Urothelial CancerPhase 2/3NCT07129993

Study of Datopotamab Deruxtecan Plus Carboplatin or Cisplatin Versus Gemcitabine Plus Carboplatin or Cisplatin in Participants With Locally Advanced or Metastatic Urothelial Carcinoma

A Phase 2/3 study testing Dato-DXd, Carboplatin and Cisplatin in people with Urothelial Cancer and Bladder Cancer, run by Daiichi Sankyo at 100 sites in 7 countries.

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Sites and contacts

Official record

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Trial summary

This is a global, multicenter, randomized, open-label, Phase 2/3 study of Dato-DXd plus carboplatin or cisplatin versus gemcitabine plus carboplatin or cisplatin in participants with la/mUC who progressed during or after EV plus pembrolizumab combination treatment. This trial will start with part A, Phase 2. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Urothelial Cancer, Bladder Cancer
What is being tested?: Dato-DXd, Carboplatin and Cisplatin
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 630 participants
Where: 100 sitesin 7 countries
Study dates: 26 Sep 2025to 22 Jan 2030
Phase: Phase 2/3
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

Adult ≥18 years at the time the ICF is signed (if the legal age of consent is > 18 years old, then follow the local regulatory requirements).
Histologically or cytologically confirmed unresectable or locally advanced (T4b, any N; or any T, N 2-3) or metastatic (any T, any N, M1) urothelial carcinoma of the bladder, renal pelvis, ureter, or urethra. Participants with urothelial carcinoma (transitional cell) with squamous differentiation or mixed cell types are eligible if the histology is predominantly urothelial as specified in the protocol.
Must provide tumor tissue sample from archival tissue or newly obtained pretreatment biopsy for exploratory biomarker testing. Tumor tissue sample should not be collected from a lesion that was irradiated unless documentation can be provided confirming that the tumor tissue was collected at least 3 months after radiation and the lesion increased/appeared since radiation occurred. Tumor tissue must be of sufficient quantity (as defined in the Laboratory Manual).
Archival tissue collected after the most recent anticancer treatment and within 12 months before the informed consent date is preferred.
Must be considered eligible to receive cisplatin- or carboplatin-containing chemotherapy, in the investigator's judgment. Participants eligible for cisplatin will receive cisplatin. If a participant received gemcitabine, carboplatin, or cisplatin for early UC in the adjuvant/neoadjuvant setting, the decision to rechallenge the participant with platinum therapy will be at the discretion of the investigator. Participants only receive carboplatin if they are ineligible for cisplatin. Participants are cisplatin-ineligible if they meet any of the following criteria: a. GFR <60 mL/min (GFR may be estimated by calculated CrCl using the Cockcroft-Gault formula, Modification of Diet in Renal Disease, or 24-hour urine)
For Phase 2 part:

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Participants with a GFR <60 mL/min but ≥50 mL/min but have no other cisplatin ineligibility criteria (items b, c, and d) may be considered cisplatin-eligible based on the investigator's clinical judgment.
For Phase 3 Part:
Participants with borderline renal function CrCl ≥40 mL/min to <60 mL/min who have no other cisplatin ineligibility criteria (items b, c, and d) may receive cisplatin using a split-dose regimen, administered as cisplatin 35 mg/m^2 on Days 1 and 8 of each 21-day cycle, for a maximum of 4 to 6 cycles.
In participants with CrCl ≥50 mL/min to <60 mL/min, full-dose cisplatin may also be administered at the investigator's discretion, based on the overall clinical assessment.
The dosing schedule and dose level for Dato-DXd or gemcitabine are not altered when combined with either split-dose or full-dose cisplatin.
For both Phase 2 and Phase 3:
NCI-CTCAE Grade ≥2 audiometric hearing loss c. NCI-CTCAE Grade ≥2 peripheral neuropathy d. NYHA Class III heart failure
Must have experienced radiographic progression or relapse during or after 1L of EV (or other agents with a vedotin payload) and pembrolizumab (or other PD-1/PD-L1 inhibitors).
Participants who discontinued EV (or other agents with a vedotin payload) and pembrolizumab (or other PD-1/PD-L1 inhibitors) in 1L due to toxicity are eligible if they have experienced disease progression following discontinuation. Participant who received EV (or other agents with a vedotin payload) plus pembrolizumab (or other PD-1/PD-L1) inhibitors in a neoadjuvant/adjuvant setting and progressed during treatment or within 12 months of treatment completion will also be considered for enrollment, after approval by the Sponsor's Medical Monitor or Sponsor's designee.

