High-risk Muscle Invasive Urothelial CarcinomaPhase 3TU-04NCT07720284

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

A Phase 3 study testing Dato-DXd, Rilvegostomig and Durvalumab in people with High-risk Muscle Invasive Urothelial Carcinoma, run by AstraZeneca at 160 sites in 16 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: High-risk Muscle Invasive Urothelial Carcinoma
What is being tested?: Dato-DXd, Rilvegostomig and Durvalumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 915 participants
Where: 160 sitesin 16 countries
Study dates: 16 Jul 2026to 23 Nov 2032
Phase: Phase 3
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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.

Who cannot join

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.

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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.

Trial locations and contacts

160 sites in 16 countries. Contact the study team or a site near you to ask about taking part.

AstraZeneca Clinical Study Information Center contact

1-877-240-9479

information.center@astrazeneca.com

Country

City, postcode or hospital

Sites recruiting now only

160 sites in 16 countries

China35 sites, 35 recruiting

Research Site
Beijing, 100034
Not yet recruiting
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Beijing, 100050
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Beijing, 100191
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Changsha, 410013
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Chengdu, 610000
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Chengdu, 610072
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Chongqing, 400016
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Chongqing, 400030
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Fuzhou, 350005
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Guangzhou, 510220
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Guangzhou, 510288
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Guiyang, 550044
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Hangzhou, 310003
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Hangzhou, 310009
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Harbin, 150049
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Jinan, 250012
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Jinan, 250021
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Kunming, 650101
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Kunming, 650118
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Lanzhou, 730030
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Nanchang, 330006
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Nanjing, 210008
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Nanning, 530021
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Ningbo, 315010
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Qingdao, 266003
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Shanghai, 200040
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Shenyang, 110004
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Shenyang, 110042
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Suining Shi, 629000
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Tianjin, 300211
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Wenzhou, 325000
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Wuhan, 430022
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Wuhan, 430030
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Xuzhou, 221000
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Zhengzhou, 450008
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Other trials in China

Germany20 sites, 20 recruiting

Research Site
Bochum, 44791
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Bonn, 53127
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Dresden, 01307
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Duisburg, 47169
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Frankfurt am Main, 60431
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Hamburg, 20246
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Hanover, 30625
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Herne, 44625
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Magdeburg, 39120
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Mannheim, 68167
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Marburg, 35043
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Mettmann, 40822
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Münster, 48149
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Nuremberg, 90419
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Nürtingen, 72622
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Regensburg, 93053
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Rostock, 18057
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Stuttgart, 70174
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Tübingen, 72076
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Ulm, 89081
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Other trials in Germany

United States19 sites, 18 recruiting

Research Site
Albany, New York, 12208
Not yet recruiting
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Boston, Massachusetts, 02215
Not yet recruiting
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Chicago, Illinois, 60637
Withdrawn
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Cleveland, Ohio, 44195
Not yet recruiting
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Dallas, Texas, 75235
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Falls Church, Virginia, 22042
Not yet recruiting
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Hot Springs, Arkansas, 71913
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Kansas City, Missouri, 64132
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Lincoln, Nebraska, 68506
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Little Rock, Arkansas, 72205
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Little Rock, Arkansas, 72211
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Milwaukee, Wisconsin, 53226
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Myrtle Beach, South Carolina, 29572
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Nashville, Tennessee, 37203
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New York, New York, 10065
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Omaha, Nebraska, 68130
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San Francisco, California, 94143
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Seattle, Washington, 98109
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Tacoma, Washington, 98405
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Other trials in United States

Japan17 sites, 15 recruiting

Research Site
Fukuoka, 811-1347
Not yet recruiting
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Fukuoka, 812-8582
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Hamamatsu, 431-3192
Not yet recruiting
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Hirosaki-shi, 036-8563
Withdrawn
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Kanazawa, 920-8641
Not yet recruiting
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Kashihara-shi, 634-8522
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Kawasaki-shi, 216-8511
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Kita-gun, 761-0793
Withdrawn
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Kobe, 650-0017
Not yet recruiting
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Kōtoku, 135-8550
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Kumamoto, 860-0008
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Nagasaki, 852-8501
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Nagoya, 466-8560
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Osaka, 541-8567
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Osaka, 545-8586
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Toyama, 930-0194
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Tsukuba, 305-8576
Not yet recruiting

Other trials in Japan

Canada9 sites, 9 recruiting

Research Site
Abbotsford British Columbia, British Columbia, V2S0C2
Not yet recruiting
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Barrie, Ontario, L4M 6M2
Recruiting
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Calgary, Alberta, T2N 5G2
Not yet recruiting
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Hamilton, Ontario, L8V 5C2
Recruiting
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Kingston, Ontario, K7L 2V7
Not yet recruiting
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London, Ontario, N6C 2R5
Not yet recruiting
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Mississauga, Ontario, L5M 2N1
Not yet recruiting
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Montreal, Quebec, H2X 0A9
Not yet recruiting
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Montreal, Quebec, H3A 1A1
Not yet recruiting

