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.
Brief Title
Study BT8009-230 in Participants With Locally Advanced or Metastatic Urothelial Cancer (Duravelo-2)
Central Contacts
Central Contact Role
Contact
Central Contact Phone
617-945-8155
Central Contact Email
clinicalstudies@bicycletx.com
Completion Date
Completion Date Type
Estimated
Conditions
Metastatic Urothelial Cancer
Eligibility Criteria
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
* 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
Inclusion Criteria
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.
* 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.
Gender
All
Gender Based
false
Keywords
Metastatic Urothelial Cancer
BT8009
Bladder cancer
Pembrolizumab
Chemotherapy
Avelumab
Zelenectide pevedotin
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT06225596
Org Class
Industry
Org Full Name
BicycleTx Limited
Org Study Id
BT8009-230
Overall Status
Recruiting
Phases
Phase 2
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Randomized Open-Label Phase 2/3 Study of BT8009 as Monotherapy or in Combination in Participants With Locally Advanced or Metastatic Urothelial Cancer (Duravelo-2)
Primary Outcomes
Outcome Description
The time from randomization to date of first documentation of disease progression or death.
Outcome Measure
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)
Outcome Time Frame
Up to approximately 6 years
Outcome Description
The time from randomization to date of first documentation of disease progression or death.
Outcome Measure
Cohort 2: Objective response rate (ORR) per RECIST 1.1 assessed by BICR
Outcome Time Frame
Up to approximately 6 years
Secondary Ids
Secondary Id
2023-504231-41
Secondary Id
U1111-1300-3791
Secondary Outcomes
Outcome Description
The time from randomization to date of first documentation of disease progression or death.
Outcome Time Frame
Up to approximately 6 years
Outcome Measure
Cohort 1: ORR per RECIST 1.1 assessed by BICR
Outcome Description
The time from randomization to date of first documentation of disease progression or death.
Outcome Time Frame
Up to approximately 6 years
Outcome Measure
Cohorts 1 and 2: ORR per RECIST 1.1 assessed by Investigator
Outcome Description
The time from randomization to date of death from any cause.
Outcome Time Frame
Up to approximately 7 years
Outcome Measure
Cohorts 1 and 2: Overall survival (OS) rate
Outcome Description
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.
Outcome Time Frame
Up to approximately 6 years
Outcome Measure
Cohorts 1 and 2: Duration of response (DoR) per RECIST 1.1 assessed by BICR
Outcome Description
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.
Outcome Time Frame
Up to approximately 6 years
Outcome Measure
Cohorts 1 and 2: DoR per RECIST 1.1 assessed by Investigator
Outcome Description
The time from randomization to date of first documentation of disease progression or death.
Outcome Time Frame
Up to approximately 6 years
Outcome Measure
Cohorts 1 and 2: Disease control rate (DCR) per RECIST 1.1 assessed by BICR
Outcome Description
The time from Cycle 1 Day 1 to date of first documentation of disease progression or death
Outcome Time Frame
Up to approximately 6 years
Outcome Measure
Cohorts 1 and 2: DCR per RECIST 1.1 assessed by Investigator
Outcome Description
The time from randomization to date of first documentation of disease progression or death.
Outcome Time Frame
Up to approximately 6 years
Outcome Measure
Cohorts 1 and 2: PFS per RECIST v1.1 assessed by Investigator
Outcome Description
The time from randomization to date of first documentation of disease progression or death.
Outcome Time Frame
Up to approximately 6 years
Outcome Measure
Cohort 2: PFS per RECIST v1.1 assessed by BICR
Outcome Time Frame
Until 30 days post last dose, up to approximately 6 years
Outcome Measure
Cohorts 1 and 2: Number of participants reporting adverse events (AEs) and Serious adverse events (SAEs)
Outcome Time Frame
Until the end of treatment, up to approximately 6 years
Outcome Measure
Cohorts 1 and 2: Number of Participants with Clinically Significant Changes in Laboratory Results
Outcome Time Frame
Until the end of treatment, up to approximately 6 years
Outcome Measure
Cohorts 1 and 2: Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG)
Outcome Time Frame
Until the end of treatment, up to approximately 6 years
Outcome Measure
Cohorts 1 and 2: Number of Participants with Clinically Significant Changes in vital signs
Outcome Time Frame
Until the end of treatment, up to approximately 6 years
Outcome Measure
Cohorts 1 and 2: Change from Baseline in Euroqol-5 Dimensions (EQ-5D) Questionnaire
Outcome Time Frame
Until the end of treatment, up to approximately 6 years
Outcome Measure
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)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Locked Fields
Render the field
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Benjamin Gartrell
Investigator Email
bgartrel@montefiore.org
Investigator Phone
718-405-8404