Adjuvant Datopotamab Deruxtecan with Drug Combination in Patients with High‑Risk Muscle‑Invasive Urothelial Carcinoma

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What is this study about?

The study focuses on High-risk muscle invasive urothelial carcinoma, a form of bladder or upper‑tract cancer that has grown into the muscle layer and carries a high chance of coming back after surgery. The main aim is to determine whether a new treatment approach can keep the disease from returning better than the current standard options.

Participants will receive an intravenous infusion of the experimental combination of Datopotamab deruxtecan and Rilvegostomig, given as an adjuvant therapy, meaning it is administered after the tumor has been surgically removed. The comparison groups will receive one of the existing intravenous medicines such as nivolumab, durvalumab, enfortumab vedotin or pembrolizumab. The study will measure success primarily by disease free survival, which is the length of time a person lives without any sign of the cancer returning, using the standardized assessment method called RECIST 1.1 to evaluate any changes in tumor size.

After surgery, eligible participants are randomly assigned to receive either the new drug combination or one of the standard treatments. The assigned medication is given by IV infusion at regular intervals over several months, and participants attend scheduled clinic visits for physical exams, blood tests, and imaging scans to monitor for any recurrence of cancer or side effects. The study continues until a predefined follow‑up period is completed or until the participant experiences disease recurrence or other discontinuing events.

1 enrollment and randomisation

after providing informed consent you are assigned a random number that determines which treatment group you will follow in the study.

2 baseline assessments

before the first dose you undergo a physical examination, blood tests, and imaging scans to document the current status of your cancer.

these assessments are used later to compare any changes that occur during treatment.

3 initiation of study medication

if you are placed in the experimental arm you receive datopotamab deruxtecan together with rilvegostomig by intravenous infusion.

if you are placed in a comparator arm you receive one of the following intravenous medicines: nivolumab, durvalumab, enfortumab vedotin combined with pembrolizumab.

the dose for each medicine is expressed in milligrams or milligrams per kilogram, but the exact amount and schedule are defined by the study protocol and are not specified in the provided information.

4 treatment cycles

the assigned medicines are given repeatedly according to a cycle defined by the study, typically by infusion over a set period of time.

each cycle is separated by a resting interval that allows your body to recover before the next infusion.

the total length of treatment continues until disease recurrence, unacceptable side effects, or the end of the planned treatment period.

5 regular monitoring visits

at scheduled intervals you attend clinic visits for safety checks, blood tests, and evaluation of any side effects.

additional imaging scans are performed to monitor the status of the cancer.

any background medications such as mycophenolate mofetil (taken by mouth) or infliximab (given by infusion) are continued as instructed.

6 disease assessment

the investigator compares current imaging results with the baseline using the recist 1.1 criteria, which measure changes in tumor size.

the primary outcome measured is disease‑free survival, defined as the time from randomisation until cancer returns or death from any cause.

7 continuation or discontinuation of treatment

treatment proceeds as long as the cancer does not recur, side effects remain manageable, and you continue to meet study requirements.

if disease recurrence, severe toxicity, or other protocol‑specified reasons occur, study medication is stopped.

8 post‑treatment follow‑up

after stopping the study medication you remain under observation for a period defined by the study.

follow‑up visits include clinical examinations, laboratory tests, and imaging to record long‑term outcomes such as overall survival and any late side effects.

Who Can Join the Study?

You must be older than 18 years when you sign the Informed Consent Form (ICF).
Your cancer must be confirmed by a microscope as muscle invasive urothelial carcinoma (MIUC) that started in the bladder or the upper urinary tract (kidney pelvis or ureter).
You must have had an R0 radical resection (complete surgery that removes all visible tumor with clean edges) between 28 and 120 days before randomisation, with negative margins (no cancer at the edges of the removed tissue) and no leftover or spreading (metastatic) cancer.
Pathology must show a high‑risk of recurrence based on tumor stage and treatment history:
- If you did not receive any treatment before surgery, the tumor must be stage T3–T4a with no lymph‑node involvement (N0), or any stage with positive lymph nodes (N+).
- If you received treatment before surgery (neoadjuvant therapy), the tumor after surgery must be stage ypT2–ypT4a, or any stage with positive lymph nodes (ypN+).
At the screening visit, doctors must find no evidence of disease (no cancer visible on tests).
You need an ECOG performance status of 0 or 1, meaning you are fully active (0) or able to do light work but not strenuous activity (1), and this level must not have gotten worse in the two weeks before randomisation.
You must have a life expectancy of more than 12 weeks at the time of screening.
A saved piece of the tumor from your surgery (archival surgical tumour sample) must be available for central laboratory testing before randomisation.
Your blood tests and organ checks must show adequate organ and bone marrow function (normal blood counts and organ health) within 28 days before randomisation.

