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

Conditions

• Bladder Cancer
• Urothelial Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Dato-DXd — DRUG
  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
• Carboplatin — DRUG
  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
• Cisplatin — DRUG
  Cisplatin will be administered as an intravenous (IV) infusion every three weeks (Q3W) at a dose of 70 mg/m2
• Gemcitabine — DRUG
  Gemcitabine will be administered as an IV infusion at a dose of 1000 mg/m2 on Day 1 and 8 of every 3 week cycle.

Study Details

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. 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.

Key Dates

Start date

Sep 26, 2025

Status verified

Jun 2026

Primary completion

Jun 1, 2029

Completion

Jan 22, 2030

Study Design

Enrollment

630 participants (estimated)

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Part A (Phase 2): Dato-DXd, 4 mg/kg with Platinum
  Participants will receive Dato-DXd in combination with platinum (carboplatin or cisplatin). The RP3D will be determined using data collected from Part A.
• Experimental: Part A (Phase 2): Dato-DXd, 6 mg/kg with Platinum
  Participants will receive Dato-DXd in combination with platinum (carboplatin or cisplatin). The RP3D will be determined using data collected from Part A.
• Experimental: Part B (Phase 3): Dato-DXd, RP3D with Platinum
  Participants will receive Dato-DXd at the RP3D in combination with platinum (carboplatin or cisplatin).
• Active Comparator: Part B (Phase 3): Gemcitabine with Platinum
  Participants will receive Gemcitabine in combination with platinum (carboplatin or cisplatin).

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 ]

Central Contacts

• Contact for Trial Information
  908-992-6400
  [email protected]

Locations (38)

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