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)

July 17, 2026 updated by: AstraZeneca

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
915

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Australia
      • Auchenflower, Australia, 4066
        • Withdrawn
        • Research Site
      • Ballarat, Australia, 3350
        • Not yet recruiting
        • Research Site
      • Clayton, Australia, 3168
        • Not yet recruiting
        • Research Site
      • Darlinghurst, Australia, 2010
        • Not yet recruiting
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      • Elizabeth Vale, Australia, 5112
        • Not yet recruiting
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      • South Brisbane, Australia, 4101
        • Not yet recruiting
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      • St Albans, Australia, 3021
        • Withdrawn
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  • Brazil
      • Barretos, Brazil, 14784-400
        • Not yet recruiting
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      • Curitiba, Brazil, 81520-060
        • Not yet recruiting
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      • Salvador, Brazil, 41950-640
        • Not yet recruiting
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      • São Paulo, Brazil, 05652-900
        • Not yet recruiting
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      • São Paulo, Brazil, 01323-903
        • Not yet recruiting
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  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 5G2
        • Not yet recruiting
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    • British Columbia
      • Abbotsford British Columbia, British Columbia, Canada, V2S0C2
        • Not yet recruiting
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    • Ontario
      • Barrie, Ontario, Canada, L4M 6M2
        • Recruiting
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      • Hamilton, Ontario, Canada, L8V 5C2
        • Recruiting
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      • Kingston, Ontario, Canada, K7L 2V7
        • Not yet recruiting
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      • London, Ontario, Canada, N6C 2R5
        • Not yet recruiting
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      • Mississauga, Ontario, Canada, L5M 2N1
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    • Quebec
      • Montreal, Quebec, Canada, H2X 0A9
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      • Montreal, Quebec, Canada, H3A 1A1
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  • China
      • Beijing, China, 100050
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      • Beijing, China, 100191
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      • Beijing, China, 100034
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      • Changsha, China, 410013
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      • Chengdu, China, 610072
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      • Chengdu, China, 610000
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      • Chongqing, China, 400030
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      • Chongqing, China, 400016
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      • Fuzhou, China, 350005
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      • Guangzhou, China, 510220
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      • Guangzhou, China, 510288
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      • Guiyang, China, 550044
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      • Hangzhou, China, 310003
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      • Hangzhou, China, 310009
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      • Harbin, China, 150049
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      • Jinan, China, 250012
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      • Jinan, China, 250021
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      • Kunming, China, 650101
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      • Kunming, China, 650118
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      • Lanzhou, China, 730030
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      • Nanchang, China, 330006
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      • Nanjing, China, 210008
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      • Nanning, China, 530021
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      • Ningbo, China, 315010
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      • Qingdao, China, 266003
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      • Shanghai, China, 200040
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      • Shenyang, China, 110042
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      • Shenyang, China, 110004
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      • Suining Shi, China, 629000
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      • Tianjin, China, 300211
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      • Wenzhou, China, 325000
        • Not yet recruiting
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      • Wuhan, China, 430022
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      • Wuhan, China, 430030
        • Not yet recruiting
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      • Xuzhou, China, 221000
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      • Zhengzhou, China, 450008
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  • France
      • Bordeaux, France, 33000
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      • Montpellier, France, 34298
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      • Paris, France, 75014
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      • Pierre-Bénite, France, 69310
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      • Poitiers, France, 86000
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      • Strasbourg, France, 67098
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  • Germany
      • Bochum, Germany, 44791
        • Not yet recruiting
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      • Bonn, Germany, 53127
        • Not yet recruiting
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      • Dresden, Germany, 01307
        • Not yet recruiting
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      • Duisburg, Germany, 47169
        • Not yet recruiting
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      • Frankfurt am Main, Germany, 60431
        • Not yet recruiting
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      • Hamburg, Germany, 20246
        • Not yet recruiting
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      • Hanover, Germany, 30625
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      • Herne, Germany, 44625
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      • Magdeburg, Germany, 39120
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      • Mannheim, Germany, 68167
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      • Marburg, Germany, 35043
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      • Mettmann, Germany, 40822
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      • Münster, Germany, 48149
        • Not yet recruiting
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      • Nuremberg, Germany, 90419
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      • Nürtingen, Germany, 72622
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      • Regensburg, Germany, 93053
        • Not yet recruiting
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      • Rostock, Germany, 18057
        • Not yet recruiting
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      • Stuttgart, Germany, 70174
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      • Tübingen, Germany, 72076
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      • Ulm, Germany, 89081
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  • India
      • Kolkata, India, 700160
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      • Kottayam, India, 686008
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      • Nashik, India, 422011
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      • Navi Mumbai, India, 410210
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      • New Delhi, India, 110085
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      • New Delhi, India, 110076
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      • New Delhi, India, 11029