Who cannot join

Has had prior systemic therapy other than the combination of EV and pembrolizumab for la/mUC. The following participants may be considered eligible after approval by the Sponsor's Medical Monitor or Sponsor's designee.
Participant who progressed during or after treatments with assets that include either anti-Nectin 4 or vedotin payload (MMAE or other microtubule inhibitors) combined with PD1/PD-L1 inhibitors in 1L la/mUC.
Treatment with any of the following:
History of an allogeneic bone marrow or solid organ transplant.
Concomitant treatment with any prohibited medications in this protocol.
Prior TROP2 directed ADC therapy.

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Uncontrolled or significant cardiovascular disease, including:
QTcF interval >470 ms based on the average of triplicate 12-lead (ECG per local read) at screening.
Screening myocardial infarction within 6 months prior to randomization.
Uncontrolled angina pectoris within 6 months prior to randomization.
NYHA Class 3 or 4 congestive heart failure at screening.
Uncontrolled hypertension (resting systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg within 28 days before randomization that is not resolved despite maximal medical therapy).
Has a 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 compromise as judged by the investigator resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (eg, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc.) or any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement (eg, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc.), or prior complete pneumonectomy.
Toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet improved to NCI-CTCAE version 5.0 Grade ≤1 or baseline. Note: Participants may be enrolled with chronic, stable Grade 2 toxicities (defined as no worsening to Grade >2 for at least 3 months prior to randomization and managed with standard of care treatment) which the investigator deems related to previous anticancer therapy, comprised of (including but not limited to):
Anticancer therapy-induced neuropathy b. Residual toxicities from prior immunotherapy treatment: Grade 1 or Grade 2 endocrinopathies which may include:
Hypothyroidism/ hyperthyroidism
Type I diabetes
Hyperglycemia
Adrenal insufficiency
Adrenalitis c. Skin hypopigmentation (vitiligo)

Trial locations and contacts

100 sites in 7 countries. Contact the study team or a site near you to ask about taking part.

