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| ID | Type | Description | Link |
|---|---|---|---|
| 2023-504231-41 | EudraCT Number | ||
| U1111-1300-3791 | Other Identifier | UTN |
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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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: Zelenectide pevedotin Arm 1 | Experimental | Participants will receive zelenectide pevedotin and a standard dose of pembrolizumab. |
|
| Cohort 1: Zelenectide pevedotin Arm 2 | Experimental | Participants will receive zelenectide pevedotin and a standard dose of pembrolizumab. |
|
| Cohort 1: Arm 3 | Active Comparator | Participants will receive Platinum-based combination chemotherapy +/- avelumab maintenance |
|
| Cohort 2: Zelenectide pevedotin Arm 1 | Experimental | Participants will receive zelenectide pevedotin. |
|
| Cohort 2: Zelenectide pevedotin Arm 2 | Experimental | Participants will receive zelenectide pevedotin. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Zelenectide pevedotin | Drug | Participants will receive zelenectide pevedotin on Days 1, 8, and 15 of every 21-day cycle. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | The time from randomization to date of first documentation of disease progression or death. | Up to approximately 4 years |
| Cohort 2: PFS per RECIST v1.1 assessed by BICR of zelenectide pevedotin monotherapy in each treatment regimen | The time from randomization to date of first documentation of disease progression or death. | Up to approximately 4 years |
| Cohort 2: Objective response rate (ORR) per RECIST v1.1 assessed by BICR of zelenectide pevedotin monotherapy in each treatment regimen | Up to approximately 4 years |
| Measure | Description | Time Frame |
|---|---|---|
| Cohort 1: PFS per RECIST v1.1 assessed by BICR of zelenectide pevedotin combined treatment arms versus chemotherapy | The time from randomization to date of first documentation of disease progression or death. | Up to approximately 4 years |
| Cohort 1: ORR per RECIST v1.1 assessed by BICR of optimal dose zelenectide pevedotin in combination with pembrolizumab versus chemotherapy. |
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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:
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:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rocky Mountain Cancer Center | Denver | Colorado | 80218 | United States | ||
| University of Miami - Sylvester Comprehensive Cancer Center |
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|
| Zelenectide pevedotin | Drug | Participants will receive zelenectide pevedotin on Days 1 and 8 of every 21-day cycle. |
|
|
| 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. |
|
| Up to approximately 4 years |
| Cohort 1: ORR per RECIST v1.1 assessed by BICR of zelenectide pevedotin combined treatment arms versus chemotherapy | Up to approximately 4 years |
| Cohort 1: Overall survival (OS) rate of optimal dose zelenectide pevedotin in combination with pembrolizumab versus chemotherapy | The time from randomization to date of death from any cause. | Up to approximately 4 years |
| Cohort 1: Duration of response (DoR) per RECIST v1.1 assessed by BICR of optimal dose of zelenectide pevedotin in combination with pembrolizumab | The time from time of first documentation of objective response that is subsequently confirmed to date of first documentation of disease progression or death. | Up to approximately 4 years |
| Cohort 1: Disease control rate (DCR) per RECIST v1.1 assessed by BICR of optimal dose of zelenectide pevedotin in combination with pembrolizumab | The time from randomization to date of first documentation of disease progression or death. | Up to approximately 4 years |