Who Cannot Join the Study?

Cannot have a tumor that is mainly or entirely a high‑grade neuroendocrine carcinoma, a rare and aggressive type of cancer.
Cannot have any active or uncontrolled infection (including tuberculosis) that still needs medication at the time of randomisation.
Cannot have a history of non‑infectious interstitial lung disease (ILD) or pneumonitis (lung inflammation), especially if it required steroids, is still present, or cannot be ruled out by a scan.
Cannot have severely reduced lung function that makes breathing very difficult.
Cannot have a resting heart‑rate‑corrected QT interval (QTcF) longer than 470 milliseconds on an ECG, which can indicate a risk of abnormal heart rhythms.
Cannot have uncontrolled or serious heart problems.
Cannot have an autoimmune or inflammatory disease that needed systemic (whole‑body) treatment in the past five years.
Cannot have previously received any therapy that targets TROP2, other antibody‑drug conjugates (ADCs) with deruxtecan, anti‑cancer vaccines, anti‑TIGIT drugs, or similar immune‑targeting cancer treatments.
Cannot have taken medicines that suppress the immune system within 14 days before being assigned to a treatment group.
Cannot have a known severe allergic (hypersensitivity) reaction to any of the study drugs.
Cannot be ineligible to receive at least one standard‑of‑care treatment according to local rules.
Cannot have had a partial removal of the bladder (partial cystectomy) or a partial removal of a kidney (partial nephrectomy) for bladder or kidney cancer.
Cannot be currently pregnant, breastfeeding, or planning to become pregnant.
Cannot have received any additional chemotherapy or radiation therapy after surgery for urothelial cancer.
Cannot have severe or uncontrolled overall illnesses, a history of organ transplant or stem‑cell transplant, serious mental health or social problems, or ongoing substance abuse.
Cannot have a history of serious eye disease affecting the cornea.
Cannot have another primary cancer, unless it was treated with curative intent, has no active disease, and was diagnosed more than two years ago with low risk of coming back.
Cannot have ongoing side effects from previous cancer treatment that are worse than mild (grade 1), except for hair loss; stable moderate side effects (grade 2) are allowed only if unchanged for at least three months and well‑managed.
Cannot have an active or uncontrolled hepatitis B or hepatitis C infection.
Cannot have HIV infection that is not well‑controlled with medication.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
IRCCS Humanitas Research Hospital	Rozzano	Italy
Azienda Ospedaliero Universitaria Careggi	Florence	Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	Italy
Uniwersytecki Szpital Kliniczny Im Jana Mikulicza Radeckiego We Wroclawiu	Wroclaw	Poland
Szpital Wojewodzki Im. Mikolaja Kopernika W Koszalinie	Koszalin	Poland

