Study BT8009-230 in Participants With Locally Advanced or Metastatic Urothelial Cancer (Duravelo-2)
- Conditions
- Metastatic Urothelial Cancer
- Interventions
- Registration Number
- NCT06225596
- Lead Sponsor
- BicycleTx Limited
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 956
-
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:
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1: BT8009 Arm 1 Pembrolizumab Participants will receive BT8009 and a standard dose of pembrolizumab. Cohort 1: BT8009 Arm 1 BT8009 Participants will receive BT8009 and a standard dose of pembrolizumab. Cohort 2: BT8009 Arm 1 BT8009 Participants will receive BT8009. Cohort 1: Arm 3 Gemcitabine + cisplatin Or carboplatin Participants will receive Platinum-based combination chemotherapy +/- avelumab maintenance Cohort 1: BT8009 Arm 2 BT8009 Participants will receive BT8009 and a standard dose of pembrolizumab. Cohort 2: BT8009 Arm 2 BT8009 Participants will receive BT8009. Cohort 2: Arm 3: BT8009 (Not Recruiting) BT8009 Participants will receive BT8009 and a standard dose of pembrolizumab. Cohort 1: BT8009 Arm 2 Pembrolizumab Participants will receive BT8009 and a standard dose of pembrolizumab. Cohort 2: Arm 3: BT8009 (Not Recruiting) Pembrolizumab Participants will receive BT8009 and a standard dose of pembrolizumab. Cohort 1: Arm 3 Avelumab Participants will receive Platinum-based combination chemotherapy +/- avelumab maintenance
- Primary Outcome Measures
Name Time Method 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) Up to approximately 6 years The time from randomization to date of first documentation of disease progression or death.
Cohort 2: Objective response rate (ORR) per RECIST 1.1 assessed by BICR Up to approximately 6 years The time from randomization to date of first documentation of disease progression or death.
- Secondary Outcome Measures
Name Time Method Cohort 2: PFS per RECIST v1.1 assessed by BICR Up to approximately 6 years The time from randomization to date of first documentation of disease progression or death.
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: DCR per RECIST 1.1 assessed by Investigator Up to approximately 6 years The time from Cycle 1 Day 1 to date of first documentation of disease progression or death
Cohorts 1 and 2: PFS per RECIST v1.1 assessed by Investigator Up to approximately 6 years The time from randomization to date of first documentation of disease progression or death.
Cohorts 1 and 2: ORR per RECIST 1.1 assessed by Investigator Up to approximately 6 years The time from randomization to date of first documentation of disease progression or death.
Cohorts 1 and 2: Overall survival (OS) rate Up to approximately 7 years The time from randomization to date of death from any cause.
Cohorts 1 and 2: Duration of response (DoR) per RECIST 1.1 assessed by BICR Up to approximately 6 years 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.
Cohorts 1 and 2: DoR per RECIST 1.1 assessed by Investigator Up to approximately 6 years 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.
Cohorts 1 and 2: Number of Participants with Clinically Significant Changes in vital signs Until the end of treatment, up to approximately 6 years Cohort 1: ORR per RECIST 1.1 assessed by BICR Up to approximately 6 years The time from randomization to date of first documentation of disease progression or death.
Cohorts 1 and 2: Disease control rate (DCR) per RECIST 1.1 assessed by BICR Up to approximately 6 years The time from randomization to date of first documentation of disease progression or death.
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: 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 Cohorts 1 and 2: Change from Baseline in Euroqol-5 Dimensions (EQ-5D) Questionnaire Until the end of treatment, up to approximately 6 years
Trial Locations
- Locations (169)
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Virginia K. Crosson Cancer Center at St. Jude Medical Center
🇺🇸Fullerton, California, United States
University of California - Irvine Medical Center
🇺🇸Orange, California, United States
Adventist Health St. Helena
🇺🇸Saint Helena, California, United States
University of California, San Francisco (UCSF)
🇺🇸San Francisco, California, United States
Rocky Mountain Cancer Center
🇺🇸Denver, Colorado, United States
Yale University School of Medicine - Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Medical Oncology Hematology Consultants
🇺🇸Newark, Delaware, United States
Cancer Specialists of North Florida
🇺🇸Jacksonville, Florida, United States
Mount Sinai Medical Center of Florida, Inc.
