, 73039, Italy
Research Site
Fukuoka, 811-1347, Japan
Research Site
Fukuoka, 812-8582, Japan
Research Site
Hamamatsu, 431-3192, Japan
Research Site
Hirosaki-shi, 036-8563, Japan
Research Site
Kanazawa, 920-8641, Japan
Research Site
Kashihara-shi, 634-8522, Japan
Research Site
Kawasaki-shi, 216-8511, Japan
Research Site
Kita-gun, 761-0793, Japan
Research Site
Kobe, 650-0017, Japan
Research Site
Kōtoku, 135-8550, Japan
Research Site
Kumamoto, 860-0008, Japan
Research Site
Nagasaki, 852-8501, Japan
Research Site
Nagoya, 466-8560, Japan
Research Site
Osaka, 541-8567, Japan
Research Site
Osaka, 545-8586, Japan
Research Site
Toyama, 930-0194, Japan
Research Site
Tsukuba, 305-8576, Japan
Research Site
Gdansk, 80-952, Poland
Research Site
Koszalin, 75-581, Poland
Research Site
Poznan, 61-731, Poland
Research Site
Siedlce, 08-110, Poland
Research Site
Skórzewo, 60-185, Poland
Research Site
Wroclaw, 50-556, Poland
Research Site
Wroclaw, 53-413, Poland
Research Site
Seoul, 03080, South Korea
Research Site
Seoul, 06591, South Korea
Research Site
Seoul, 3722, South Korea
Research Site
Seoul, 5505, South Korea
Research Site
Seoul, 6351, South Korea
Research Site
L'Hospitalet de Llobregat, 08908, Spain
Research Site
Las Palmas de Gran Canaria, 35016, Spain
Research Site
Madrid, 28040, Spain
Research Site
Santander, 39008, Spain
Research Site
Seville, 41013, Spain
Research Site
Kaohsiung City, 80756, Taiwan
Research Site
Kaohsiung City, 813, Taiwan
Research Site
Kaohsiung City, 83301, Taiwan
Research Site
Tainan, 704, Taiwan
Research Site
Taipei, 11217, Taiwan
Research Site
Taoyuan, 333, Taiwan
Research Site
Bangkok, 10700, Thailand
Research Site
Hat Yai, 90110, Thailand
Research Site
Bristol, BS2 8ED, United Kingdom
Research Site
Cambridge, CB2 0QQ, United Kingdom
Research Site
Preston, PR2 9HT, United Kingdom
Research Site
Sheffield, S10 2SJ, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
AstraZeneca Clinical Study Information Center
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Masking Details
- sponsor-blind open-label
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 10, 2026
First Posted
July 22, 2026
Study Start
July 16, 2026
Primary Completion (Estimated)
September 11, 2030
Study Completion (Estimated)
November 23, 2032
Last Updated
July 22, 2026
Record last verified: 2026-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- ICF
- Time Frame
- Study start to completion date
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.