Clinical trial NCT06225596: Study BT8009-230 in Participants With Locally Advanced or Metastatic Urothelial Cancer (Duravelo-2)
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Metastatic Urothelial Cancer
Keywords: Metastatic Urothelial Cancer
BT8009
Bladder cancer
Pembrolizumab
Chemotherapy
Avelumab
Zelenectide pevedotin
Lead sponsor: BicycleTx Limited
Sponsor class: INDUSTRY
First posted: 2024-01-26
Enrollment: 956
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 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 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

Primary outcomes:
measure: 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)
timeFrame: Up to approximately 6 years
measure: Cohort 2: Objective response rate (ORR) per RECIST 1.1 assessed by BICR
timeFrame: Up to approximately 6 years
Secondary outcomes:
measure: Cohort 1: ORR per RECIST 1.1 assessed by BICR
timeFrame: Up to approximately 6 years
measure: Cohorts 1 and 2: ORR per RECIST 1.1 assessed by Investigator
timeFrame: Up to approximately 6 years
measure: Cohorts 1 and 2: Overall survival (OS) rate
timeFrame: Up to approximately 7 years
measure: Cohorts 1 and 2: Duration of response (DoR) per RECIST 1.1 assessed by BICR
timeFrame: Up to approximately 6 years
measure: Cohorts 1 and 2: DoR per RECIST 1.1 assessed by Investigator
timeFrame: Up to approximately 6 years
measure: Cohorts 1 and 2: Disease control rate (DCR) per RECIST 1.1 assessed by BICR
timeFrame: Up to approximately 6 years
measure: Cohorts 1 and 2: DCR per RECIST 1.1 assessed by Investigator
timeFrame: Up to approximately 6 years
measure: Cohorts 1 and 2: PFS per RECIST v1.1 assessed by Investigator
timeFrame: Up to approximately 6 years
measure: Cohort 2: PFS per RECIST v1.1 assessed by BICR
timeFrame: Up to approximately 6 years
measure: Cohorts 1 and 2: Number of participants reporting adverse events (AEs) and Serious adverse events (SAEs)
timeFrame: Until 30 days post last dose, up to approximately 6 years
measure: Cohorts 1 and 2: Number of Participants with Clinically Significant Changes in Laboratory Results
timeFrame: Until the end of treatment, up to approximately 6 years
measure: Cohorts 1 and 2: Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG)
timeFrame: Until the end of treatment, up to approximately 6 years
measure: Cohorts 1 and 2: Number of Participants with Clinically Significant Changes in vital signs
timeFrame: Until the end of treatment, up to approximately 6 years
measure: Cohorts 1 and 2: Change from Baseline in Euroqol-5 Dimensions (EQ-5D) Questionnaire
timeFrame: Until the end of treatment, up to approximately 6 years
measure: 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)
timeFrame: Until the end of treatment, up to approximately 6 years
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Fullerton
country: United States
facility: Virginia K. Crosson Cancer Center at St. Jude Medical Center
state: California
city: Orange
country: United States
facility: University of California - Irvine Medical Center
state: California
city: Saint Helena
country: United States
facility: Adventist Health St. Helena
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco (UCSF)
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine - Yale Cancer Center
state: Connecticut
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants
state: Delaware
city: Jacksonville
country: United States
facility: Cancer Specialists of North Florida
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center of Florida, Inc.
state: Florida
city: Miami
country: United States
facility: University of Miami - Sylvester Comprehensive Cancer Center
state: Florida
city: Miami
country: United States
facility: AP Medical Research
state: Florida
city: Tampa
country: United States
facility: Moffitt
state: Florida
city: Springfield
country: United States
facility: Southern Illinois University (SIU) - Simmons Cancer Institute
state: Illinois
city: Des Moines
country: United States
facility: Mission Cancer + Blood
state: Iowa
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Louisville
country: United States
facility: UofL Health Brown Cancer Center
state: Kentucky
city: Baton Rouge
country: United States
facility: Mary Bird Perkins Cancer Center
state: Louisiana
city: Grand Rapids
country: United States
facility: Princess Margaret Hospital
state: Michigan
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Omaha
country: United States
facility: XCancer Omaha/Urology Cancer Center
state: Nebraska
city: East Brunswick
country: United States
facility: Astera Cancer Care
state: New Jersey
city: Voorhees
country: United States
facility: Summit Health (New Jersey Urology)
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC) - Hollings Cancer Center
state: South Carolina
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Fort Worth
country: United States
facility: The Center for Cancer and Blood Disorders
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Buenos Aires
country: Argentina
facility: Centro de Diagnostico Urologico S.R.L.