Contact for Trial Information contact

908-992-6400

CTRinfo_us@daiichisankyo.com

Country

City, postcode or hospital

Sites recruiting now only

100 sites in 7 countries

United States38 sites, 8 recruiting

Research Site
Atlanta, Georgia, 30342
Active, not recruiting
Research Site
Aurora, Colorado, 80012
Active, not recruiting
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Austin, Texas, 33322
Active, not recruiting
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Boston, Massachusetts, 02216
Active, not recruiting
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Chapel Hill, North Carolina, 27514
Recruiting
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Charlottesville, Virginia, 22908
Active, not recruiting
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Dallas, Texas, 75246
Recruiting
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Dallas, Texas, 75390
Active, not recruiting
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Effingham, Illinois, 62401
Active, not recruiting
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Fullerton, California, 92835
Active, not recruiting
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Germantown, Tennessee, 38138
Active, not recruiting
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Glendale, California, 91204
Active, not recruiting
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Grand Rapids, Michigan, 49546
Recruiting
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La Jolla, California, 92093
Active, not recruiting
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Largo, Maryland, 20774
Active, not recruiting
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Locust Grove, Georgia, 30248
Active, not recruiting
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Los Angeles, California, 90024
Recruiting
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Madison, Wisconsin, 53715
Active, not recruiting
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Memphis, Tennessee, 38120
Active, not recruiting
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Monroeville, Pennsylvania, 15146
Active, not recruiting
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Myrtle Beach, South Carolina, 29572
Active, not recruiting
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Nashville, Tennessee, 37203
Recruiting
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New York, New York, 10029
Active, not recruiting
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Niles, Illinois, 60714
Recruiting
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Norfolk, Virginia, 23502-1871
Recruiting
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Orange, California, 92868
Active, not recruiting
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Orange City, Florida, 32763
Active, not recruiting
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Peoria, Illinois, 61615
Recruiting
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Philadelphia, Pennsylvania, 19107
Active, not recruiting
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Portland, Oregon, 97227
Active, not recruiting
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Providence, Rhode Island, 02906
Active, not recruiting
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Raleigh, North Carolina, 27610
Active, not recruiting
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Rochester, Minnesota, 55905
Active, not recruiting
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San Francisco, California, 94158
Active, not recruiting
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Spokane, Washington, 99208
Active, not recruiting
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St Louis, Missouri, 63110
Active, not recruiting
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St. Petersburg, Florida, 33701
Active, not recruiting
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Tamarac, Florida, 62269
Active, not recruiting

Other trials in United States

France27 sites, 12 recruiting

Research Site
Angers, 49055
Active, not recruiting
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Bordeaux, 33075
Recruiting
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Brest
Recruiting
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Calais
Active, not recruiting
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Cedex 10
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Créteil
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Grenoble
Active, not recruiting
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La Chaussée-Saint-Victor
Active, not recruiting
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La Roche-sur-Yon
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Le Mans
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Lyon
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Marseille, 13273
Active, not recruiting
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Marseille
Active, not recruiting
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Montpellier
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Nantes
Active, not recruiting
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Nîmes
Active, not recruiting
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Paris
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Paris
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Pierre-Bénite, 69310
Active, not recruiting
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Poitiers
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Quint-Fonsegrives
Active, not recruiting
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Reims
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Saint-Etienne
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Saint-Herblain
Active, not recruiting
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Strasbourg, 67065
Active, not recruiting
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Toulouse
Active, not recruiting
Research Site
Vandœuvre-lès-Nancy
Recruiting

Other trials in France

Japan20 sites, 7 recruiting

Research Site
Bunkyō City, 113-8519
Active, not recruiting
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Bunkyō City
Active, not recruiting
Research Site
Fukuoka, 812-8582
Active, not recruiting
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Fukuoka
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Hirosaki-shi
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Kanazawa
Active, not recruiting
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Kawasaki
Recruiting
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Kōtoku, 135-8550
Recruiting
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Kumamoto
Active, not recruiting
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Kyoto, 606-8507
Active, not recruiting
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Nagoya
Recruiting
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Niigata
Active, not recruiting
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Okayama, 700-8558
Recruiting
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Osaka
Recruiting
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Osakasayama-shi, 589-8511
Recruiting
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Sapporo
Active, not recruiting
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Shinjuku-ku
Active, not recruiting
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Toyama
Active, not recruiting
Research Site
Tsukuba, 305-8576
Active, not recruiting
Research Site
Ube-shi, 755-8505
Recruiting

Other trials in Japan

Austria5 sites

Research Site
Graz, 8036
Active, not recruiting
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Krems
Active, not recruiting
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Linz, 4010
Active, not recruiting
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Salzburg, 5020
Active, not recruiting
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Vienna
Active, not recruiting

Other trials in Austria

Germany4 sites, 1 recruiting

Research Site
Eisleben Lutherstadt, 06295
Active, not recruiting
Research Site
Herne, 44625
Active, not recruiting
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Nürtingen
Recruiting
Research Site
Stuttgart, 70174
Active, not recruiting

