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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT06225596
Other study ID # BT8009-230
Secondary ID 2023-504231-41U1
Status Recruiting
Phase Phase 2/Phase 3
First received
Last updated
Start date January 24, 2024
Est. completion date December 2030

Study information

Verified date June 2024
Source BicycleTx Limited
Contact BicycleTx Limited
Phone 617-945-8155
Email clinicalstudies@bicycletx.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Recruiting
Enrollment 956
Est. completion date December 2030
Est. primary completion date December 2030
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
BT8009
Participants will receive BT8009 on Days 1, 8, and 15 of every 21-day cycle.
BT8009
Participants will receive BT8009 on Days 1 and 8 of every 21-day cycle.
BT8009
Participants will receive BT8009 on days 1, 8 +/- 15 schedule of every 21-day cycle.
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.
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.
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.

Locations

Country Name City State
Australia Cancer Research SA Adelaide
Australia Calvary Mater Newcastle Hunter
Australia Icon Cancer Centre South Brisbane
Georgia Multiprofile Clinic Consilium Medulla LTD Tbilisi
Georgia New Vision University Hospital Tbilisi
Georgia The First University Clinic of Tbilisi State Medical University Tbilisi
United States Mount Sinai Medical Center of Florida, Inc. Miami Beach Florida
United States Carolina Urologic Research Center Myrtle Beach South Carolina
United States Nebraska Cancer Specialists Omaha Nebraska
United States XCancer Omaha/Urology Cancer Center Omaha Nebraska
United States Summit Health (New Jersey Urology) Voorhees New Jersey

Sponsors (1)

Lead Sponsor Collaborator
BicycleTx Limited

Countries where clinical trial is conducted

United States,  Australia,  Georgia, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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) The time from randomization to date of first documentation of disease progression or death. Up to approximately 6 years
Primary Cohort 2: Objective response rate (ORR) per RECIST 1.1 assessed by BICR The time from randomization to date of first documentation of disease progression or death. Up to approximately 6 years
Secondary Cohort 1: ORR per RECIST 1.1 assessed by BICR The time from randomization to date of first documentation of disease progression or death. Up to approximately 6 years
Secondary Cohorts 1 and 2: ORR per RECIST 1.1 assessed by Investigator The time from randomization to date of first documentation of disease progression or death. Up to approximately 6 years
Secondary Cohorts 1 and 2: Overall survival (OS) rate The time from randomization to date of death from any cause. Up to approximately 7 years
Secondary Cohorts 1 and 2: Duration of response (DoR) per RECIST 1.1 assessed by BICR 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. Up to approximately 6 years
Secondary Cohorts 1 and 2: DoR per RECIST 1.1 assessed by Investigator 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. Up to approximately 6 years
Secondary Cohorts 1 and 2: Disease control rate (DCR) per RECIST 1.1 assessed by BICR The time from randomization to date of first documentation of disease progression or death. Up to approximately 6 years
Secondary Cohorts 1 and 2: DCR per RECIST 1.1 assessed by Investigator The time from Cycle 1 Day 1 to date of first documentation of disease progression or death Up to approximately 6 years
Secondary Cohorts 1 and 2: PFS per RECIST v1.1 assessed by Investigator The time from randomization to date of first documentation of disease progression or death. Up to approximately 6 years
Secondary Cohort 2: PFS per RECIST v1.1 assessed by BICR The time from randomization to date of first documentation of disease progression or death. Up to approximately 6 years
Secondary 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
Secondary Cohorts 1 and 2: Number of Participants with Clinically Significant Changes in Laboratory Results Until the end of treatment, up to approximately 6 years
Secondary Cohorts 1 and 2: Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Until the end of treatment, up to approximately 6 years
Secondary Cohorts 1 and 2: Number of Participants with Clinically Significant Changes in vital signs Until the end of treatment, up to approximately 6 years
Secondary Cohorts 1 and 2: Change from Baseline in Euroqol-5 Dimensions (EQ-5D) Questionnaire Until the end of treatment, up to approximately 6 years
Secondary 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
See also
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Completed NCT02826564 - Trial of Stereotactic Body Radiotherapy With Concurrent Pembrolizumab in Metastatic Urothelial Cancer Phase 1
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Not yet recruiting NCT05390645 - A Study of MFA-370 in Patients With Metastatic Urothelial Cancer Phase 1/Phase 2
Recruiting NCT03745911 - Paclitaxel and TAK-228 in Urothelial Carcinoma Phase 2
Completed NCT03390595 - Avelumab Plus Carboplatin-gemcitabine in Urothelial Carcinoma Phase 2
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Active, not recruiting NCT04995419 - A Study to Evaluate Enfortumab Vedotin (ASG-22CE) in Chinese Participants With Locally Advanced or Metastatic Urothelial Cancer Who Previously Received Platinum-containing Chemotherapy and Programmed Cell Death Protein-1 ( PD 1) / (Programmed Death Ligand-1 (PD-L1) Inhibitor Therapy Phase 2
Completed NCT03679767 - A Study of INCMGA00012 in Participants With Selected Solid Tumors (POD1UM-203) Phase 2
Completed NCT02240017 - A Study Evaluating Chemotherapy With Fractionated Cisplatin/Gemcitabine Versus Carboplatin/Gemcitabine in the Treatment of Advanced or Metastatic Urothelial Cancer With Impaired Renal Function. Phase 2/Phase 3
Recruiting NCT03547973 - Study of Sacituzumab Govitecan in Participants With Urothelial Cancer That Cannot Be Removed or Has Spread Phase 2
Completed NCT03070990 - A Study of Enfortumab Vedotin in Japanese Subjects With Locally Advanced or Metastatic Urothelial Carcinoma Phase 1
Completed NCT03448718 - Trial of Olaparib in Patients With Metastatic Urothelial Cancer Harboring DNA Damage Response Gene Alterations Phase 2