Other trials in Canada

Australia7 sites, 5 recruiting

Research Site
Auchenflower, 4066
Withdrawn
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Ballarat, 3350
Not yet recruiting
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Clayton, 3168
Not yet recruiting
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Darlinghurst, 2010
Not yet recruiting
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Elizabeth Vale, 5112
Not yet recruiting
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South Brisbane, 4101
Not yet recruiting
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St Albans, 3021
Withdrawn

Other trials in Australia

India7 sites, 7 recruiting

Research Site
Kolkata, 700160
Not yet recruiting
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Kottayam, 686008
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Nashik, 422011
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Navi Mumbai, 410210
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New Delhi, 110076
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New Delhi, 110085
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New Delhi, 11029
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Other trials in India

Poland7 sites, 7 recruiting

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Gdansk, 80-952
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Koszalin, 75-581
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Poznan, 61-731
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Siedlce, 08-110
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Skórzewo, 60-185
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Wroclaw, 50-556
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Wroclaw, 53-413
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Other trials in Poland

France6 sites, 6 recruiting

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Bordeaux, 33000
Not yet recruiting
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Montpellier, 34298
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Paris, 75014
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Pierre-Bénite, 69310
Not yet recruiting
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Poitiers, 86000
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Strasbourg, 67098
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Other trials in France

Italy6 sites, 6 recruiting

Research Site
Bari, 70120
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Florence, 50134
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Padova, 35128
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Roma, 00168
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Rozzano, 20089
Not yet recruiting
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Tricase, 73039
Not yet recruiting

Other trials in Italy

Taiwan6 sites, 6 recruiting

Research Site
Kaohsiung City, 80756
Recruiting
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Kaohsiung City, 813
Not yet recruiting
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Kaohsiung City, 83301
Not yet recruiting
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Tainan, 704
Not yet recruiting
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Taipei, 11217
Not yet recruiting
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Taoyuan, 333
Not yet recruiting

Other trials in Taiwan

Brazil5 sites, 5 recruiting

Research Site
Barretos, 14784-400
Not yet recruiting
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Curitiba, 81520-060
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Salvador, 41950-640
Not yet recruiting
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São Paulo, 01323-903
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São Paulo, 05652-900
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Other trials in Brazil

South Korea5 sites, 5 recruiting

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Seoul, 03080
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Seoul, 06591
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Seoul, 3722
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Seoul, 5505
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Seoul, 6351
Not yet recruiting

Other trials in South Korea

Spain5 sites, 5 recruiting

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L'Hospitalet de Llobregat, 08908
Not yet recruiting
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Las Palmas de Gran Canaria, 35016
Not yet recruiting
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Madrid, 28040
Not yet recruiting
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Santander, 39008
Not yet recruiting
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Seville, 41013
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Other trials in Spain

United Kingdom4 sites, 4 recruiting

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Bristol, BS2 8ED
Not yet recruiting
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Cambridge, CB2 0QQ
Not yet recruiting
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Preston, PR2 9HT
Not yet recruiting
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Sheffield, S10 2SJ
Not yet recruiting

Other trials in United Kingdom

Thailand2 sites, 2 recruiting

Research Site
Bangkok, 10700
Not yet recruiting
Research Site
Hat Yai, 90110
Not yet recruiting

Other trials in Thailand

About this study

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

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

Conditions: High-risk Muscle Invasive Urothelial Carcinoma
Being tested: Dato-DXd, Rilvegostomig, Durvalumab, Nivolumab, Pembrolizumab
Keywords: Urothelial Carcinoma, Carcinoma, Datopotamab deruxtecan, Dato-DXd, DS-1062a, Rilvegostomig, AZD2936, Invasive Urothelial Carcinoma, Muscle Invasive Urothelial Carcinoma, High-risk MIUC, Adjuvant Urothelial Cancer, Bladder cancer, UTUC, Trop2. directed ADC, Immunotherapy, phase III
Medical subject headings: Carcinoma, Transitional Cell, Carcinoma, Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Dato-DXdDrug
Also called Datopotamab deruxtecan, (Dato-DXd, DS-1062a)
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.
RilvegostomigDrug
Also called AZD2936
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.
DurvalumabDrug
Also called Imfinzi, MEDI4736
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.
NivolumabDrug
Also called OPDIVO®, BMS-936558
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.
PembrolizumabDrug
Also called Keytruda, MK-3475
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.
Enfortumab vedotinDrug
Also called Padcev®, ASG-22CE, AGS-22M6E
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.

Study groups in NCT07720284
Study group	Role	What they receive
Arm 1: Dato-DXd + rilvegostomig	Experimental	Dato-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. Receives: Drug: Dato-DXd; Drug: Rilvegostomig
Arm 2: Dato-DXd monotherapy	Experimental	Dato-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. Receives: Drug: Dato-DXd
Arm 3 (SoC): nivolumab or durvalumab or EV + pembrolizumab	Active comparator	Either: 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. Receives: Drug: Durvalumab; Drug: Nivolumab; Drug: Pembrolizumab; Drug: Enfortumab vedotin

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Jul 202623 Nov 2032

First posted22 Jul 2026
Study start16 Jul 2026
Primary completion11 Sep 2030 (estimated)
Study completion23 Nov 2032 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for High-risk Muscle Invasive Urothelial CarcinomaStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind
Who is masked: Outcomes assessor
Enrolment: 915 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07720284
Sponsor's protocol ID: D763TC00001
Acronym: TU-04
Status last verified: Jul 2026
First submitted: 10 Jun 2026
Last updated: 22 Jul 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: 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.

