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

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Cohort 1: Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors

Primary Outcome 1 - Timeframe: Up to approximately 6 years

Primary Outcome 2 - Measure: version 1.1 (RECIST v1.1) assessed by blinded central independent review (BICR)

Primary Outcome 2 - Timeframe: Up to approximately 6 years

Primary Outcome 3 - Measure: Cohort 2: Objective response rate (ORR) per RECIST 1.1 assessed by BICR

Primary Outcome 3 - Timeframe: N/A

CONDITION

• Metastatic Urothelial Cancer

ELIGIBILITY

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: N/A

Role: N/A

Affiliation: N/A

Overall Contact

Name: BicycleTx Limited

Phone: 617-945-8155

Email: [email protected]

LOCATION