Dato-DXd with Platinum Drugs Compared to Gemcitabine with Platinum in Urothelial Cancer

Who can take part

• 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

Who cannot take part

• 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