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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Urothelial Cancer
• Intervention / Treatment: Drug: BT8009; Drug: Pembrolizumab; Drug: Gemcitabine + cisplatin Or carboplatin; Drug: Avelumab

• Study Type: Interventional
• Enrollment (Estimated): 956
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: BicycleTx Limited; Phone Number: 617-945-8155; Email: clinicalstudies@bicycletx.com

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Recruiting
      • Nebraska Cancer Specialists
    • Omaha, Nebraska, United States, 68130
      • Recruiting
      • XCancer Omaha/Urology Cancer Center
  • New Jersey
    • Voorhees, New Jersey, United States, 08043
      • Recruiting
      • Summit Health (New Jersey Urology)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: BT8009 Arm1; Participants will receive BT8009 and a standard dose of pembrolizumab.	Drug: BT8009; Participants will receive BT8009 IV on days 1, 8 +/- 15 schedule of every 21-day cycle.; Drug: 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.
Experimental: Cohort 1: BT8009 Arm 2; Participants will receive BT8009 and a standard dose of pembrolizumab.	Drug: BT8009; Participants will receive BT8009 IV on days 1, 8 +/- 15 schedule of every 21-day cycle.; Drug: 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.
Active Comparator: Cohort 1:Arm 3:Participants receiving Platinum-based combination chemotherapy + avelumab maintenance	Drug: 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.; Drug: 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.
Experimental: Cohort 2: BT8009 Arm 1; Participants will receive IV dose of BT8009.	Drug: BT8009; Participants will receive BT8009 IV on days 1, 8 +/- 15 schedule of every 21-day cycle.
Experimental: Cohort 2: BT8009 Arm 2; Participants will receive IV dose of BT8009.	Drug: BT8009; Participants will receive BT8009 IV on days 1, 8 +/- 15 schedule of every 21-day cycle.
Experimental: Cohort 2: Arm 3: BT8009 (Not Recruiting); Participants will receive BT8009 and a standard dose of pembrolizumab.	Drug: BT8009; Participants will receive BT8009 IV on days 1, 8 +/- 15 schedule of every 21-day cycle.; Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Cohorts 1 and 2: Overall survival (OS) rate	The time from randomization to date of death from any cause.	Up to approximately 7 years
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
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
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
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
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
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
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: Number of Participants with Clinically Significant Changes in Laboratory Results		Until the end of treatment, up to approximately 6 years
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: Number of Participants with Clinically Significant Changes in vital signs		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
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

Collaborators and Investigators

• Sponsor: BicycleTx Limited

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2024
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: January 12, 2024
• First Submitted That Met QC Criteria: January 24, 2024
• First Posted (Actual): January 26, 2024

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Bladder cancer; Avelumab; Pembrolizumab; Chemotherapy; Metastatic Urothelial Cancer; BT8009
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Carboplatin; Pembrolizumab; Avelumab; Gemcitabine
• Other Study ID Numbers: BT8009-230; 2023-504231-41 (EudraCT Number); U1111-1300-3791 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No