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

NCT06225596 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: BT8009-2302023-504231-41U1111-1300-3791
• Study Type: interventional
• Target: 956
• Locations: 21 countries
• Sites: 102

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.

Conditions

Metastatic Urothelial Cancer

Keywords

Metastatic Urothelial Cancer; BT8009; Bladder cancer; Pembrolizumab; Chemotherapy; Avelumab; Zelenectide pevedotin

Outcome Measures

Primary Outcomes (2)

• 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)

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

  Up to approximately 6 years

• Cohort 2: Objective response rate (ORR) per RECIST 1.1 assessed by BICR

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

  Up to approximately 6 years

Secondary Outcomes (15)

• Cohort 1: ORR per RECIST 1.1 assessed by BICR

  Up to approximately 6 years

• Cohorts 1 and 2: ORR per RECIST 1.1 assessed by Investigator

  Up to approximately 6 years

• Cohorts 1 and 2: Overall survival (OS) rate

  Up to approximately 7 years

• Cohorts 1 and 2: Duration of response (DoR) per RECIST 1.1 assessed by BICR

  Up to approximately 6 years

• Cohorts 1 and 2: DoR per RECIST 1.1 assessed by Investigator

  Up to approximately 6 years

Study Arms (6)

Cohort 1: BT8009 Arm 1

EXPERIMENTAL

Participants will receive BT8009 and a standard dose of pembrolizumab.

Drug: BT8009; Drug: Pembrolizumab

Cohort 1: BT8009 Arm 2

EXPERIMENTAL

Participants will receive BT8009 and a standard dose of pembrolizumab.

Drug: BT8009; Drug: Pembrolizumab

Cohort 1: Arm 3

ACTIVE COMPARATOR

Participants will receive Platinum-based combination chemotherapy +/- avelumab maintenance

Drug: Gemcitabine + cisplatin Or carboplatin; Drug: Avelumab

Cohort 2: BT8009 Arm 1

EXPERIMENTAL

Participants will receive BT8009.

Drug: BT8009

Cohort 2: BT8009 Arm 2

EXPERIMENTAL

Participants will receive BT8009.

Drug: BT8009

Cohort 2: Arm 3: BT8009 (Not Recruiting)

EXPERIMENTAL

Participants will receive BT8009 and a standard dose of pembrolizumab.

Drug: BT8009; Drug: Pembrolizumab

Interventions

BT8009 DRUG

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

Cohort 1: BT8009 Arm 1; Cohort 2: BT8009 Arm 1

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 BT8009 infusion.

Cohort 1: BT8009 Arm 1; Cohort 1: BT8009 Arm 2; Cohort 2: Arm 3: BT8009 (Not Recruiting)

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.

Cohort 1: Arm 3

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.

Cohort 1: Arm 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• BicycleTx Limited: lead

Study Sites (102)

Rocky Mountain Cancer Center

Denver, Colorado, 80218, United States

Location

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Mount Sinai Medical Center of Florida, Inc.

Miami Beach, Florida, 33140, United States

Location

Moffitt

Tampa, Florida, 33612, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

UofL Health Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Medical University of South Carolina (MUSC) - Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Centro de Diagnostico Urologico S.R.L.

Buenos Aires, C1120AAT, Argentina

Location

Hospital Britanico de Buenos Aires

Buenos Aires, C1280AEB, Argentina

Location

Hospital Sirio Libanes de Buenos Aires

Buenos Aires, C1419AHN, Argentina

Location

Instituto Alexander Fleming

Buenos Aires, C1426ANZ, Argentina

Location

Fundacion Medica Rio Negro y Neuquen

Cipolletti, R8324, Argentina

Location

Centro Medico Privado (CEMAIC)

Córdoba, X5008HHW, Argentina

Location

Fundación CORI para la investigación y Prevención del Cancer

La Rioja, 5300, Argentina

Location

Centro De Investigacion Pergamino S.A.

Pergamino, B2700CPM, Argentina

Location

Instituto de Oncologia de Rosario

Santa Fe, S2000KZE, Argentina

Location

Clinica Viedma S.A.

Viedma, 8500, Argentina

Location

Cancer Research SA

Adelaide, 5000, Australia

Location

Mater Misericordiae Ltd, South Brisbane

Brisbane, 4101, Australia

Location

Townsville Hospital and Health Service

Douglas, QLD 4814, Australia

Location

Barwon Health

Geelong, 3220, Australia

Location

Calvary Mater Newcastle

Hunter, 2310, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, 6009, Australia