Other trials in Germany

China3 sites, 1 recruiting

Research Site
Beijing, 100142
Recruiting
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Chengdu
Active, not recruiting
Research Site
Guangzhou
Active, not recruiting

Other trials in China

Italy3 sites

Research Site
Naples
Active, not recruiting
Research Site
Roma
Active, not recruiting
Research Site
Rozzano
Active, not recruiting

Other trials in Italy

About this study

Official title: A Randomized, Open-Label, Phase 2/3 Study of Datopotamab Deruxtecan (Dato-DXd) Plus Carboplatin or Cisplatin Versus Gemcitabine Plus Carboplatin or Cisplatin in Participants With Locally Advanced or Metastatic Urothelial Carcinoma (la/mUC) Who Progressed During or After Enfortumab Vedotin (EV) Plus Pembrolizumab Combination Treatment TROPION-Urothelial03 (TU03)

This trial will start with part A, Phase 2. During part A, Phase 2, preliminary efficacy and safety will be assessed, and the recommended Phase 3 dose (RP3D) will be identified when the data allow sufficient assessment of activity, safety, and tolerability. The Phase 3 part will start contingent upon the assessment in the Phase 2 part, taking into consideration the totality of information.

Conditions: Urothelial Cancer, Bladder Cancer
Being tested: Dato-DXd, Carboplatin, Cisplatin, Gemcitabine
Keywords: Urothelial Carcinoma, Dato-DXd, TROPION, DS-1062a, Datopotamab Deruxtecan
Medical subject headings: Urinary Bladder Neoplasms, Carcinoma, Transitional Cell

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 will be administered as an intravenous (IV) infusion every three weeks (Q3W) at a dose of 4 mg/kg or 6 mg/kg in Part A or RP3D in Part B
CarboplatinDrug
Carboplatin will be administered as an intravenous (IV) infusion every three weeks (Q3W) at a dose of AUC 4.5 or 5.0 mg•min/mL
CisplatinDrug
Cisplatin will be administered as an intravenous (IV) infusion every three weeks (Q3W) at a dose of 70 mg/m^2 (Phase 2) or 70 mg/m^2 on Day 1 or 35 mg/m^2 on Day 1 and Day 8 each 21- day cycle (Phase 3)
GemcitabineDrug
Gemcitabine will be administered as an IV infusion at a dose of 1000 mg/m^2 on Day 1 and 8 of every 3 week cycle.

Study groups in NCT07129993
Study group	Role	What they receive
Part A (Phase 2): Dato-DXd, 4 mg/kg with Platinum	Experimental	Participants will receive Dato-DXd in combination with platinum (carboplatin or cisplatin). The RP3D will be determined using data collected from Part A. Receives: Drug: Dato-DXd; Drug: Carboplatin; Drug: Cisplatin
Part A (Phase 2): Dato-DXd, 6 mg/kg with Platinum	Experimental	Participants will receive Dato-DXd in combination with platinum (carboplatin or cisplatin). The RP3D will be determined using data collected from Part A. Receives: Drug: Dato-DXd; Drug: Carboplatin; Drug: Cisplatin
Part B (Phase 3): Dato-DXd, RP3D with Platinum	Experimental	Participants will receive Dato-DXd at the RP3D in combination with platinum (carboplatin or cisplatin). Receives: Drug: Dato-DXd; Drug: Carboplatin; Drug: Cisplatin
Part B (Phase 3): Gemcitabine with Platinum	Active comparator	Participants will receive Gemcitabine in combination with platinum (carboplatin or cisplatin). Receives: Drug: Carboplatin; Drug: Cisplatin; Drug: Gemcitabine

