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) ormetastatic UC of the renal pelvis, ureter, bladder, or urethra.

• Archival or fresh tumor tissue comprising muscle-invasive UC or locally advanced ormetastatic UC should be available for submission to central laboratory.

• Negative pregnancy test for women of childbearing potential (WOCBP) (negative serumtest at Screening and negative urine or serum test within 72 hours prior to thefirst 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 locallyadvanced or metastatic UC with the following exceptions:

1. Prior local intravesical chemotherapy, local surgery when full resection is notachieved, local immunotherapy, and radiotherapy are permitted if completed atleast 4 weeks prior to the initiation of study treatment and all acutetoxicities have resolved.

2. Prior neoadjuvant/adjuvant chemotherapy or monomethyl auristatin E (MMAE)-basedtherapy 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 systemictreatment for locally advanced or metastatic UC. This includes neoadjuvant/adjuvantplatinum-based chemotherapy if recurrence occurred within 12 months of completingtherapy.

• Cohort 2: Progression or recurrence of UC during or following receipt of most recenttherapy.

Key Exclusion Criteria:

• Active keratitis or corneal ulcerations.

• Requirement, while on study, for treatment with strong inhibitors or strong inducersof human cytochrome P450 3A (CYP3A) or inhibitors of P-glycoprotein (P-gp) includingherbal- or food-based inhibitors.

• Any condition requiring current treatment with high dose corticosteroids (> 10 mgdaily prednisone or equivalent).

• Known hypersensitivity or allergy to any of the ingredients of any of the studyinterventions, or to MMAE.

• Has not adequately recovered from recent major surgery (excluding placement ofvascular 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 chemotherapyregimen for locally advanced or metastatic UC. This includes neoadjuvant/adjuvantplatinum-based chemotherapy if recurrence occurred within 12 months of completingtherapy.

• Cohort 2: Prior treatment with enfortumab vedotin or any other MMAE-based therapy