Study BT8009-230 in Participants With Locally Advanced or Metastatic Urothelial Cancer (Duravelo-2)

Metastatic Urothelial Cancer Clinical Trial

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)

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
• Start date: January 24, 2024
• Est. completion date: December 2030

Study information

• Verified date: May 2024
• Source: BicycleTx Limited
• Contact: BicycleTx Limited
• Phone: 617-945-8155
• Email: clinicalstudies[@]bicycletx.com
• Is FDA regulated: No
• 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 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

Related Conditions & MeSH terms

• Metastatic Urothelial Cancer

Intervention

Drug:
• BT8009
Participants will receive BT8009 IV 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
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

Country where clinical trial is conducted

United States, 

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