🇺🇸Miami Beach, Florida, United States
University of Miami - Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
AP Medical Research
🇺🇸Miami, Florida, United States
Moffitt
🇺🇸Tampa, Florida, United States
Southern Illinois University (SIU) - Simmons Cancer Institute
🇺🇸Springfield, Illinois, United States
Mission Cancer + Blood
🇺🇸Des Moines, Iowa, United States
University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
UofL Health Brown Cancer Center
🇺🇸Louisville, Kentucky, United States
Mary Bird Perkins Cancer Center
🇺🇸Baton Rouge, Louisiana, United States
Princess Margaret Hospital
🇨🇦Toronto, Canada
Nebraska Cancer Specialists
🇺🇸Omaha, Nebraska, United States
XCancer Omaha/Urology Cancer Center
🇺🇸Omaha, Nebraska, United States
Astera Cancer Care
🇺🇸East Brunswick, New Jersey, United States
Summit Health (New Jersey Urology)
🇺🇸Voorhees, New Jersey, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Columbia University Irving Medical Center
🇺🇸New York, New York, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Medical University of South Carolina (MUSC) - Hollings Cancer Center
🇺🇸Charleston, South Carolina, United States
Carolina Urologic Research Center
🇺🇸Myrtle Beach, South Carolina, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
The Center for Cancer and Blood Disorders
🇺🇸Fort Worth, Texas, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Centro de Diagnostico Urologico S.R.L.
🇦🇷Buenos Aires, Argentina
Hospital Britanico de Buenos Aires
🇦🇷Buenos Aires, Argentina
Hospital Sirio Libanes de Buenos Aires
🇦🇷Buenos Aires, Argentina
Instituto Alexander Fleming
🇦🇷Buenos Aires, Argentina
Fundacion Medica Rio Negro y Neuquen
🇦🇷Cipolletti, Argentina
Centro Medico Privado (CEMAIC)
🇦🇷Córdoba, Argentina
Fundación CORI para la investigación y Prevención del Cancer
🇦🇷La Rioja, Argentina
Centro De Investigacion Pergamino S.A.
🇦🇷Pergamino, Argentina
Instituto de Oncologia de Rosario
🇦🇷Santa Fe, Argentina
Clinica Viedma S.A.
🇦🇷Viedma, Argentina
Cancer Research SA
🇦🇺Adelaide, Australia
Mater Misericordiae Ltd, South Brisbane
🇦🇺Brisbane, Australia
Townsville Hospital and Health Service
🇦🇺Douglas, Australia
Barwon Health
🇦🇺Geelong, Australia
Calvary Mater Newcastle
🇦🇺Hunter, Australia
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Australia
Blacktown Hospital
🇦🇺New South Wales, Australia
Prince of Wales Hospital
🇦🇺Randwick, Australia
Icon Cancer Centre
🇦🇺South Brisbane, Australia
Gold Coast University Hospital
🇦🇺Southport, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Australia
Urologie und Andrologie Ordensklinikum Linz GmbH Elisabethinen
🇦🇹Linz, Austria
Krankenhaus der Barmherzigen Brüder Wien
🇦🇹Wien, Austria
Medizinische Universitaet Wien
🇦🇹Wien, Austria
ASBL Grand Hôpital de Charleroi (GHdC), Site Notre Dame
🇧🇪Charleroi, Belgium
General Hospital Maria Middelares
🇧🇪Gent, Belgium
University Hospital Gent
🇧🇪Gent, Belgium
Universitaire Ziekenhuizen Leuven
🇧🇪Leuven, Belgium
Fundacao PIO XII - Hospital de Amor
🇧🇷Barretos, Brazil
CEPEN - Centro de Pesquisa e Ensino em Oncologia de Santa Catarina
🇧🇷Florianópolis, Brazil
Oncosite - Centro de Pesquisa Clinica Em Oncologia
🇧🇷Ijuí, Brazil
Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa
🇧🇷Porto Alegre, Brazil
Hospital Sao Lucas - Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS)
🇧🇷Porto Alegre, Brazil
Hospital Alemao Oswaldo Cruz
🇧🇷São Paulo, Brazil
Hospital A.C. Camargo Cancer Center
🇧🇷São Paulo, Brazil
British Columbia Cancer Agency- Centre for the Southern Interior
🇨🇦Kelowna, Canada
McGill University Health Center
🇨🇦Québec, Canada
Cancer Care Manitoba
🇨🇦Winnipeg, Canada
Fundación Arturo López Pérez (FALP)
🇨🇱Santiago, Chile
Centro de Investigacion Clinica Bradford Hill
🇨🇱Santiago, Chile
Oncocentro APYS
🇨🇱Viña Del Mar, Chile
Aalborg University Hospital
🇩🇰Aalborg, Denmark
Service d'Oncologie Medicale - CHRU Besancon
🇫🇷Besançon, France
Institut Bergonie
🇫🇷Bordeaux Cedex, France
CHU Bordeaux - Hopital Saint-Andre
🇫🇷Bordeaux, France
Groupement de Cooperation Sanitaire (GCS) ELSAN - Clinique Victor Hugo
🇫🇷Le Mans, France
CHU de Limoges - Hopital Dupuytren 1
🇫🇷Limoges, France
Centre Leon Berard
🇫🇷Lyon, France
Institut Paoli-Calmettes
🇫🇷Marseille, France
ICM - Institut Regional du Cancer de Montpellier
🇫🇷Montpellier Cedex 5, France
Centre d'Oncologie de Gentilly
🇫🇷Nancy, France
Centre Antoine-Lacassagne
🇫🇷Nice, France
Institut Mutualiste Montsouris
🇫🇷Paris, France
AP-HP Hopital Europeen Georges Pompidou
🇫🇷Paris, France
HCL Centre Hospitalier Lyon Sud
🇫🇷Pierre-Benite Cedex, France
CHU Poitiers - Pole Regional de Cancerologie de Poitiers (PRC)
🇫🇷Poitiers, France
Institut Gustave Roussy
🇫🇷Villejuif, France
LTD High Technology Hospital Medcenter
🇬🇪Batumi, Georgia
The First University Clinic of Tbilisi State Medical University
🇬🇪Tbilisi, Georgia
New Vision University Hospital
🇬🇪Tbilisi, Georgia
Multiprofile Clinic Consilium Medulla LTD
🇬🇪Tbilisi, Georgia
Universitaetsklinikum Carl Gustav Carus Dresden
🇩🇪Dresden, Germany
Universitaetsklinikum Essen
🇩🇪Essen, Germany
Krankenhaus Nordwest GmbH
🇩🇪Frankfurt, Germany
Universitaetsklinikum Frankfurt - Klinikum der Johann Wolfgang Goethe Universitaet
🇩🇪Frankfurt, Germany
Universitaetsklinikum Freiburg
🇩🇪Freiburg, Germany
Georg-August-Universitaet Goettingen Stiftung oeffentlichen Rechts Universitaetsmedizin Goettingen
🇩🇪Göttingen, Germany
Marien Hospital Herne - Universitaetsklinikum der Ruhr-Universitaet Bochum
🇩🇪Herne, Germany
Universitaetsmedizin Mannheim
🇩🇪Mannheim, Germany
Universitaetsklinikum Muenster
🇩🇪Münster, Germany
Studienpraxis Urologie
🇩🇪Nürtingen, Germany
Universitaetsklinikum Tuebingen
🇩🇪Tübingen, Germany
Orszagos Onkologiai Intezet
🇭🇺Budapest, Hungary
Budapesti Uzsoki Utcai Korhaz
🇭🇺Budapest, Hungary
Somogy Varmegyei Kaposi Mor Oktato Korhaz
🇭🇺Kaposvár, Hungary
Bacs-Kiskun Varmegyei Oktatokorhaz
🇭🇺Kecskemét, Hungary
Shamir Medical Center
🇮🇱Be'er Ya'aqov, Israel
Rambam Health Care Campus
🇮🇱Haifa, Israel
Hadassah Hebrew University Medical Center
🇮🇱Jerusalem, Israel
Meir Medical Center
🇮🇱Kfar Saba, Israel
Rabin Medical Center - Beilinson Hospital
🇮🇱Petach Tikva, Israel
Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Centro Riferimento Oncologico - Aviano
🇮🇹Aviano, Italy
Ospedale Policlinico San Martino IRCCS
🇮🇹Genova, Italy
Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"
🇮🇹Napoli, Italy
Azienda Ospedaliera Santa Maria di Terni
🇮🇹Terni, Italy
Chungnam National University Hospital
🇰🇷Daejeon, Korea, Republic of
National Cancer Center
🇰🇷Goyang, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Gwangju, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Copernicus PL Sp. z o.o., Wojewodzkie Centrum Onkologii
🇵🇱Gdańsk, Poland
Spitale Pomorskie Sp.z.o.o ODDZIAL ONKOLOGII KLINICZNEJ
🇵🇱Gdynia, Poland
SCM Sp. z o.o.
🇵🇱Kraków, Poland
Mazowiecki Szpital Onkologiczny
🇵🇱Wieliszew, Poland
University Clinical Center of Serbia, Clinic of Urology
🇷🇸Belgrade, Serbia
National University Hospital
🇸🇬Singapore, Singapore
National Cancer Centre Singapore
🇸🇬Singapore, Singapore
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Clinic Barcelona
🇪🇸Barcelona, Spain
Institut Catala d'Oncologia - L'Hospitalet
🇪🇸Barcelona, Spain
Hospital Universitario Insular de Gran Canaria
🇪🇸Las Palmas De Gran Canaria, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Clinica Universidad de Navarra - Madrid
🇪🇸Madrid, Spain
Hospital Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Clinica Universidad de Navarra - Pamplona
🇪🇸Pamplona, Spain
Hospital Universitario Donostia
🇪🇸San Sebastián, Spain
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Spain
Hospital Clinico Universitario de Santiago
🇪🇸Santiago De Compostela, Spain
Instituto Valenciano de Oncologia
🇪🇸Valencia, Spain
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Chi Mei Medical Center
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Linkou Chang Gung Memorial Hospital (CGMHLK)
🇨🇳Taoyuan city, Taiwan
Liv Hospital Ankara
🇹🇷Ankara, Turkey
Trakya University Medical Faculty
🇹🇷Edirne, Turkey
Goztepe Prof. Dr. Suleyman Yalcin City Hospital
🇹🇷Istanbul, Turkey
Istinye Universitesi VM Medical Park Pendik Hastanesi
🇹🇷Istanbul, Turkey
Medical Point Izmir Hospital
🇹🇷İzmir, Turkey
Kocaeli University Faculty of Medicine
🇹🇷Kocaeli, Turkey
Bristol Haematology and Oncology Centre
🇬🇧Bristol, United Kingdom
Addenbrooke's Hospital
🇬🇧Cambridge, United Kingdom
St. Bartholomew's Hospital
🇬🇧London, United Kingdom
University College London Hospital
🇬🇧London, United Kingdom
Royal Free London NHS Foundation Trust
🇬🇧London, United Kingdom
Charing Cross Hospital
🇬🇧London, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Derriford Hospital
🇬🇧Plymouth, United Kingdom
The Royal Marsden Hospital
🇬🇧Sutton, United Kingdom