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

NCT06225596
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Phase
Phase 2
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Recruitment status
Active, not recruiting
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Participants
375
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Lead sponsor
BicycleTx Limited
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Start date
2024-01-24
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Number of sites
102
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Summary
This is a global, multicenter, randomized, open-label study. The main objective of the study is to measure the clinical activity and safety of zelenectide pevedotin formally BT8009, in combination with pembrolizumab versus chemotherapy, and as monotherapy in participants with locally advanced or metastatic urothelial cancer (UC). The study includes a dose selection for zelenectide pevedotin and 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.
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Short title
Study BT8009-230 in Participants With Locally Advanced or Metastatic Urothelial Cancer (Duravelo-2)
clinicaltrials.gov
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)
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Control arm
Active comparator
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Active, not recruiting
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Phase
Phase 2
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Study type
Interventional
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Completion date
2028-03-01
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First posted
2024-01-26
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Registry last updated
2026-05-27
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Primary completion date
2028-03-01
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Start date
2024-01-24
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Participants
375
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Participant count basis
Estimated
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Planned participants
375
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Protocol amendments
3
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Number of sites
102
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
BicycleTx Limited
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06225596
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ClinicalTrials.gov ID
NCT06225596
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Registry record
Open registry record
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Allocation
Randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Cohort 1: Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1(RECIST v1.1) by blinded central independent review (BICR) of optimal dose zelenectide pevedotin with pembrolizumab versus chemotherapy

    Timeframe: Up to approximately 4 years

    The time from randomization to date of first documentation of disease progression or death.

  2. Cohort 2: PFS per RECIST v1.1 assessed by BICR of zelenectide pevedotin monotherapy in each treatment regimen

    Timeframe: Up to approximately 4 years

    The time from randomization to date of first documentation of disease progression or death.

  3. Cohort 2: Objective response rate (ORR) per RECIST v1.1 assessed by BICR of zelenectide pevedotin monotherapy in each treatment regimen

    Timeframe: Up to approximately 4 years

  1. Cohort 1: PFS per RECIST v1.1 assessed by BICR of zelenectide pevedotin combined treatment arms versus chemotherapy

    Timeframe: Up to approximately 4 years

    The time from randomization to date of first documentation of disease progression or death.

  2. Cohort 1: ORR per RECIST v1.1 assessed by BICR of optimal dose zelenectide pevedotin in combination with pembrolizumab versus chemotherapy.

    Timeframe: Up to approximately 4 years

  3. Cohort 1: ORR per RECIST v1.1 assessed by BICR of zelenectide pevedotin combined treatment arms versus chemotherapy

    Timeframe: Up to approximately 4 years

  4. Cohort 1: Overall survival (OS) rate of optimal dose zelenectide pevedotin in combination with pembrolizumab versus chemotherapy

    Timeframe: Up to approximately 4 years

    The time from randomization to date of death from any cause.

  5. Cohort 1: Duration of response (DoR) per RECIST v1.1 assessed by BICR of optimal dose of zelenectide pevedotin in combination with pembrolizumab

    Timeframe: Up to approximately 4 years

    The time from time of first documentation of objective response that is subsequently confirmed to date of first documentation of disease progression or death.

  6. Cohort 1: Disease control rate (DCR) per RECIST v1.1 assessed by BICR of optimal dose of zelenectide pevedotin in combination with pembrolizumab

    Timeframe: Up to approximately 4 years

    The time from randomization to date of first documentation of disease progression or death.

  7. Cohort 1: PFS per RECIST v1.1 assessed by BICR of unselected zelenectide pevedotin dose in combination with pembrolizumab

    Timeframe: Up to approximately 4 years

    The time from randomization to date of first documentation of disease progression or death.

  8. Cohort 1: OS rate of zelenectide pevedotin combined treatment arms in combination with pembrolizumab versus chemotherapy

    Timeframe: Up to approximately 4 years

    The time from randomization to date of death from any cause

  9. Cohort 2: DoR per RECIST v1.1 assessed by BICR in each treatment regimen

    Timeframe: Up to approximately 4 years

    The time from time of first documentation of objective response that is subsequently confirmed to date of first documentation of disease progression or death.

  10. Cohort 2: DCR per RECIST v1.1 assessed by BICR in each treatment regimen

    Timeframe: Up to approximately 4 years

    The time from cycle 1 Day 1 to date of first documentation of disease progression or death

  11. Cohort 2: OS rate in each treatment regimen

    Timeframe: Up to approximately 4 years

    The time from randomization to date of death from any cause

  12. Cohorts 1 and 2: Safety and tolerability of each treatment regimen

    Timeframe: Until 30 days post last dose, up to approximately 4 years

    Safety will be reported as incidence, severity, seriousness, relationship to study and types of adverse events

  13. Cohorts 1 and 2: Exposure-efficacy relationships for zelenectide pevedotin area under the plasma concentration-time curve (AUC)

    Timeframe: Until the end of treatment, up to approximately 4 years

    Quantitative modeling of the association between measured zelenectide pevedotin pharmacokinetic (PK) parameter (AUC) and ORR.

  14. Cohorts 1 and 2: Exposure-efficacy relationships for zelenectide pevedotin AUC

    Timeframe: Until the end of treatment, up to approximately 4 years

    Quantitative modeling of the association between measured zelenectide pevedotin PK parameter (AUC) and PFS.

  15. Cohorts 1 and 2: Exposure-efficacy relationships for monomethyl auristatin (MMAE) AUC

    Timeframe: Until the end of treatment, up to approximately 4 years

    Quantitative modeling of the association between measured MMAE PK parameter (AUC) and ORR.

  16. Cohorts 1 and 2: Exposure-efficacy relationships for MMAE AUC

    Timeframe: Until the end of treatment, up to approximately 4 years

    Quantitative modeling of the association between measured MMAE PK parameter (AUC) and PFS.

  17. Cohorts 1 and 2: Exposure-efficacy relationships for zelenectide pevedotin maximum plasma concentration (Cmax)

    Timeframe: Until the end of treatment, up to approximately 4 years

    Quantitative modeling of the association between measured zelenectide pevedotin PK parameter (Cmax) and ORR.

  18. Cohorts 1 and 2: Exposure-efficacy relationships for zelenectide pevedotin Cmax

    Timeframe: Until the end of treatment, up to approximately 4 years

    Quantitative modeling of the association between measured zelenectide pevedotin PK parameter (Cmax) and PFS.

  19. Cohorts 1 and 2: Exposure-efficacy relationships for MMAE Cmax

    Timeframe: Until the end of treatment, up to approximately 4 years

    Quantitative modeling of the association between measured MMAE PK parameter (Cmax) and ORR.

  20. Cohorts 1 and 2: Exposure-efficacy relationships for MMAE Cmax

    Timeframe: Until the end of treatment, up to approximately 4 years

    Quantitative modeling of the association between measured MMAE PK parameter (Cmax) and PFS.

  21. Cohorts 1 and 2: Exposure-efficacy relationships for zelenectide pevedotin average plasma concentration (Cavg)

    Timeframe: Until the end of treatment, up to approximately 4 years

    Quantitative modeling of the association between measured zelenectide pevedotin PK parameter (Cavg) and ORR.

  22. Cohorts 1 and 2: Exposure-efficacy relationships for zelenectide pevedotin Cavg

    Timeframe: Until the end of treatment, up to approximately 4 years

    Quantitative modeling of the association between measured zelenectide pevedotin PK parameter (Cavg) and PFS.

  23. Cohorts 1 and 2: Exposure-efficacy relationships for MMAE Cavg

    Timeframe: Until the end of treatment, up to approximately 4 years

    Quantitative modeling of the association between measured MMAE PK parameter (Cavg) and ORR.

  24. Cohorts 1 and 2: Exposure-efficacy relationships for MMAE Cavg

    Timeframe: Until the end of treatment, up to approximately 4 years

    Quantitative modeling of the association between measured MMAE PK parameter (Cavg) and PFS.

  25. Cohorts 1 and 2: Exposure-safety relationships for zelenectide pevedotin AUC

    Timeframe: Until the end of treatment, up to approximately 4 years

    Quantitative modeling of the association between measured zelenectide pevedotin PK parameter (AUC) and clinical safety, measured by incidence of most frequent or relevant treatment emergent adverse events and treatment related adverse events

And 5 more, listed on the interactive page.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

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 primary 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 receiving study medications, 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
Sources for eligibility
clinicaltrials.gov

  • Rocky Mountain Cancer CenterDenver, United States
  • University of Miami - Sylvester Comprehensive Cancer CenterMiami, United States
  • Mount Sinai Medical Center of Florida, Inc.Miami Beach, United States
  • MoffittTampa, United States
  • University of Kansas Cancer CenterWestwood, United States
  • UofL Health Brown Cancer CenterLouisville, United States
  • Nebraska Cancer SpecialistsOmaha, United States
  • Montefiore Medical CenterThe Bronx, United States
  • Medical University of South Carolina (MUSC) - Hollings Cancer CenterCharleston, United States
  • Carolina Urologic Research CenterMyrtle Beach, United States
  • SCRI Oncology PartnersNashville, United States
  • MD Anderson Cancer CenterHouston, United States
  • University of Texas Health Science Center at San AntonioSan Antonio, United States
  • Centro de Diagnostico Urologico S.R.L.Buenos Aires, Argentina
  • Hospital Britanico de Buenos AiresBuenos Aires, Argentina
  • Hospital Sirio Libanes de Buenos AiresBuenos Aires, Argentina
  • Instituto Alexander FlemingBuenos Aires, Argentina
  • Fundacion Medica Rio Negro y NeuquenCipolletti, Argentina
  • Centro Medico Privado (CEMAIC)Córdoba, Argentina
  • Fundación CORI para la investigación y Prevención del CancerLa Rioja, Argentina
  • Centro De Investigacion Pergamino S.A.Pergamino, Argentina
  • Instituto de Oncologia de RosarioSanta Fe, Argentina
  • Clinica Viedma S.A.Viedma, Argentina
  • Cancer Research SAAdelaide, Australia
  • Mater Misericordiae Ltd, South BrisbaneBrisbane, Australia

And 77 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2023
  • U1111-1300-3791
  • 2023-504231-41
Sources for references
clinicaltrials.gov

Related records

Drugs (5)

Lead sponsors (1)

Conditions (2)

Targets (16)