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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06225596




Registration number
NCT06225596
Ethics application status
Date submitted
12/01/2024
Date registered
26/01/2024
Date last updated
20/11/2024

Titles & IDs
Public title
Study BT8009-230 in Participants With Locally Advanced or Metastatic Urothelial Cancer (Duravelo-2)
Scientific 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)
Secondary ID [1] 0 0
2023-504231-41
Secondary ID [2] 0 0
BT8009-230
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Urothelial Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BT8009
Treatment: Drugs - BT8009
Treatment: Drugs - BT8009
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - Gemcitabine + cisplatin Or carboplatin
Treatment: Drugs - Avelumab

Experimental: Cohort 1: BT8009 Arm 1 - Participants will receive BT8009 and a standard dose of pembrolizumab.

Experimental: Cohort 1: BT8009 Arm 2 - Participants will receive BT8009 and a standard dose of pembrolizumab.

Active comparator: Cohort 1: Arm 3 - Participants will receive Platinum-based combination chemotherapy +/- avelumab maintenance

Experimental: Cohort 2: BT8009 Arm 1 - Participants will receive BT8009.

Experimental: Cohort 2: BT8009 Arm 2 - Participants will receive BT8009.

Experimental: Cohort 2: Arm 3: BT8009 (Not Recruiting) - Participants will receive BT8009 and a standard dose of pembrolizumab.


Treatment: Drugs: BT8009
Participants will receive BT8009 on Days 1, 8, and 15 of every 21-day cycle.

Treatment: Drugs: BT8009
Participants will receive BT8009 on Days 1 and 8 of every 21-day cycle.

Treatment: Drugs: BT8009
Participants will receive BT8009 on days 1, 8 +/- 15 schedule of every 21-day cycle.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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)
Timepoint [1] 0 0
Up to approximately 6 years
Primary outcome [2] 0 0
Cohort 2: Objective response rate (ORR) per RECIST 1.1 assessed by BICR
Timepoint [2] 0 0
Up to approximately 6 years
Secondary outcome [1] 0 0
Cohort 1: ORR per RECIST 1.1 assessed by BICR
Timepoint [1] 0 0
Up to approximately 6 years
Secondary outcome [2] 0 0
Cohorts 1 and 2: ORR per RECIST 1.1 assessed by Investigator
Timepoint [2] 0 0
Up to approximately 6 years
Secondary outcome [3] 0 0
Cohorts 1 and 2: Overall survival (OS) rate
Timepoint [3] 0 0
Up to approximately 7 years
Secondary outcome [4] 0 0
Cohorts 1 and 2: Duration of response (DoR) per RECIST 1.1 assessed by BICR
Timepoint [4] 0 0
Up to approximately 6 years
Secondary outcome [5] 0 0
Cohorts 1 and 2: DoR per RECIST 1.1 assessed by Investigator
Timepoint [5] 0 0
Up to approximately 6 years
Secondary outcome [6] 0 0
Cohorts 1 and 2: Disease control rate (DCR) per RECIST 1.1 assessed by BICR
Timepoint [6] 0 0
Up to approximately 6 years
Secondary outcome [7] 0 0
Cohorts 1 and 2: DCR per RECIST 1.1 assessed by Investigator
Timepoint [7] 0 0
Up to approximately 6 years
Secondary outcome [8] 0 0
Cohorts 1 and 2: PFS per RECIST v1.1 assessed by Investigator
Timepoint [8] 0 0
Up to approximately 6 years
Secondary outcome [9] 0 0
Cohort 2: PFS per RECIST v1.1 assessed by BICR
Timepoint [9] 0 0
Up to approximately 6 years
Secondary outcome [10] 0 0
Cohorts 1 and 2: Number of participants reporting adverse events (AEs) and Serious adverse events (SAEs)
Timepoint [10] 0 0
Until 30 days post last dose, up to approximately 6 years
Secondary outcome [11] 0 0
Cohorts 1 and 2: Number of Participants with Clinically Significant Changes in Laboratory Results
Timepoint [11] 0 0
Until the end of treatment, up to approximately 6 years
Secondary outcome [12] 0 0
Cohorts 1 and 2: Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG)
Timepoint [12] 0 0
Until the end of treatment, up to approximately 6 years
Secondary outcome [13] 0 0
Cohorts 1 and 2: Number of Participants with Clinically Significant Changes in vital signs
Timepoint [13] 0 0
Until the end of treatment, up to approximately 6 years
Secondary outcome [14] 0 0
Cohorts 1 and 2: Change from Baseline in Euroqol-5 Dimensions (EQ-5D) Questionnaire
Timepoint [14] 0 0
Until the end of treatment, up to approximately 6 years
Secondary outcome [15] 0 0
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)
Timepoint [15] 0 0
Until the end of treatment, up to approximately 6 years