| Cohort 1: PFS per RECIST v1.1 assessed by BICR of unselected zelenectide pevedotin dose in combination with pembrolizumab | The time from randomization to date of first documentation of disease progression or death. | Up to approximately 4 years |
| Cohort 1: OS rate of zelenectide pevedotin combined treatment arms in combination with pembrolizumab versus chemotherapy | The time from randomization to date of death from any cause | Up to approximately 4 years |
| Cohort 2: DoR per RECIST v1.1 assessed by BICR in each treatment regimen | The time from time of first documentation of objective response that is subsequently confirmed to date of first documentation of disease progression or death. | Up to approximately 4 years |
| Cohort 2: DCR per RECIST v1.1 assessed by BICR in each treatment regimen | The time from cycle 1 Day 1 to date of first documentation of disease progression or death | Up to approximately 4 years |
| Cohort 2: OS rate in each treatment regimen | The time from randomization to date of death from any cause | Up to approximately 4 years |
| Cohorts 1 and 2: Safety and tolerability of each treatment regimen | Safety will be reported as incidence, severity, seriousness, relationship to study and types of adverse events | Until 30 days post last dose, up to approximately 4 years |
| Cohorts 1 and 2: Exposure-efficacy relationships for zelenectide pevedotin area under the plasma concentration-time curve (AUC) | Quantitative modeling of the association between measured zelenectide pevedotin pharmacokinetic (PK) parameter (AUC) and ORR. | Until the end of treatment, up to approximately 4 years |
| Cohorts 1 and 2: Exposure-efficacy relationships for zelenectide pevedotin AUC | Quantitative modeling of the association between measured zelenectide pevedotin PK parameter (AUC) and PFS. | Until the end of treatment, up to approximately 4 years |
| Cohorts 1 and 2: Exposure-efficacy relationships for monomethyl auristatin (MMAE) AUC | Quantitative modeling of the association between measured MMAE PK parameter (AUC) and ORR. | Until the end of treatment, up to approximately 4 years |
| Cohorts 1 and 2: Exposure-efficacy relationships for MMAE AUC | Quantitative modeling of the association between measured MMAE PK parameter (AUC) and PFS. | Until the end of treatment, up to approximately 4 years |
| Cohorts 1 and 2: Exposure-efficacy relationships for zelenectide pevedotin maximum plasma concentration (Cmax) | Quantitative modeling of the association between measured zelenectide pevedotin PK parameter (Cmax) and ORR. | Until the end of treatment, up to approximately 4 years |
| Cohorts 1 and 2: Exposure-efficacy relationships for zelenectide pevedotin Cmax | Quantitative modeling of the association between measured zelenectide pevedotin PK parameter (Cmax) and PFS. | Until the end of treatment, up to approximately 4 years |
| Cohorts 1 and 2: Exposure-efficacy relationships for MMAE Cmax | Quantitative modeling of the association between measured MMAE PK parameter (Cmax) and ORR. | Until the end of treatment, up to approximately 4 years |
| Cohorts 1 and 2: Exposure-efficacy relationships for MMAE Cmax | Quantitative modeling of the association between measured MMAE PK parameter (Cmax) and PFS. | Until the end of treatment, up to approximately 4 years |
| Cohorts 1 and 2: Exposure-efficacy relationships for zelenectide pevedotin average plasma concentration (Cavg) | Quantitative modeling of the association between measured zelenectide pevedotin PK parameter (Cavg) and ORR. | Until the end of treatment, up to approximately 4 years |
| Cohorts 1 and 2: Exposure-efficacy relationships for zelenectide pevedotin Cavg | Quantitative modeling of the association between measured zelenectide pevedotin PK parameter (Cavg) and PFS. | Until the end of treatment, up to approximately 4 years |
