Dato-DXd plus Carboplatin or Cisplatin versus Gemcitabine plus Carboplatin or Cisplatin in Previously Treated la/mUC.

Trial details

Who runs it

Daiichi Sankyo Inc.

Trial code

EU 2024-516906-47-00

Record updated

2026. október 29.

Original description

Phase 2: • To evaluate the relative efficacy of Dato-DXd 4 mg/kg plus platinum therapy and Dato-DXd 6 mg/kg plus platinum therapy as measured by overall response rate (ORR) by investigator.Read full original descriptionShow less

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).

Phase 2: • To evaluate the relative efficacy of Dato-DXd 4 mg/kg plus platinum therapy and Dato-DXd 6 mg/kg plus platinum therapy as measured by overall response rate (ORR) by investigator.

Phase 3: • To compare the efficacy of Dato-DXd plus platinum therapy with gemcitabine plus platinum therapy as measured by progression-free survival (PFS) by Blinded Independent Central Review (BICR). • To compare the efficacy of Dato-DXd plus platinum therapy with gemcitabine plus platinum therapy as measured by overall survival (OS).

Inclusion: Adult ≥18 years at the time the ICF is signed; Histologically or cytologically confirmed unresectable locally advanced or metastatic urothelial carcinoma of the bladder, renal pelvis, ureter, or urethra; Must provide tumor tissue sample from archival tissue or newly obtained pretreatment biopsy for exploratory biomarker testing; Participant must be considered eligible to receive cisplatin- or carboplatin-containing chemotherapy, in the investigator’s judgment; Must have experienced radiographic progression or relapse during or after 1L of enfortumab vedotin (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. Participants 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; Measurable disease on CT/MRI per RECIST version 1.1 as assessed by investigator; ECOG PS of 0 or 1; Has required baseline laboratory data: adequate bone marrow function, adequate renal function, adequate hepatic function, and adequate blood clotting function.

Exclusion: Has had prior systemic therapy other than the combination of EV and pembrolizumab for la/mUC; Has had treatment with any of the following: History of an allogeneic bone marrow or solid organ transplant, concomitant treatment with any prohibited medications in the protocol, prior TROP2 directed ADC therapy; Has toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet improved to NCI-CTCAE version 5.0 Grade ≤1 or baseline. Participants may be enrolled with chronic, stable Grade 2 toxicities which the investigator deems related to previous anticancer therapy; Uncontrolled or significant cardiovascular disease; 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; History of severe hypersensitivity to either the drug or inactive ingredients of Dato-DXd, platinum (i.e., both carboplatin and cisplatin), or gemcitabine; Has an uncontrolled infection requiring systemic therapy; Has clinically significant corneal disease.

EU CTIS 2024-516906-47-00