Location

Blacktown Hospital

New South Wales, 2148, Australia

Location

Icon Cancer Centre

South Brisbane, 4066, Australia

Location

Gold Coast University Hospital

Southport, 4215, Australia

Location

General Hospital Maria Middelares

Ghent, 9000, Belgium

Location

University Hospital Gent

Ghent, 9000, Belgium

Location

Fundacao PIO XII - Hospital de Amor

Barretos, 14784-400, Brazil

Location

CEPEN - Centro de Pesquisa e Ensino em Oncologia de Santa Catarina

Florianópolis, 88020-210, Brazil

Location

Hospital Alemao Oswaldo Cruz

São Paulo, 01327-001, Brazil

Location

McGill University Health Center

Québec, H4A 3J1, Canada

Location

Princess Margaret Hospital

Toronto, M5G 2M9, Canada

Location

Fundación Arturo López Pérez (FALP)

Santiago, 7500921, Chile

Location

Centro de Investigacion Clinica Bradford Hill

Santiago, 8420000, Chile

Location

Oncocentro APYS

Viña del Mar, 2520598, Chile

Location

Service d'Oncologie Medicale - CHRU Besancon

Besançon, 25000, France

Location

CHU Bordeaux - Hopital Saint-Andre

Bordeaux, 33000, France

Location

Groupement de Cooperation Sanitaire (GCS) ELSAN - Clinique Victor Hugo

Le Mans, 72000, France

Location

HCL Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

LTD High Technology Hospital Medcenter

Batumi, 6000, Georgia

Location

The First University Clinic of Tbilisi State Medical University

Tbilisi, 0141, Georgia

Location

New Vision University Hospital

Tbilisi, 0159, Georgia

Location

Multiprofile Clinic Consilium Medulla LTD

Tbilisi, 0186, Georgia

Location

Universitaetsklinikum Essen

Essen, 45147, Germany

Location

Orszagos Onkologiai Intezet

Budapest, H-1122, Hungary

Location

Budapesti Uzsoki Utcai Korhaz

Budapest, H-1145, Hungary

Location

Rambam Health Care Campus

Haifa, 3109601, Israel

Location

Hadassah Hebrew University Medical Center

Jerusalem, 9112001, Israel

Location

Rabin Medical Center - Beilinson Hospital

Petah Tikva, 4941492, Israel

Location

Centro Riferimento Oncologico - Aviano

Aviano, 33081, Italy

Location

Ospedale Policlinico San Martino IRCCS

Genova, 16132, Italy

Location

Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"

Naples, 80131, Italy

Location

Copernicus PL Sp. z o.o., Wojewodzkie Centrum Onkologii

Gdansk, 80-210, Poland

Location

Mazowiecki Szpital Onkologiczny

Wieliszew, 05-135, Poland

Location

University Clinical Center of Serbia, Clinic of Urology

Belgrade, 11000, Serbia

Location

National University Hospital

Singapore, 119228, Singapore

Location

Chungnam National University Hospital

Daejeon, 35015, South Korea

Location

National Cancer Center

Goyang, 10408, South Korea

Location

Korea University Anam Hospital

Seoul, 02841, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 3722, South Korea

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08026, Spain

Location

Hospital Clinic Barcelona

Barcelona, 08036, Spain

Location

Institut Catala d'Oncologia - L'Hospitalet

Barcelona, 08908, Spain

Location

Hospital Universitario Insular de Gran Canaria

Las Palmas de Gran Canaria, 35016, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Clinica Universidad de Navarra - Madrid

Madrid, 28027, Spain

Location

Hospital Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Clinica Universidad de Navarra - Pamplona

Pamplona, 31008, Spain

Location

Hospital Universitario Donostia

San Sebastián, 20014, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, 39008, Spain

Location

Hospital Clinico Universitario de Santiago

Santiago de Compostela, 15706, Spain

Location

Instituto Valenciano de Oncologia

Valencia, 46009, Spain

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

Chi Mei Medical Center

Tainan, 710, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Linkou Chang Gung Memorial Hospital (CGMHLK)

Taoyuan, 333, Taiwan

Location

Trakya University Medical Faculty

Edirne, 22030, Turkey (Türkiye)

Location

Istinye Universitesi VM Medical Park Pendik Hastanesi

Istanbul, 34899, Turkey (Türkiye)

Location

Medical Point Izmir Hospital

Izmir, 35575, Turkey (Türkiye)

Location

Kocaeli University Faculty of Medicine

Kocaeli, 41380, Turkey (Türkiye)

Location

Bristol Haematology and Oncology Centre

Bristol, BS2 8ED, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

St. Bartholomew's Hospital

London, EC1A 7BE, United Kingdom

Location

University College London Hospital

London, NW1 2PG, United Kingdom

Location

Royal Free London NHS Foundation Trust

London, NW3 2QG, United Kingdom

Location

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

The Royal Marsden Hospital

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

pembrolizumab; Gemcitabine; Cisplatin; Carboplatin; avelumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2024
• First Posted: January 26, 2024
• Study Start: January 24, 2024
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

PL (2); TW (6); CA (2); GB (7); BR (3); SE (1); AU (9); HU (2); KR (7); TU (4); CL (3); FR (5); GE (4); DE (1); IT (3); ES (14); BE (2); IL (3); US (13); SG (1); AR (10)