What is being measured

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

Overall Response Rate - Part A (Phase 2)
Overall Response Rate (ORR) is defined as the proportion of participants with a Best Overall Response (BOR) of confirmed Complete Response (CR) or confirmed Partial Response (PR). As assessed by investigator per RECIST v1.1
Measured: From Phase 2 randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, up to approximately 34 months
Progression Free Survival as Assessed by Blinded Independent Central Review (BICR) - Part B (Phase 3)
Progression Free Survival (PFS) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first. As assessed by BICR per RECIST v1.1
Measured: From Phase 3 randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, up to approximately 38 months
Overall Survival - Part B (Phase 3)
Overall Survival (OS) is defined as the time from randomization to death due to any cause.
Measured: From Phase 3 randomization to death due to any cause, up to approximately 38 months

Secondary outcomes (3)

Duration of Response - Part A (Phase 2)
Duration of Response (DoR) is defined as the time from the date of first documentation of objective tumor response (confirmed CR or confirmed PR) to the date of the first documented radiographic disease progression or death due to any cause, whichever occurs first in responding participants. As assessed by investigator per RECIST v1.1
Measured: From the date of first documentation of objective tumor response to the date of the first documented radiographic disease progression or death due to any cause, whichever occurs first in Phase 2, up to approximately 34 months
Progression Free Survival as Assessed by Investigator - Part B (Phase 3)
PFS is defined as the time interval from the date of randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first. As assessed by investigator per RECIST v1.1
Measured: From Phase 3 randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, up to approximately 38 months
Overall Response Rate - Part B (Phase 3)
ORR is defined as the proportion of participants with a BOR of confirmed CR or confirmed PR. As assessed by BICR and investigator per RECIST V1.1
Measured: From Phase 3 randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, up to approximately 38 months

Timeline

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

26 Sep 202522 Jan 2030

First posted19 Aug 2025
Study start26 Sep 2025
Primary completion1 Jun 2029 (estimated)
Study completion22 Jan 2030 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Urothelial CancerStudies of the same condition, open and under way.
More trials run by Daiichi SankyoThe 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 2/3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 630 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07129993
Sponsor's protocol ID: DS1062-328
Status last verified: Aug 2026
First submitted: 12 Aug 2025
Last updated: 20 Aug 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Publications

Galsky MD, Drakaki A, Basu A, McGregor B, Bedke J, Loriot Y, Kikuchi E, Guo J, Garmezy B, Sridhar SS, Singh P, Koshkin VS, Fleming M, Klauss G, Lin D, Liu C, Apolo AB, Powles T. TROPION-Urothelial03: a phase II/III study of datopotamab deruxtecan (Dato-DXd) for locally advanced or metastatic urothelial carcinoma. Future Oncol. 2026 May;22(12):1387-1396. doi: 10.1080/14796694.2026.2663956. Epub 2026 May 16.
PubMed 42142358

Interested in taking part?

Contact for Trial Information

908-992-6400

CTRinfo_us@daiichisankyo.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

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Study at a glance

From the registry record, last updated by the sponsor on 20 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Open-Label, Phase 2/3 Study of Datopotamab Deruxtecan (Dato-DXd) Plus Carboplatin or Cisplatin Versus Gemcitabine Plus Carboplatin or Cisplatin in Participants With Locally Advanced or Metastatic Urothelial Carcinoma (la/mUC) Who Progressed During or After Enfortumab Vedotin (EV) Plus Pembrolizumab Combination Treatment TROPION-Urothelial03 (TU03)
ClinicalTrials.gov ID: NCT07129993
Acronym / sponsor ID: DS1062-328
Conditions: Urothelial Cancer, Bladder Cancer
Keywords: Urothelial Carcinoma, Dato-DXd, TROPION, DS-1062a, Datopotamab Deruxtecan
Phase: Phase 2/3
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 630 participants (estimated)
Lead sponsor: Daiichi SankyoIndustry (pharma, biotech, devices)
Collaborators: AstraZeneca
Study start: 26 Sep 2025 (actual)
Primary completion: 1 Jun 2029 (estimated)
Study completion: 22 Jan 2030 (estimated)
First posted: 19 Aug 2025 (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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Part A (Phase 2): Dato-DXd, 4 mg/kg with Platinum	Experimental	Drug: Dato-DXd, Drug: Carboplatin, Drug: CisplatinParticipants will receive Dato-DXd in combination with platinum (carboplatin or cisplatin). The RP3D will be determined using data collected from Part A.
Part A (Phase 2): Dato-DXd, 6 mg/kg with Platinum	Experimental	Drug: Dato-DXd, Drug: Carboplatin, Drug: CisplatinParticipants will receive Dato-DXd in combination with platinum (carboplatin or cisplatin). The RP3D will be determined using data collected from Part A.
Part B (Phase 3): Dato-DXd, RP3D with Platinum	Experimental	Drug: Dato-DXd, Drug: Carboplatin, Drug: CisplatinParticipants will receive Dato-DXd at the RP3D in combination with platinum (carboplatin or cisplatin).
Part B (Phase 3): Gemcitabine with Platinum	Active comparator	Drug: Carboplatin, Drug: Cisplatin, Drug: GemcitabineParticipants will receive Gemcitabine in combination with platinum (carboplatin or cisplatin).

