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)

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Investigational drug late phase More information Moderate burden on patient More information No known activity More information

Trial Details

Sponsor: BicycleTx Limited (industry)

Phase: 2/3

Start date: Jan. 24, 2024

Planned enrollment: 956

Trial ID: NCT06225596
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More trial details at ClinicalTrials.gov More info

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chevron Show for: BT8009 (Zelenectide pevedotin, BCY8245)

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Goal: Evaluate the efficacy and safety of BT8009 (zelenectide pevedotin), a Nectin-4–targeting Bicycle Toxin Conjugate, as monotherapy and in combination with pembrolizumab versus standard platinum-based chemotherapy (with optional avelumab maintenance) in locally advanced or metastatic urothelial cancer, using an adaptive phase 2/3 design with dose selection followed by expansion.

Patients: Adults with histologically/cytologically confirmed, unresectable locally advanced or metastatic urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra, measurable disease by RECIST 1.1, and life expectancy ≥12 weeks. Cohort 1 includes previously untreated patients eligible for cisplatin- or carboplatin-based chemotherapy. Cohort 2 includes patients previously treated with ≥1 systemic regimen with progression/recurrence after the most recent therapy; prior enfortumab vedotin or other MMAE-based therapy is excluded in Cohort 2. Key exclusions include active corneal disease, need for strong CYP3A/P-gp modifiers, high-dose steroids, hypersensitivity to study components/MMAE, recent major surgery not recovered, and recent live vaccines.

Design: Global, multicenter, randomized, open-label, adaptive phase 2/3 trial with an initial dose-selection phase followed by continuation. Two parallel cohorts: first-line platinum-eligible and previously treated. Blinded independent central review is used for key efficacy endpoints.

Treatments: Cohort 1: BT8009 plus pembrolizumab (two experimental arms reflecting dose/schedule selection) versus standard platinum-based combination chemotherapy (gemcitabine with cisplatin or carboplatin) with optional avelumab maintenance per contemporary standard. Cohort 2: BT8009 monotherapy (two experimental arms reflecting dose/schedule selection); an earlier BT8009 plus pembrolizumab arm is not recruiting. BT8009 is a small-molecule Bicycle Toxin Conjugate targeting Nectin-4, linked to monomethyl auristatin E via a cleavable valine–citrulline linker. Its small size and short plasma half-life are designed to enhance tumor penetration and reduce normal tissue exposure compared with larger antibody–drug conjugates. Early phase 1/2 data in previously treated urothelial cancer reported an objective response rate of approximately 45% at the recommended phase 2 dose with a median duration of response around 11 months and a generally manageable safety profile characterized mainly by low-grade gastrointestinal and constitutional adverse events, with limited high-grade neuropathy, dermatologic, or ocular toxicity at the RP2D. Pembrolizumab and platinum-based chemotherapy with avelumab maintenance represent approved standard regimens in the studied settings.

Outcomes: Primary endpoints: Cohort 1 progression-free survival by BICR per RECIST 1.1; Cohort 2 objective response rate by BICR per RECIST 1.1. Key secondary endpoints across cohorts include ORR (BICR and investigator), PFS (BICR and investigator), duration of response, disease control rate, overall survival, safety (AEs/SAEs and laboratory, ECG, and vitals changes), and patient-reported outcomes (EQ-5D and EORTC QLQ-C30).

Burden on patient: Moderate. As a randomized phase 2/3 oncology study, patients should expect regular imaging for RECIST assessment, safety labs, vitals, and ECGs similar to standard of care. Additional requirements include provision of archival or fresh tumor tissue, which may necessitate a biopsy if archival tissue is inadequate. Combination arms involve intravenous administrations on standard schedules, implying frequent clinic visits. Although extensive pharmacokinetics sampling is not specified, early-phase dose selection components and ongoing safety monitoring may increase visit frequency early in treatment. Quality-of-life questionnaires add minor time. Overall, visit and monitoring intensity are greater than routine practice but typical for pivotal oncology trials.

Last updated: Oct 2025

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Jacksonville, Florida, 32266, United States

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Miami, Florida, 33165, United States

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Miami Beach, Florida, 33140, United States

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Miami, Florida, 33136, United States

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Springfield, Illinois, 62702, United States

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Des Moines, Iowa, 50309, United States

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Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, 70809, United States

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Corewell Health

Grand Rapids, Michigan, 49503, United States

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Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

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XCancer Omaha/Urology Cancer Center

Omaha, Nebraska, 68130, United States

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Summit Health (New Jersey Urology)

Voorhees Township, New Jersey, 01009, United States

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Astera Cancer Care

East Brunswick, New Jersey, 08816, United States

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Summit Health (New Jersey Urology)

Voorhees Township, New Jersey, 08043, United States

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Montefiore Medical Center

The Bronx, New York, 10461, United States

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Columbia University Irving Medical Center

New York, New York, 10032, United States

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University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

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Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

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Status: Recruiting

Medical University of South Carolina (MUSC) - Hollings Cancer Center

Charleston, South Carolina, 29425, United States

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SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

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University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

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The Center for Cancer and Blood Disorders

Fort Worth, Texas, 76104, United States

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MD Anderson Cancer Center

Houston, Texas, 77030, United States

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Status: Recruiting

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