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NCT Number: NCT06225596

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

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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This study is active but is not currently recruiting participants.

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Key information

Conditions

Metastatic Urothelial Cancer Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Male Urogenital Diseases Neoplasms Neoplasms by Site Urinary Bladder Diseases Urinary Bladder Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Centro de Diagnostico Urologico S.R.L., Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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:
  • 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.
  • Prior neoadjuvant/adjuvant chemotherapy or monomethyl auristatin E (MMAE)-based therapy with recurrence >12 months from completion of therapy.
  • 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

Treatment and study plan

Zelenectide pevedotin

Drug

Participants will receive zelenectide pevedotin on Days 1, 8, and 15 of every 21-day cycle.

Other names: BT8009

Pembrolizumab

Drug

Participants will receive Pembrolizumab on Day 1 of every 21-day cycle. Pembrolizumab infusion will be started 30 minutes following the completion of the zelenectide pevedotin infusion.

Gemcitabine + cisplatin Or carboplatin

Drug

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

Drug

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.

Primary outcomes

  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

    Time frame: 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

    Time frame: 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

    Time frame: Up to approximately 4 years

Secondary outcomes

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

    Time frame: 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.

    Time frame: Up to approximately 4 years

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

    Time frame: Up to approximately 4 years

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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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)

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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)

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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)

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

  26. Cohorts 1 and 2: Exposure-safety relationships for MMAE AUC

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

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

  27. Cohorts 1 and 2: Exposure-safety relationships for zelenectide pevedotin Cmax

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

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

  28. Cohorts 1 and 2: Exposure-safety relationships for MMAE Cmax

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

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

  29. Cohorts 1 and 2: Exposure-safety relationships for zelenectide pevedotin Cavg

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

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

  30. Exposure-safety relationships for MMAE Cavg

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

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

Sponsors and collaborators

Lead sponsor

BicycleTx Limited

Industry

Registry information

Official study 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)

Important dates

Study start
2024
Primary completion
2028
Study completion
2028
First posted
Jan 26, 2024
Registry last updated
May 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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