Who may qualify

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

Key inclusion criteria (15 listed)

Adult ≥18 years at the time the ICF is signed (if the legal age of consent is > 18 years old, then follow the local regulatory requirements).
Histologically or cytologically confirmed unresectable or locally advanced (T4b, any N; or any T, N 2-3) or metastatic (any T, any N, M1) urothelial carcinoma of the bladder, renal pelvis, ureter, or urethra. Participants with urothelial carcinoma (transitional cell) with squamous differentiation or mixed cell types are eligible if the histology is predominantly urothelial as specified in the protocol.
Must provide tumor tissue sample from archival tissue or newly obtained pretreatment biopsy for exploratory biomarker testing. Tumor tissue sample should not be collected from a lesion that was irradiated unless documentation can be provided confirming that the tumor tissue was collected at least 3 months after radiation and the lesion increased/appeared since radiation occurred. Tumor tissue must be of sufficient quantity (as defined in the Laboratory Manual).
Archival tissue collected after the most recent anticancer treatment and within 12 months before the informed consent date is preferred.
Must be considered eligible to receive cisplatin- or carboplatin-containing chemotherapy, in the investigator's judgment. Participants eligible for cisplatin will receive cisplatin. If a participant received gemcitabine, carboplatin, or cisplatin for early UC in the adjuvant/neoadjuvant setting, the decision to rechallenge the participant with platinum therapy will be at the discretion of the investigator. Participants only receive carboplatin if they are ineligible for cisplatin. Participants are cisplatin-ineligible if they meet any of the following criteria: a. GFR <60 mL/min (GFR may be estimated by calculated CrCl using the Cockcroft-Gault formula, Modification of Diet in Renal Disease, or 24-hour urine)

Key exclusion criteria (21 listed)

Has had prior systemic therapy other than the combination of EV and pembrolizumab for la/mUC. The following participants may be considered eligible after approval by the Sponsor's Medical Monitor or Sponsor's designee.
Participant who progressed during or after treatments with assets that include either anti-Nectin 4 or vedotin payload (MMAE or other microtubule inhibitors) combined with PD1/PD-L1 inhibitors in 1L la/mUC.
Treatment with any of the following:
Uncontrolled or significant cardiovascular disease, including:
QTcF interval >470 ms based on the average of triplicate 12-lead (ECG per local read) at screening.