city: Buenos Aires
country: Argentina
facility: Hospital Britanico de Buenos Aires
city: Buenos Aires
country: Argentina
facility: Hospital Sirio Libanes de Buenos Aires
city: Buenos Aires
country: Argentina
facility: Instituto Alexander Fleming
city: Cipolletti
country: Argentina
facility: Fundacion Medica Rio Negro y Neuquen
city: Córdoba
country: Argentina
facility: Centro Medico Privado (CEMAIC)
city: La Rioja
country: Argentina
facility: Fundación CORI para la investigación y Prevención del Cancer
city: Pergamino
country: Argentina
facility: Centro De Investigacion Pergamino S.A.
city: Santa Fe
country: Argentina
facility: Instituto de Oncologia de Rosario
city: Viedma
country: Argentina
facility: Clinica Viedma S.A.
city: Adelaide
country: Australia
facility: Cancer Research SA
city: Brisbane
country: Australia
facility: Mater Misericordiae Ltd, South Brisbane
city: Douglas
country: Australia
facility: Townsville Hospital and Health Service
city: Geelong
country: Australia
facility: Barwon Health
city: Hunter
country: Australia
facility: Calvary Mater Newcastle
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
city: New South Wales
country: Australia
facility: Blacktown Hospital
city: Randwick
country: Australia
facility: Prince of Wales Hospital
city: South Brisbane
country: Australia
facility: Icon Cancer Centre
city: Southport
country: Australia
facility: Gold Coast University Hospital
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
city: Linz
country: Austria
facility: Urologie und Andrologie Ordensklinikum Linz GmbH Elisabethinen
city: Wien
country: Austria
facility: Krankenhaus der Barmherzigen Brüder Wien
city: Wien
country: Austria
facility: Medizinische Universitaet Wien
city: Charleroi
country: Belgium
facility: ASBL Grand Hôpital de Charleroi (GHdC), Site Notre Dame
city: Gent
country: Belgium
facility: General Hospital Maria Middelares
city: Gent
country: Belgium
facility: University Hospital Gent
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
city: Barretos
country: Brazil
facility: Fundacao PIO XII - Hospital de Amor
city: Florianópolis
country: Brazil
facility: CEPEN - Centro de Pesquisa e Ensino em Oncologia de Santa Catarina
city: Ijuí
country: Brazil
facility: Oncosite - Centro de Pesquisa Clinica Em Oncologia
city: Porto Alegre
country: Brazil
facility: Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas - Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS)
city: São Paulo
country: Brazil
facility: Hospital Alemao Oswaldo Cruz
city: São Paulo
country: Brazil
facility: Hospital A.C. Camargo Cancer Center
city: Kelowna
country: Canada
facility: British Columbia Cancer Agency- Centre for the Southern Interior
city: Québec
country: Canada
facility: McGill University Health Center
city: Toronto
country: Canada
facility: Princess Margaret Hospital
city: Winnipeg
country: Canada
facility: Cancer Care Manitoba
city: Santiago
country: Chile
facility: Fundación Arturo López Pérez (FALP)
city: Santiago
country: Chile
facility: Centro de Investigacion Clinica Bradford Hill
city: Viña Del Mar
country: Chile
facility: Oncocentro APYS
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Besançon
country: France
facility: Service d'Oncologie Medicale - CHRU Besancon
city: Bordeaux Cedex
country: France
facility: Institut Bergonie
city: Bordeaux
country: France
facility: CHU Bordeaux - Hopital Saint-Andre
city: Le Mans
country: France
facility: Groupement de Cooperation Sanitaire (GCS) ELSAN - Clinique Victor Hugo
city: Limoges
country: France
facility: CHU de Limoges - Hopital Dupuytren 1
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Montpellier Cedex 5
country: France
facility: ICM - Institut Regional du Cancer de Montpellier
city: Nancy
country: France
facility: Centre d'Oncologie de Gentilly
city: Nice
country: France
facility: Centre Antoine-Lacassagne
city: Paris
country: France
facility: Institut Mutualiste Montsouris
city: Paris
country: France
facility: AP-HP Hopital Europeen Georges Pompidou
city: Pierre-Benite Cedex
country: France
facility: HCL Centre Hospitalier Lyon Sud
city: Poitiers
country: France
facility: CHU Poitiers - Pole Regional de Cancerologie de Poitiers (PRC)
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Batumi
