OncoMatch/Clinical Trials/NCT07129993
Study of Datopotamab Deruxtecan Plus Carboplatin or Cisplatin Versus Gemcitabine Plus Carboplatin or Cisplatin in Participants With Locally Advanced or Metastatic Urothelial Carcinoma
Is NCT07129993 recruiting? Yes, currently enrolling (May 2026). This Phase 2/3 trial studies multiple treatments including Dato-DXd and Carboplatin for urothelial cancer.
Treatment: Dato-DXd · Carboplatin · Cisplatin · Gemcitabine — 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.
Check if I qualifyExtracted eligibility criteria
Cancer type
Urothelial Carcinoma
Biomarker criteria
Excluded: TACSTD2 prior TROP2 directed ADC therapy
Prior TROP2 directed ADC therapy
Disease stage
Required: Stage T4B, ANY N, ANY T, N2-3, ANY T, ANY N, M1
unresectable locally advanced (T4b, any N; or any T, N 2-3) or metastatic (any T, any N, M1) urothelial carcinoma
Prior therapy
Must have received: antibody-drug conjugate (enfortumab vedotin) — first-line
Must have experienced radiographic progression or relapse during or after 1L of EV and pembrolizumab. Participant who discontinued EV and pembrolizumab 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 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.
Must have received: anti-PD-1 therapy (pembrolizumab) — first-line
Must have experienced radiographic progression or relapse during or after 1L of EV and pembrolizumab. Participant who discontinued EV and pembrolizumab 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 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.
Cannot have received: systemic therapy
Exception: combination of EV and pembrolizumab for la/mUC; or anti-Nectin 4 or vedotin payload (MMAE or other microtubule inhibitors) combined with PD1/PD-L1 inhibitors in 1L la/mUC (with sponsor approval)
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.
Lab requirements
Kidney function
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 may be considered cisplatin-eligible based on the investigator's clinical judgment
Cardiac function
NCI-CTCAE Grade ≥2 audiometric hearing loss; NCI-CTCAE Grade ≥2 peripheral neuropathy; NYHA Class III or IV heart failure; QTcF interval >450 ms; myocardial infarction within 6 months prior to randomization; uncontrolled angina pectoris within 6 months prior to randomization; 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)
Participants are cisplatin-ineligible if they meet any of the following criteria: GFR <60 mL/min... NCI-CTCAE Grade ≥2 audiometric hearing loss... NCI-CTCAE Grade ≥2 peripheral neuropathy... NYHA Class III heart failure... QTcF interval >450 ms... myocardial infarction within 6 months prior to randomization... uncontrolled angina pectoris within 6 months prior to randomization... 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)
Structured fields extracted by AI. May contain errors — verify against the official protocol.
US trial sites
- Research Site · Fullerton, California
- Research Site · La Jolla, California
- Research Site · San Francisco, California
- Research Site · Aurora, Colorado
- Research Site · Orange City, Florida
Showing up to 5 US sites. See all sites on ClinicalTrials.gov →
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