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/01/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2030
Actual
Sample size
Target
956
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Cancer Research SA - Adelaide
Recruitment hospital [2] 0 0
Townsville Hospital and Health Service - Douglas
Recruitment hospital [3] 0 0
Barwon Health - Geelong
Recruitment hospital [4] 0 0
Calvary Mater Newcastle - Hunter
Recruitment hospital [5] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [6] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [7] 0 0
Icon Cancer Centre - South Brisbane
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
QLD 4814 - Douglas
Recruitment postcode(s) [3] 0 0
3220 - Geelong
Recruitment postcode(s) [4] 0 0
2310 - Hunter
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment postcode(s) [6] 0 0
2031 - Randwick
Recruitment postcode(s) [7] 0 0
4066 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
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United States of America
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California
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United States of America
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Florida
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United States of America
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Iowa
Country [5] 0 0
United States of America
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Kansas
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United States of America
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Kentucky
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United States of America
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Louisiana
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Michigan
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Nebraska
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New Jersey
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New York
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Ohio
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South Carolina
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Tennessee
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United States of America
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Texas
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Argentina
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Buenos Aires
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Argentina
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Córdoba
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Argentina
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La Rioja
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Argentina
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Santa Fe
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Argentina
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Viedma
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Belgium
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Gent
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Belgium
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Leuven
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Canada
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Kelowna
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Canada
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Québec
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Canada
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Toronto
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Chile
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Santiago
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Chile
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Viña Del Mar
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France
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Besançon
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France
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Bordeaux Cedex
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France
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Bordeaux
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France
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Le Mans
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France
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Limoges
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France
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Lyon
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France
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Montpellier Cedex 5
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France
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Nice
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France
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Paris
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France
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Pierre-Benite Cedex
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Georgia
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Batumi
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Georgia
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Tbilisi
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Germany
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Frankfurt
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Hungary
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Budapest
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Be'er Ya'aqov
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Haifa
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Israel
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Jerusalem
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Israel
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Kfar Saba
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Israel
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Petach Tikva
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Israel
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Tel Aviv
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Napoli
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Korea, Republic of
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Daejeon
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Goyang
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Gwangju
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Gdansk
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Barcelona
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Madrid
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Spain
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Pamplona
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Spain
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San Sebastián
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Spain
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Santander
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Spain
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Santiago De Compostela
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Spain
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Valencia
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Taiwan
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Kaohsiung
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Taiwan
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Taichung
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Taiwan
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Tainan
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Taiwan
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Taoyuan city
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Turkey
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Ankara
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Turkey
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Edirne
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Turkey
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Istanbul
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United Kingdom
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Bristol
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Cambridge
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London
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Manchester
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United Kingdom
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Plymouth
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United Kingdom
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Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
BicycleTx Limited
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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 (zelenectide pevedotin) 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.
Trial website
https://clinicaltrials.gov/study/NCT06225596
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
BicycleTx Limited
Address 0 0
Country 0 0
Phone 0 0
617-945-8155
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06225596