country: Georgia
facility: LTD High Technology Hospital Medcenter
city: Tbilisi
country: Georgia
facility: The First University Clinic of Tbilisi State Medical University
city: Tbilisi
country: Georgia
facility: New Vision University Hospital
city: Tbilisi
country: Georgia
facility: Multiprofile Clinic Consilium Medulla LTD
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus Dresden
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Frankfurt
country: Germany
facility: Krankenhaus Nordwest GmbH
city: Frankfurt
country: Germany
facility: Universitaetsklinikum Frankfurt - Klinikum der Johann Wolfgang Goethe Universitaet
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
city: Göttingen
country: Germany
facility: Georg-August-Universitaet Goettingen Stiftung oeffentlichen Rechts Universitaetsmedizin Goettingen
city: Herne
country: Germany
facility: Marien Hospital Herne - Universitaetsklinikum der Ruhr-Universitaet Bochum
city: Mannheim
country: Germany
facility: Universitaetsmedizin Mannheim
city: Münster
country: Germany
facility: Universitaetsklinikum Muenster
city: Nürtingen
country: Germany
facility: Studienpraxis Urologie
city: Tübingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet
city: Budapest
country: Hungary
facility: Budapesti Uzsoki Utcai Korhaz
city: Kaposvár
country: Hungary
facility: Somogy Varmegyei Kaposi Mor Oktato Korhaz
city: Kecskemét
country: Hungary
facility: Bacs-Kiskun Varmegyei Oktatokorhaz
city: Be'er Ya'aqov
country: Israel
facility: Shamir Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: Hadassah Hebrew University Medical Center
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center - Beilinson Hospital
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
city: Aviano
country: Italy
facility: Centro Riferimento Oncologico - Aviano
city: Genova
country: Italy
facility: Ospedale Policlinico San Martino IRCCS
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"
city: Terni
country: Italy
facility: Azienda Ospedaliera Santa Maria di Terni
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Goyang
country: Korea, Republic of
facility: National Cancer Center
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Gdańsk
country: Poland
facility: Copernicus PL Sp. z o.o., Wojewodzkie Centrum Onkologii
city: Gdynia
country: Poland
facility: Spitale Pomorskie Sp.z.o.o ODDZIAL ONKOLOGII KLINICZNEJ
city: Kraków
country: Poland
facility: SCM Sp. z o.o.
city: Wieliszew
country: Poland
facility: Mazowiecki Szpital Onkologiczny
city: Belgrade
country: Serbia
facility: University Clinical Center of Serbia, Clinic of Urology
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Barcelona
country: Spain
facility: Institut Catala d'Oncologia - L'Hospitalet
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Universitario Insular de Gran Canaria
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra - Madrid
city: Madrid
country: Spain
facility: Hospital Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra - Pamplona
city: San Sebastián
country: Spain
facility: Hospital Universitario Donostia
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Santiago De Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Tainan
country: Taiwan
facility: Chi Mei Medical Center
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan city
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital (CGMHLK)
city: Ankara
country: Turkey
facility: Liv Hospital Ankara
city: Edirne
country: Turkey
facility: Trakya University Medical Faculty
city: Istanbul
country: Turkey
facility: Goztepe Prof. Dr. Suleyman Yalcin City Hospital
city: Istanbul
country: Turkey
facility: Istinye Universitesi VM Medical Park Pendik Hastanesi
city: İzmir
country: Turkey
facility: Medical Point Izmir Hospital
city: Kocaeli
country: Turkey
facility: Kocaeli University Faculty of Medicine
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: London
country: United Kingdom
facility: St. Bartholomew's Hospital
city: London
country: United Kingdom
facility: University College London Hospital
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: London
country: United Kingdom
facility: Charing Cross Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital
Study officials:
References: