Study BT8009-230 in Participants With Locally Advanced or Metastatic Urothelial Cancer (Duravelo-2)
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
- Metastatic Urothelial Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- 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
Arm | Description | Assigned Intervention |
---|---|---|
Experimental Cohort 1: BT8009 Arm 1 |
Participants will receive BT8009 and a standard dose of pembrolizumab. |
|
Experimental Cohort 1: BT8009 Arm 2 |
Participants will receive BT8009 and a standard dose of pembrolizumab. |
|
Active Comparator Cohort 1: Arm 3 |
Participants will receive Platinum-based combination chemotherapy +/- avelumab maintenance |
|
Experimental Cohort 2: BT8009 Arm 1 |
Participants will receive BT8009. |
|
Experimental Cohort 2: BT8009 Arm 2 |
Participants will receive BT8009. |
|
Experimental Cohort 2: Arm 3: BT8009 (Not Recruiting) |
Participants will receive BT8009 and a standard dose of pembrolizumab. |
|
Recruiting Locations
Little Rock 4119403, Arkansas 4099753 72205
Fullerton 5351247, California 5332921 92835
Orange 5379513, California 5332921 92868
San Francisco 5391959, California 5332921 94158
St. Helena 5390267, California 5332921 94574
Denver 5419384, Colorado 5417618 80218
New Haven 4839366, Connecticut 4831725 06520-8028
Newark 4143861, Delaware 4142224 19713
Jacksonville 4160021, Florida 4155751 32266
Miami 4164138, Florida 4155751 33136
Miami Beach 4164143, Florida 4155751 33140
Tampa 4174757, Florida 4155751 33612
Springfield 4250542, Illinois 4896861 62702
Des Moines 4853828, Iowa 4862182 50309
Westwood 4281639, Kansas 4273857 66205
Louisville 4299276, Kentucky 6254925 40202
Baton Rouge 4315588, Louisiana 4331987 70809
Omaha 5074472, Nebraska 5073708 68130
East Brunswick 5097402, New Jersey 5101760 08816
The Bronx 5110266, New York 5128638 10461
Charleston 4574324, South Carolina 4597040 29425
Myrtle Beach 4588718, South Carolina 4597040 29572
Nashville 4644585, Tennessee 4662168 37203
Fort Worth 4691930, Texas 4736286 76104
Houston 4699066, Texas 4736286 77030
San Antonio 4726206, Texas 4736286 78229
More Details
- NCT ID
- NCT06225596
- Status
- Recruiting
- Sponsor
- BicycleTx Limited