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  • Italy
      • Bari, Italy, 70120
        • Not yet recruiting
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      • Florence, Italy, 50134
        • Not yet recruiting
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      • Padova, Italy, 35128
        • Not yet recruiting
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      • Roma, Italy, 00168
        • Not yet recruiting
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      • Rozzano, Italy, 20089
        • Not yet recruiting
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      • Tricase, Italy, 73039
        • Not yet recruiting
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  • Japan
      • Fukuoka, Japan, 812-8582
        • Not yet recruiting
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      • Fukuoka, Japan, 811-1347
        • Not yet recruiting
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      • Hamamatsu, Japan, 431-3192
        • Not yet recruiting
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      • Hirosaki-shi, Japan, 036-8563
        • Withdrawn
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      • Kanazawa, Japan, 920-8641
        • Not yet recruiting
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      • Kashihara-shi, Japan, 634-8522
        • Not yet recruiting
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      • Kawasaki-shi, Japan, 216-8511
        • Not yet recruiting
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      • Kita-gun, Japan, 761-0793
        • Withdrawn
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      • Kobe, Japan, 650-0017
        • Not yet recruiting
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      • Kumamoto, Japan, 860-0008
        • Not yet recruiting
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      • Kōtoku, Japan, 135-8550
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      • Nagasaki, Japan, 852-8501
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      • Nagoya, Japan, 466-8560
        • Not yet recruiting
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      • Osaka, Japan, 545-8586
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      • Osaka, Japan, 541-8567
        • Not yet recruiting
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      • Toyama, Japan, 930-0194
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      • Tsukuba, Japan, 305-8576
        • Not yet recruiting
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  • Poland
      • Gdansk, Poland, 80-952
        • Not yet recruiting
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      • Koszalin, Poland, 75-581
        • Not yet recruiting
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      • Poznan, Poland, 61-731
        • Not yet recruiting
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      • Siedlce, Poland, 08-110
        • Not yet recruiting
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      • Skórzewo, Poland, 60-185
        • Not yet recruiting
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      • Wroclaw, Poland, 53-413
        • Not yet recruiting
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      • Wroclaw, Poland, 50-556
        • Not yet recruiting
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  • South Korea
      • Seoul, South Korea, 3722
        • Not yet recruiting
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      • Seoul, South Korea, 03080
        • Not yet recruiting
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      • Seoul, South Korea, 06591
        • Not yet recruiting
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      • Seoul, South Korea, 5505
        • Not yet recruiting
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      • Seoul, South Korea, 6351
        • Not yet recruiting
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  • Spain
      • L'Hospitalet de Llobregat, Spain, 08908
        • Not yet recruiting
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      • Las Palmas de Gran Canaria, Spain, 35016
        • Not yet recruiting
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      • Madrid, Spain, 28040
        • Not yet recruiting
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      • Santander, Spain, 39008
        • Not yet recruiting
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      • Seville, Spain, 41013
        • Not yet recruiting
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  • Taiwan
      • Kaohsiung City, Taiwan, 80756
        • Recruiting
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      • Kaohsiung City, Taiwan, 83301
        • Not yet recruiting
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      • Kaohsiung City, Taiwan, 813
        • Not yet recruiting
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      • Tainan, Taiwan, 704
        • Not yet recruiting
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      • Taipei, Taiwan, 11217
        • Not yet recruiting
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      • Taoyuan, Taiwan, 333
        • Not yet recruiting
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  • Thailand
      • Bangkok, Thailand, 10700
        • Not yet recruiting
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      • Hat Yai, Thailand, 90110
        • Not yet recruiting
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  • United Kingdom
      • Bristol, United Kingdom, BS2 8ED
        • Not yet recruiting
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      • Cambridge, United Kingdom, CB2 0QQ
        • Not yet recruiting
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      • Preston, United Kingdom, PR2 9HT
        • Not yet recruiting
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      • Sheffield, United Kingdom, S10 2SJ
        • Not yet recruiting
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  • United States
    • Arkansas
      • Hot Springs, Arkansas, United States, 71913
        • Not yet recruiting
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      • Little Rock, Arkansas, United States, 72205
        • Not yet recruiting
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      • Little Rock, Arkansas, United States, 72211
        • Not yet recruiting
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    • California
      • San Francisco, California, United States, 94143
        • Not yet recruiting
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    • Illinois
      • Chicago, Illinois, United States, 60637
        • Withdrawn
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    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Not yet recruiting
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    • Missouri
      • Kansas City, Missouri, United States, 64132
        • Not yet recruiting
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    • Nebraska
      • Lincoln, Nebraska, United States, 68506
        • Not yet recruiting
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      • Omaha, Nebraska, United States, 68130
        • Not yet recruiting
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    • New York
      • Albany, New York, United States, 12208
        • Not yet recruiting
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      • New York, New York, United States, 10065
        • Not yet recruiting
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    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Not yet recruiting
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    • South Carolina
      • Myrtle Beach, South Carolina, United States, 29572
        • Not yet recruiting
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    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Not yet recruiting
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    • Texas
      • Dallas, Texas, United States, 75235
        • Not yet recruiting
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    • Virginia
      • Falls Church, Virginia, United States, 22042
        • Not yet recruiting
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    • Washington
      • Seattle, Washington, United States, 98109
        • Not yet recruiting
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      • Tacoma, Washington, United States, 98405
        • Not yet recruiting
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    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Not yet recruiting
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion criteria:

  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.

Exclusion criteria:

  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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm 1: Dato-DXd + rilvegostomig
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.
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.
Other Names:
  • Datopotamab deruxtecan
  • (Dato-DXd, DS-1062a)
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.
Other Names:
  • AZD2936
Experimental: Arm 2: Dato-DXd monotherapy
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.
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.
Other Names:
  • Datopotamab deruxtecan
  • (Dato-DXd, DS-1062a)
Active Comparator: Arm 3 (SoC): nivolumab or durvalumab or EV + pembrolizumab

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.
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.
Other Names:
  • Imfinzi, MEDI4736
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.
Other Names:
  • OPDIVO®, BMS-936558
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.
Other Names:
  • Keytruda, MK-3475
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.

Other Names:
  • Padcev®, ASG-22CE, AGS-22M6E

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
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.
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).
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.
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.
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.
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).
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).
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).
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.
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.

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

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 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).
Concentration of Dato-DXd and DXd in plasma. Concentration of rilvegostomig in serum.
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).
Time Frame: 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).
Presence of antidrug antibody (ADA) for Dato-DXd in plasma and rilvegostomig in serum (confirmatory results: positive or negative, titres).
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).
Time Frame: 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.
Proportion of participants with maintained or improved GHS/QoL as measured by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) GHS/QoL subscale (EORTC IL6) at each time point.
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.
Safety of adjuvant Dato-DXd in combination with rilvegostomig as compared with Dato-DXd monotherapy and SoC.
Time Frame: From randomization through the end of treatment (approximately up to 12 months after randomization) and through the end of safety follow-up (approximately up to 15 months after randomization).
Safety will be evaluated in terms of AEs.
From randomization through the end of treatment (approximately up to 12 months after randomization) and through the end of safety follow-up (approximately up to 15 months after randomization).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AstraZeneca

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Daiichi Sankyo

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 16, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 11, 2030

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 23, 2032

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 10, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 17, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 22, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 22, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 17, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • D763TC00001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

IPD Sharing Time Frame

Study start to completion date

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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