Study of Datopotamab Deruxtecan for Advanced Urothelial Cancer
This study is testing two different treatment combinations for locally advanced or metastatic urothelial carcinoma (a type of bladder cancer). You might be eligible if your cancer has progressed after previous treatment with EV plus pembrolizumab. The study compares Datopotamab Deruxtecan (Dato-DXd) plus carboplatin or cisplatin, against gemcitabine plus carboplatin or cisplatin. Researchers will look at how many people respond to the treatment (Overall Response Rate), how long people live without their cancer growing (Progression Free Survival), and how long people live overall (Overall Survival). The study aims to enroll 630 participants.
- Study design
- This is a global, multi-center, randomized, open-label Phase 2/3 study. It will compare two different treatment combinations in approximately 630 participants.
- What's involved
- Not specified in the trial record.
- Compensation
- Not stated in the trial record.
- Follow-up
- Participants in Phase 2 will be followed for up to approximately 34 months. Participants in Phase 3 will be followed for up to approximately 38 months.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT07129993
Study of Datopotamab Deruxtecan Plus Carboplatin or Cisplatin Versus Gemcitabine Plus Carboplatin or Cisplatin in Participants With Locally Advanced or Metastatic Urothelial Carcinoma
Recruiting
PHASE2Ages 18+InterventionalTreatmentDaiichi Sankyo
~630 participants
Updated 2026-08-20 on ClinicalTrials.gov
What's tested:Dato-DXdCarboplatinCisplatinGemcitabine
At a glance
Recruiting sites
29 of 100 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Overall Response Rate - Part A (Phase 2)
Measured over 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
+2 more outcomes measured
Conditions
Where it's being run
100 sites across 27 statesFrance27
Japan20
California6
Austria5
Germany4
Florida3
Illinois3
Tennessee3
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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)
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.
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.
Exclusion
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:
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):
Hypothyroidism/ hyperthyroidism
Type I diabetes
Hyperglycemia
Adrenal insufficiency
Adrenalitis c. Skin hypopigmentation (vitiligo)
What this trial measures
- Overall Response Rate - Part A (Phase 2)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)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)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.