| Cohorts 1 and 2: Exposure-efficacy relationships for MMAE Cavg | Quantitative modeling of the association between measured MMAE PK parameter (Cavg) and ORR. | Until the end of treatment, up to approximately 4 years |
| Cohorts 1 and 2: Exposure-efficacy relationships for MMAE Cavg | Quantitative modeling of the association between measured MMAE PK parameter (Cavg) and PFS. | Until the end of treatment, up to approximately 4 years |
| Cohorts 1 and 2: Exposure-safety relationships for zelenectide pevedotin AUC | 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 | Until the end of treatment, up to approximately 4 years |
| Cohorts 1 and 2: Exposure-safety relationships for MMAE AUC | 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. | Until the end of treatment, up to approximately 4 years |
| Cohorts 1 and 2: Exposure-safety relationships for zelenectide pevedotin Cmax | 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. | Until the end of treatment, up to approximately 4 years |
| Cohorts 1 and 2: Exposure-safety relationships for MMAE Cmax | 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. | Until the end of treatment, up to approximately 4 years |
| Cohorts 1 and 2: Exposure-safety relationships for zelenectide pevedotin Cavg | 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. | Until the end of treatment, up to approximately 4 years |
| Exposure-safety relationships for MMAE Cavg | 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. | Until the end of treatment, up to approximately 4 years |
| Miami |
| Florida |
| 33136 |
| United States |
| Mount Sinai Medical Center of Florida, Inc. | Miami Beach | Florida | 33140 | United States |
| Moffitt | Tampa | Florida | 33612 | United States |
| University of Kansas Cancer Center | Westwood | Kansas | 66205 | United States |
| UofL Health Brown Cancer Center | Louisville | Kentucky | 40202 | United States |
| Nebraska Cancer Specialists | Omaha | Nebraska | 68130 | United States |
| Montefiore Medical Center | The Bronx | New York | 10461 | United States |
| Medical University of South Carolina (MUSC) - Hollings Cancer Center | Charleston | South Carolina | 29425 | United States |
| Carolina Urologic Research Center | Myrtle Beach | South Carolina | 29572 | United States |
| SCRI Oncology Partners | Nashville | Tennessee | 37203 | United States |
| MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| University of Texas Health Science Center at San Antonio | San Antonio | Texas | 78229 | United States |
| Centro de Diagnostico Urologico S.R.L. | Buenos Aires | C1120AAT | Argentina |
| Hospital Britanico de Buenos Aires | Buenos Aires | C1280AEB | Argentina |
| Hospital Sirio Libanes de Buenos Aires | Buenos Aires | C1419AHN | Argentina |
| Instituto Alexander Fleming | Buenos Aires | C1426ANZ | Argentina |
| Fundacion Medica Rio Negro y Neuquen | Cipolletti | R8324 | Argentina |
| Centro Medico Privado (CEMAIC) | Córdoba | X5008HHW | Argentina |
| Fundación CORI para la investigación y Prevención del Cancer | La Rioja | 5300 | Argentina |
| Centro De Investigacion Pergamino S.A. | Pergamino | B2700CPM | Argentina |
| Instituto de Oncologia de Rosario | Santa Fe | S2000KZE | Argentina |
| Clinica Viedma S.A. | Viedma | 8500 | Argentina |
| Cancer Research SA | Adelaide | 5000 | Australia |
| Mater Misericordiae Ltd, South Brisbane | Brisbane | 4101 | Australia |
| Townsville Hospital and Health Service | Douglas | QLD 4814 | Australia |
| Barwon Health | Geelong | 3220 | Australia |
| Calvary Mater Newcastle | Hunter | 2310 | Australia |
| Sir Charles Gairdner Hospital | Nedlands | 6009 | Australia |
| Blacktown Hospital | New South Wales | 2148 | Australia |
| Icon Cancer Centre | South Brisbane | 4066 | Australia |
| Gold Coast University Hospital | Southport | 4215 | Australia |
