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Purpose

This is a global, multicenter, randomized, open-label study, with an adaptive design. The main objective of the study is to measure the efficacy and safety of BT8009 (zelenectide pevedotin) as monotherapy and in combination with pembrolizumab in participants with locally advanced or metastatic urothelial cancer (UC). The study includes a dose selection phase followed by an adaptive design continuation. The study 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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

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

Study Design

Phase
Phase 2/Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Cohort 1: BT8009 Arm 1 		Participants will receive BT8009 and a standard dose of pembrolizumab.
  • Drug: BT8009
    Participants will receive BT8009 on Days 1, 8, and 15 of every 21-day cycle.
  • Drug: Pembrolizumab
    Participants will receive Pembrolizumab on Day 1 of every 21-day cycle. Pembrolizumab infusion will be started 30 minutes following the completion of the BT8009 infusion.
Experimental
Cohort 1: BT8009 Arm 2 		Participants will receive BT8009 and a standard dose of pembrolizumab.
  • Drug: BT8009
    Participants will receive BT8009 on Days 1 and 8 of every 21-day cycle.
  • Drug: Pembrolizumab
    Participants will receive Pembrolizumab on Day 1 of every 21-day cycle. Pembrolizumab infusion will be started 30 minutes following the completion of the BT8009 infusion.
Active Comparator
Cohort 1: Arm 3 		Participants will receive Platinum-based combination chemotherapy +/- avelumab maintenance
  • Drug: Gemcitabine + cisplatin Or carboplatin
    Participants will receive Gemcitabine on Days 1 and 8 of every 21-day cycle plus cisplatin Or carboplatin on Day 1 of every 21-day cycle.
  • Drug: Avelumab
    After 4-6 cycles of Gemcitabine + Cisplatin or Carboplatin participants will receive maintenance Avelumab, if clinically indicated, on Days 1 and 15 each 28-day cycle.
Experimental
Cohort 2: BT8009 Arm 1 		Participants will receive BT8009.
  • Drug: BT8009
    Participants will receive BT8009 on Days 1, 8, and 15 of every 21-day cycle.
Experimental
Cohort 2: BT8009 Arm 2 		Participants will receive BT8009.
  • Drug: BT8009
    Participants will receive BT8009 on Days 1 and 8 of every 21-day cycle.
Experimental
Cohort 2: Arm 3: BT8009 (Not Recruiting) 		Participants will receive BT8009 and a standard dose of pembrolizumab.
  • Drug: BT8009
    Participants will receive BT8009 on days 1, 8 +/- 15 schedule of every 21-day cycle.
  • Drug: Pembrolizumab
    Participants will receive Pembrolizumab on Day 1 of every 21-day cycle. Pembrolizumab infusion will be started 30 minutes following the completion of the BT8009 infusion.

Recruiting Locations

University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205

Virginia K. Crosson Cancer Center at St. Jude Medical Center
Fullerton, California 92835

University of California - Irvine Medical Center
Orange, California 92868

Adventist Health St. Helena
Saint Helena, California 94574

University of California, San Francisco (UCSF)
San Francisco, California 94158

Rocky Mountain Cancer Center
Denver, Colorado 80218

Yale University School of Medicine - Yale Cancer Center
New Haven, Connecticut 06520-8028

Medical Oncology Hematology Consultants
Newark, Delaware 19713

Cancer Specialists of North Florida
Jacksonville, Florida 32266

Mount Sinai Medical Center of Florida, Inc.
Miami Beach, Florida 33140

University of Miami - Sylvester Comprehensive Cancer Center
Miami, Florida 33136

Southern Illinois University (SIU) - Simmons Cancer Institute
Springfield, Illinois 62702

Mission Cancer + Blood
Des Moines, Iowa 50309

University of Kansas Cancer Center
Westwood, Kansas 66205

UofL Health Brown Cancer Center
Louisville, Kentucky 40202

Mary Bird Perkins Cancer Center
Baton Rouge, Louisiana 70809

Princess Margaret Hospital
Grand Rapids, Michigan 49503

Nebraska Cancer Specialists
Omaha, Nebraska 68130

XCancer Omaha/Urology Cancer Center
Omaha, Nebraska 68130

Astera Cancer Care
East Brunswick, New Jersey 08816

Montefiore Medical Center
Bronx, New York 10461

Columbia University Irving Medical Center
New York, New York 10032

University Hospitals Cleveland Medical Center
Cleveland, Ohio 44106

Medical University of South Carolina (MUSC) - Hollings Cancer Center
Charleston, South Carolina 29425

Carolina Urologic Research Center
Myrtle Beach, South Carolina 29572

SCRI Oncology Partners
Nashville, Tennessee 37203

The Center for Cancer and Blood Disorders
Fort Worth, Texas 76104

MD Anderson Cancer Center
Houston, Texas 77030

More Details

NCT ID
NCT06225596
Status
Recruiting
Sponsor
BicycleTx Limited

Study Contact

BicycleTx Limited
617-945-8155
clinicalstudies@bicycletx.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.