Other Sites

Site Name	City	Country
Complejo Hospitalario Universitario Insular Materno Infantil	Las Palmas De Gran Canaria	Spain
Azienda Universitaria Ospedaliera Consorziale Policlinico Bari	Bari	Italy
Mazowiecki Szpital Wojewodzki Im. Sw. Jana Pawła II W Siedlcach Sp. z o.o.	Siedlce	Poland
Idpfviex Oqqvcaceii Vyohsw	Padua	Italy
Imespoem Rjkuocxg Dw Cuvsyd Dr Mfqcfourimc	Montpellier	France
Pmb Fpjpnucbgr Ds Cfhtp E Rsjkstkjp Csqe G Padqnz	Tricase	Italy
Vtbzwc dfc Rghnm Uyzkhirbty Hbyffnqs	Sevilla	Spain
Hlqmzwxi Cjqnoup Sot Ckorei	Madrid	Spain
Ghmdrw Hmakwthvbpk Ucglwweoyhvup Pfogu Ptktnniwqbg Ea Neodftkgwjxd	Paris	France
Cobuqt Hxgslaoxiwo Upalrkneihrnn Dk Pxwbuzts	Poitiers	France
Cwjihb Hwmmonhkjad Ltry Sxm	Pierre Benite	France
Hjlahxxz Uroqptpxguurl Mwfvfmo Df Vmqpjdjosj	Santander	Spain
Idzimfzl Clpnur Dbxentytpaggyzgln	L'hospitalet De Llobregat	Spain
Hwmvjjpr Upgvexvrtvbajs Svqnkiyhqb &hhtlpi Hnstboh db Hyisnghzzff	STRASBOURG, Alsace	France
Acsvtim Spx z ouic	Poznan	Poland
Uqwvtfxnmyvdov Cqmiejq Kajeksivv	Gdansk	Poland
Dvstvaznrydv Ciokxil Oizjerqin Pisqgqdexyxd I Hvguyceiudg	Wroclaw	Poland
Crvsubci Rpfuqyij Cvkfgf Sam z olkt Myovnxk slhnk	Poznan	Poland

Trial status

Country	Status	Recruitment Start
France	Not yet recruiting	01.10.2026
Italy	Not yet recruiting	01.10.2026
Poland	Not yet recruiting	01.10.2026
Spain	Not yet recruiting	01.10.2026

Trial locations

Investigated Drugs:

Rilvegostomig is an investigational drug given by IV infusion. In this trial it is combined with another investigational therapy to see if the pair can better prevent cancer from coming back after surgery.

Datopotamab deruxtecan is a new targeted therapy that is delivered through an IV drip. It works by attaching to a specific protein on cancer cells and delivering a chemotherapy payload directly to those cells, aiming to kill the tumor while sparing normal tissue.

Enfortumab vedotin is an approved antibody‑drug conjugate that is given intravenously. It targets a protein found on bladder cancer cells and carries a chemotherapy drug into the cancer, helping to destroy the tumor. In this study it is used as part of the standard‑of‑care comparison.

Durvalumab is an immunotherapy drug administered by IV infusion. It helps the body’s immune system recognize and attack cancer cells by blocking a protein called PD‑L1. It serves as one of the standard‑of‑care options in the comparison arm.

Nivolumab is another IV immunotherapy that works by releasing the brakes on the immune system, allowing it to fight cancer more effectively. It is also used as a standard‑of‑care option in the control arm of the trial.

Pembrolizumab is an IV‑administered immune checkpoint inhibitor that blocks the PD‑1 pathway, helping the immune system to detect and kill cancer cells. In this study it is combined with other drugs as part of the standard‑of‑care regimen.

Mycophenolate mofetil is an oral medication that suppresses the immune system. It is given to participants to help control any immune‑related side effects that may arise from the cancer treatments.

Infliximab is an IV drug that reduces inflammation by blocking a molecule called TNF‑α. It is used in the trial to manage severe inflammatory reactions that could occur during therapy.

Investigated Diseases:

Transitional cell carcinoma

High-risk muscle‑invasive urothelial carcinoma of the bladder or upper urinary tract – This cancer begins in the lining of the bladder, renal pelvis, or ureter and has grown into the muscle layer of the urinary tract wall. Being high‑risk means the tumor cells have a greater tendency to spread beyond the original site. The disease can recur locally within the urinary tract or appear in distant areas of the body. As it progresses, cancer may extend into surrounding tissues and nearby lymph nodes. Ongoing observation after surgery aims to detect any new growths as early as possible.

Trial ID:

2025-525030-57-00

Protocol code:

D763TC00001

Trial Phase:

Therapeutic confirmatory (Phase III)

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Adjuvant Datopotamab Deruxtecan with Drug Combination in Patients with High‑Risk Muscle‑Invasive Urothelial Carcinoma

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?