Interested in taking part?

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

Active, not recruitingPhase 2
A Study to Evaluate the Efficacy and Safety of Autogene Cevumeran With Nivolumab Versus Nivolumab Alone in Participants With High-risk Muscle-invasive Urothelial Carcinoma (MIUC)
Muscle-invasive Urothelial Carcinoma
RecruitingPhase 2
Testing the Addition of the Immunotherapy Drug, Pembrolizumab, to Radiation Therapy Compared to the Usual Chemotherapy Treatment During Radiation Therapy for Bladder Cancer, PARRC Trial
Non-Muscle Invasive Bladder Urothelial Carcinoma, Recurrent Non-Muscle Invasive Bladder Urothelial Carcinoma
RecruitingPhase 2
Is Prolonged Systemic Immunotherapy Necessary After Achieving Tumor-free Status in Patients With Extensive Transurethrally Unresectable Very-high-risk NMIBC?
Bladder (Urothelial, Transitional Cell) Cancer, Non Muscle Invasive Bladder Cancer
RecruitingPhase 3
Efficacy and Safety of Intravesical TARA-002 Compared With Investigator's Choice of Intravesical Chemotherapy in Participants With BCG-naïve High-grade Non-muscle Invasive Bladder Cancer
Bladder (Urothelial, Transitional Cell) Cancer, Non-Muscle Invasive Bladder Carcinoma
Active, not recruitingEarly Phase 1
Durvalumab and Tremelimumab in Treating Patients With Muscle-Invasive, High-Risk Urothelial Cancer That Cannot Be Treated With Cisplatin-Based Therapy Before Surgery
Hydronephrosis, Infiltrating Bladder Urothelial Carcinoma Sarcomatoid Variant

All High-risk Muscle Invasive Urothelial Carcinoma trials

Study at a glance

From the registry record, last updated by the sponsor on 22 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT07720284
Acronym / sponsor ID: TU-04 / D763TC00001
Conditions: High-risk Muscle Invasive Urothelial Carcinoma
Keywords: Urothelial Carcinoma, Carcinoma, Datopotamab deruxtecan, Dato-DXd, DS-1062a, Rilvegostomig, AZD2936, Invasive Urothelial Carcinoma
Phase: Phase 3
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 915 participants (estimated)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Daiichi Sankyo
Study start: 16 Jul 2026 (actual)
Primary completion: 11 Sep 2030 (estimated)
Study completion: 23 Nov 2032 (estimated)
First posted: 22 Jul 2026 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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:

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Arm 1: Dato-DXd + rilvegostomig	Experimental	Drug: Dato-DXd, Drug: RilvegostomigDato-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	Experimental	Drug: Dato-DXdDato-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 comparator	Drug: Durvalumab, Drug: Nivolumab, Drug: Pembrolizumab, Drug: Enfortumab vedotinEither: 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

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
No evidence of disease at screening,

Key exclusion criteria (20 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Dato-DXdAlso: Datopotamab deruxtecan, (Dato-DXd, DS-1062a)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	Arm 1: Dato-DXd + rilvegostomig, Arm 2: Dato-DXd monotherapy
RilvegostomigAlso: AZD2936Rilvegostomig 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	Arm 1: Dato-DXd + rilvegostomig
DurvalumabAlso: Imfinzi, MEDI4736A 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	Arm 3 (SoC): nivolumab or durvalumab or EV + pembrolizumab
NivolumabAlso: OPDIVO®, BMS-936558A 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	Arm 3 (SoC): nivolumab or durvalumab or EV + pembrolizumab
PembrolizumabAlso: Keytruda, MK-3475A 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	Arm 3 (SoC): nivolumab or durvalumab or EV + pembrolizumab
Enfortumab vedotinAlso: Padcev®, ASG-22CE, AGS-22M6EAn 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.	Drug	Arm 3 (SoC): nivolumab or durvalumab or EV + pembrolizumab

Primary outcome

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.

6 secondary outcomes

To demonstrate the superiority of Dato-DXd + rilvegostomig (Arm 1) relative to SoC (Arm 3) by assessment of OS (Overall survival).
Time frame: 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).
Time frame: 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.
Time frame: 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.
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).
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.
Time frame: 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 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).
Time frame: From randomisation up to 49 months after the first subject in.

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2026.
Individual participant dataSharing planned: Yes. 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

AstraZeneca Clinical Study Information Center contact

1-877-240-9479

information.center@astrazeneca.com

160 sites in 16 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Dato-DXd, Rilvegostomig and Durvalumab in people with High-risk Muscle Invasive Urothelial Carcinoma, run by AstraZeneca at 160 sites in 16 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 22 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 160 sites in China, Germany, United States, Japan, Canada and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact AstraZeneca Clinical Study Information Center (1-877-240-9479, information.center@astrazeneca.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07720284.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2026.