Study BT8009-230 in Participants With Locally Advanced or Metastatic Urothelial Cancer (Duravelo-2)

Key Inclusion Criteria: * Life expectancy ≥ 12 weeks. * Measurable disease as defined by RECIST v1.1. * Histologically or cytologically confirmed locally advanced (unresectable) or metastatic UC of the renal pelvis, ureter, bladder, or urethra. * Archival or fresh tumor tissue comprising muscle-invasive UC or locally advanced or metastatic UC should be available for submission to central laboratory. * Negative pregnancy test for women of childbearing potential (WOCBP) (negative serum test at Screening and negative urine or serum test within 72 hours prior to the first dose). * Cohort 1: Previously Untreated: Eligible to receive platinum-based chemotherapy (either cisplatin- or carboplatin-based chemotherapy based on Investigator decision. * Cohort 1: Participants must not have received prior systemic therapy for locally advanced or metastatic UC with the following exceptions: 1. Prior local intravesical chemotherapy, local surgery when full resection is not achieved, local immunotherapy, and radiotherapy are permitted if completed at least 4 weeks prior to the initiation of study treatment and all acute toxicities have resolved. 2. Prior neoadjuvant/adjuvant chemotherapy or monomethyl auristatin E (MMAE)-based therapy with recurrence \>12 months from completion of therapy. 3. Prior neoadjuvant/adjuvant immune checkpoint inhibitor therapy with recurrence \>12 months from completion of therapy. * Cohort 2: Previously Treated: Participants must have received ≥ 1 prior systemic treatment for locally advanced or metastatic UC. This includes neoadjuvant/adjuvant platinum-based chemotherapy if recurrence occurred within 12 months of completing therapy. * Cohort 2: Progression or recurrence of UC during or following receipt of most recent therapy. Key Exclusion Criteria: * Active keratitis or corneal ulcerations. * Requirement, while on study, for treatment with strong inhibitors or strong inducers of human cytochrome P450 3A (CYP3A) or inhibitors of P-glycoprotein (P-gp) including herbal- or food-based inhibitors. * Any condition requiring current treatment with high dose corticosteroids (\> 10 mg daily prednisone or equivalent). * Known hypersensitivity or allergy to any of the ingredients of any of the study interventions, or to MMAE. * Has not adequately recovered from recent major surgery (excluding placement of vascular access). * Receipt of live or attenuated vaccine within 30 days of first dose. * Cohort 1: Previously Untreated: Prior treatment with a checkpoint inhibitor (CPI) for any other malignancy within the last 12 months. * Cohort 2: Previously Treated: Received more than 1 prior platinum-based chemotherapy regimen for locally advanced or metastatic UC. This includes neoadjuvant/adjuvant platinum-based chemotherapy if recurrence occurred within 12 months of completing therapy. * Cohort 2: Prior treatment with enfortumab vedotin or any other MMAE-based therapy