Resumen

This is a global, multicenter, randomized, open-label study. The main objective of the study is to measure the clinical activity and safety of zelenectide pevedotin formally BT8009, in combination with pembrolizumab versus chemotherapy, and as monotherapy in participants with locally advanced or metastatic urothelial cancer (UC). The study includes a dose selection for zelenectide pevedotin and is comprised of 2 cohorts. Cohort 1 will include participants who have not received any prior systemic therapy for locally advanced or metastatic UC and are eligible to receive platinum-based chemotherapy, whereas Cohort 2 will include participants who have received ≥ 1 prior systemic therapy for locally advanced or metastatic UC.

Edad: 18 años o más

Género: Todos

Fecha de inicio: 01/24/2024

Fecha de finalización principal (estimada): 03/01/2028

Fecha estimada de finalización del estudio: 03/01/2028

Acepta voluntarios sanos: No

Propósito y descripción del ensayo

Criterios de elegibilidad

Edad: 18 años o más

Género: Todos

Acepta voluntarios sanos: No

Criterios clave de inclusión:

* Esperanza de vida ≥ 12 semanas.

* 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 primary 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.

Criterios de exclusión clave:

* Active keratitis or corneal ulcerations.

* Requirement, while receiving study medications, 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