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 DeruxtecanDato-DXd will be administered as an intravenous (IV) infusion every three weeks (Q3W) at a dose of 4 mg/kg or 6 mg/kg in Part A or RP3D in Part B	Drug	Part A (Phase 2): Dato-DXd, 4 mg/kg with Platinum, Part A (Phase 2): Dato-DXd, 6 mg/kg with Platinum, Part B (Phase 3): Dato-DXd, RP3D with Platinum
CarboplatinCarboplatin will be administered as an intravenous (IV) infusion every three weeks (Q3W) at a dose of AUC 4.5 or 5.0 mg•min/mL	Drug	Part A (Phase 2): Dato-DXd, 4 mg/kg with Platinum, Part A (Phase 2): Dato-DXd, 6 mg/kg with Platinum, Part B (Phase 3): Dato-DXd, RP3D with Platinum, Part B (Phase 3): Gemcitabine with Platinum
CisplatinCisplatin will be administered as an intravenous (IV) infusion every three weeks (Q3W) at a dose of 70 mg/m^2 (Phase 2) or 70 mg/m^2 on Day 1 or 35 mg/m^2 on Day 1 and Day 8 each 21- day cycle (Phase 3)	Drug	Part A (Phase 2): Dato-DXd, 4 mg/kg with Platinum, Part A (Phase 2): Dato-DXd, 6 mg/kg with Platinum, Part B (Phase 3): Dato-DXd, RP3D with Platinum, Part B (Phase 3): Gemcitabine with Platinum
GemcitabineGemcitabine will be administered as an IV infusion at a dose of 1000 mg/m^2 on Day 1 and 8 of every 3 week cycle.	Drug	Part B (Phase 3): Gemcitabine with Platinum

Primary outcome

Overall Response Rate - Part A (Phase 2)
Time frame: From Phase 2 randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, up to approximately 34 months
Overall Response Rate (ORR) is defined as the proportion of participants with a Best Overall Response (BOR) of confirmed Complete Response (CR) or confirmed Partial Response (PR). As assessed by investigator per RECIST v1.1
Progression Free Survival as Assessed by Blinded Independent Central Review (BICR) - Part B (Phase 3)
Time frame: From Phase 3 randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, up to approximately 38 months
Progression Free Survival (PFS) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first. As assessed by BICR per RECIST v1.1
Overall Survival - Part B (Phase 3)
Time frame: From Phase 3 randomization to death due to any cause, up to approximately 38 months
Overall Survival (OS) is defined as the time from randomization to death due to any cause.

3 secondary outcomes

Duration of Response - Part A (Phase 2)
Time frame: From the date of first documentation of objective tumor response to the date of the first documented radiographic disease progression or death due to any cause, whichever occurs first in Phase 2, up to approximately 34 months
Progression Free Survival as Assessed by Investigator - Part B (Phase 3)
Time frame: From Phase 3 randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, up to approximately 38 months
Overall Response Rate - Part B (Phase 3)
Time frame: From Phase 3 randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, up to approximately 38 months

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 20 Aug 2026.
Derived from this study: PubMed 42142358Galsky MD, Drakaki A, Basu A, McGregor B, Bedke J, Loriot Y, Kikuchi E, Guo J, Garmezy B, Sridhar SS, Singh P, Koshkin VS, Fleming M, Klauss G, Lin D, Liu C, Apolo AB, Powles T. TROPION-Urothelial03: a phase II/III study of datopotamab deruxtecan (Dato-DXd) for locally advanced or metastatic urothelial carcinoma. Future Oncol. 2026 May;22(12):1387-1396. doi: 10.1080/14796694.2026.2663956. Epub 2026 May 16.
Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

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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.

Contact for Trial Information contact

908-992-6400

CTRinfo_us@daiichisankyo.com

100 sites in 7 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Dato-DXd, Carboplatin and Cisplatin in people with Urothelial Cancer and Bladder Cancer, run by Daiichi Sankyo at 100 sites in 7 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 15 inclusion and 21 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 20 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 100 sites in United States, France, Japan, Austria, Germany and 2 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 combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 Contact for Trial Information (908-992-6400, CTRinfo_us@daiichisankyo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate - Part A (Phase 2) (time frame: From Phase 2 randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, up to approximately 34 months). The study lists 3 primary outcomes in all. 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 NCT07129993, which also lists 1 linked publication.

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 20 Aug 2026.