Study BT8009-230 in Participants With Locally Advanced or Metastatic Urothelial Cancer (Duravelo-2)
- Conditions
- Metastatic Urothelial Cancer
- Interventions
- Registration Number
- NCT06225596
- Lead Sponsor
- BicycleTx Limited
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 956
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Life expectancy ≥ 12 weeks.
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Measurable disease as defined by RECIST v1.1.
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Histologically or cytologically confirmed locally advanced (unresectable) or metastatic UC of the renal pelvis, ureter, bladder, or urethra.
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Archival or fresh tumor tissue comprising muscle-invasive UC or locally advanced or metastatic UC should be available for submission to central laboratory.
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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).
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Cohort 1: Previously Untreated: Eligible to receive platinum-based chemotherapy (either cisplatin- or carboplatin-based chemotherapy based on Investigator decision.
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Cohort 1: Participants must not have received prior systemic therapy for locally advanced or metastatic UC with the following exceptions:
- 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.
- Prior neoadjuvant/adjuvant chemotherapy or monomethyl auristatin E (MMAE)-based therapy with recurrence >12 months from completion of therapy.
- Prior neoadjuvant/adjuvant immune checkpoint inhibitor therapy with recurrence >12 months from completion of therapy.
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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.
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Cohort 2: Progression or recurrence of UC during or following receipt of most recent therapy.
Key
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1: BT8009 Arm 1 Pembrolizumab Participants will receive BT8009 and a standard dose of pembrolizumab. Cohort 1: BT8009 Arm 1 BT8009 Participants will receive BT8009 and a standard dose of pembrolizumab. Cohort 2: BT8009 Arm 1 BT8009 Participants will receive BT8009. Cohort 1: Arm 3 Gemcitabine + cisplatin Or carboplatin Participants will receive Platinum-based combination chemotherapy +/- avelumab maintenance Cohort 1: BT8009 Arm 2 BT8009 Participants will receive BT8009 and a standard dose of pembrolizumab. Cohort 2: BT8009 Arm 2 BT8009 Participants will receive BT8009. Cohort 2: Arm 3: BT8009 (Not Recruiting) BT8009 Participants will receive BT8009 and a standard dose of pembrolizumab. Cohort 1: BT8009 Arm 2 Pembrolizumab Participants will receive BT8009 and a standard dose of pembrolizumab. Cohort 2: Arm 3: BT8009 (Not Recruiting) Pembrolizumab Participants will receive BT8009 and a standard dose of pembrolizumab. Cohort 1: Arm 3 Avelumab Participants will receive Platinum-based combination chemotherapy +/- avelumab maintenance
- Primary Outcome Measures
Name Time Method Cohort 1: Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) assessed by blinded central independent review (BICR) Up to approximately 6 years The time from randomization to date of first documentation of disease progression or death.
Cohort 2: Objective response rate (ORR) per RECIST 1.1 assessed by BICR Up to approximately 6 years The time from randomization to date of first documentation of disease progression or death.
- Secondary Outcome Measures
Name Time Method Cohorts 1 and 2: Number of Participants with Clinically Significant Changes in Laboratory Results Until the end of treatment, up to approximately 6 years Cohort 2: PFS per RECIST v1.1 assessed by BICR Up to approximately 6 years The time from randomization to date of first documentation of disease progression or death.
Cohorts 1 and 2: Number of participants reporting adverse events (AEs) and Serious adverse events (SAEs) Until 30 days post last dose, up to approximately 6 years Cohorts 1 and 2: DCR per RECIST 1.1 assessed by Investigator Up to approximately 6 years The time from Cycle 1 Day 1 to date of first documentation of disease progression or death
Cohorts 1 and 2: PFS per RECIST v1.1 assessed by Investigator Up to approximately 6 years The time from randomization to date of first documentation of disease progression or death.
Cohorts 1 and 2: ORR per RECIST 1.1 assessed by Investigator Up to approximately 6 years The time from randomization to date of first documentation of disease progression or death.
Cohorts 1 and 2: Overall survival (OS) rate Up to approximately 7 years The time from randomization to date of death from any cause.
Cohorts 1 and 2: Duration of response (DoR) per RECIST 1.1 assessed by BICR Up to approximately 6 years The time from time of first documentation of objective response that is subsequently confirmed to date of first documentation of objective tumor progression or death.
Cohorts 1 and 2: DoR per RECIST 1.1 assessed by Investigator Up to approximately 6 years The time from time of first documentation of objective response that is subsequently confirmed to date of first documentation of objective tumor progression or death.
Cohorts 1 and 2: Number of Participants with Clinically Significant Changes in vital signs Until the end of treatment, up to approximately 6 years Cohort 1: ORR per RECIST 1.1 assessed by BICR Up to approximately 6 years The time from randomization to date of first documentation of disease progression or death.
Cohorts 1 and 2: Disease control rate (DCR) per RECIST 1.1 assessed by BICR Up to approximately 6 years The time from randomization to date of first documentation of disease progression or death.
Cohorts 1 and 2: Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Until the end of treatment, up to approximately 6 years Cohorts 1 and 2: Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Until the end of treatment, up to approximately 6 years Cohorts 1 and 2: Change from Baseline in Euroqol-5 Dimensions (EQ-5D) Questionnaire Until the end of treatment, up to approximately 6 years
Related Research Topics
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Trial Locations
- Locations (169)
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Virginia K. Crosson Cancer Center at St. Jude Medical Center
🇺🇸Fullerton, California, United States
University of California - Irvine Medical Center
🇺🇸Orange, California, United States
Adventist Health St. Helena
🇺🇸Saint Helena, California, United States
University of California, San Francisco (UCSF)
🇺🇸San Francisco, California, United States
Rocky Mountain Cancer Center
🇺🇸Denver, Colorado, United States
Yale University School of Medicine - Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Medical Oncology Hematology Consultants
🇺🇸Newark, Delaware, United States
Cancer Specialists of North Florida
🇺🇸Jacksonville, Florida, United States
Mount Sinai Medical Center of Florida, Inc.
🇺🇸Miami Beach, Florida, United States
Scroll for more (159 remaining)University of Arkansas for Medical Sciences🇺🇸Little Rock, Arkansas, United States