| General Hospital Maria Middelares | Ghent | 9000 | Belgium |
| University Hospital Gent | Ghent | 9000 | Belgium |
| Fundacao PIO XII - Hospital de Amor | Barretos | 14784-400 | Brazil |
| CEPEN - Centro de Pesquisa e Ensino em Oncologia de Santa Catarina | Florianópolis | 88020-210 | Brazil |
| Hospital Alemao Oswaldo Cruz | São Paulo | 01327-001 | Brazil |
| McGill University Health Center | Québec | H4A 3J1 | Canada |
| Princess Margaret Hospital | Toronto | M5G 2M9 | Canada |
| Fundación Arturo López Pérez (FALP) | Santiago | 7500921 | Chile |
| Centro de Investigacion Clinica Bradford Hill | Santiago | 8420000 | Chile |
| Oncocentro APYS | Viña del Mar | 2520598 | Chile |
| Service d'Oncologie Medicale - CHRU Besancon | Besançon | 25000 | France |
| CHU Bordeaux - Hopital Saint-Andre | Bordeaux | 33000 | France |
| Groupement de Cooperation Sanitaire (GCS) ELSAN - Clinique Victor Hugo | Le Mans | 72000 | France |
| HCL Centre Hospitalier Lyon Sud | Pierre-Bénite | 69495 | France |
| Institut Gustave Roussy | Villejuif | 94805 | France |
| LTD High Technology Hospital Medcenter | Batumi | 6000 | Georgia |
| The First University Clinic of Tbilisi State Medical University | Tbilisi | 0141 | Georgia |
| New Vision University Hospital | Tbilisi | 0159 | Georgia |
| Multiprofile Clinic Consilium Medulla LTD | Tbilisi | 0186 | Georgia |
| Universitaetsklinikum Essen | Essen | 45147 | Germany |
| Orszagos Onkologiai Intezet | Budapest | H-1122 | Hungary |
| Budapesti Uzsoki Utcai Korhaz | Budapest | H-1145 | Hungary |
| Rambam Health Care Campus | Haifa | 3109601 | Israel |
| Hadassah Hebrew University Medical Center | Jerusalem | 9112001 | Israel |
| Rabin Medical Center - Beilinson Hospital | Petah Tikva | 4941492 | Israel |
| Centro Riferimento Oncologico - Aviano | Aviano | 33081 | Italy |
| Ospedale Policlinico San Martino IRCCS | Genova | 16132 | Italy |
| Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" | Naples | 80131 | Italy |
| Copernicus PL Sp. z o.o., Wojewodzkie Centrum Onkologii | Gdansk | 80-210 | Poland |
| Mazowiecki Szpital Onkologiczny | Wieliszew | 05-135 | Poland |
| University Clinical Center of Serbia, Clinic of Urology | Belgrade | 11000 | Serbia |
| National University Hospital | Singapore | 119228 | Singapore |
| Chungnam National University Hospital | Daejeon | 35015 | South Korea |
| National Cancer Center | Goyang | 10408 | South Korea |
| Korea University Anam Hospital | Seoul | 02841 | South Korea |
| Seoul National University Hospital | Seoul | 03080 | South Korea |
| Asan Medical Center | Seoul | 05505 | South Korea |
| Samsung Medical Center | Seoul | 06351 | South Korea |
| Severance Hospital, Yonsei University Health System | Seoul | 3722 | South Korea |
| Hospital de la Santa Creu i Sant Pau | Barcelona | 08026 | Spain |
| Hospital Clinic Barcelona | Barcelona | 08036 | Spain |
| Institut Catala d'Oncologia - L'Hospitalet | Barcelona | 08908 | Spain |
| Hospital Universitario Insular de Gran Canaria | Las Palmas de Gran Canaria | 35016 | Spain |
| Hospital General Universitario Gregorio Maranon | Madrid | 28007 | Spain |
| Clinica Universidad de Navarra - Madrid | Madrid | 28027 | Spain |
| Hospital Fundacion Jimenez Diaz | Madrid | 28040 | Spain |
| Hospital Universitario 12 de Octubre | Madrid | 28041 | Spain |
| Hospital Universitario La Paz | Madrid | 28046 | Spain |
| Clinica Universidad de Navarra - Pamplona | Pamplona | 31008 | Spain |
| Hospital Universitario Donostia | San Sebastián | 20014 | Spain |
| Hospital Universitario Marques de Valdecilla | Santander | 39008 | Spain |
| Hospital Clinico Universitario de Santiago | Santiago de Compostela | 15706 | Spain |
| Instituto Valenciano de Oncologia | Valencia | 46009 | Spain |
| Kaohsiung Medical University Chung-Ho Memorial Hospital | Kaohsiung City | 807 | Taiwan |
| China Medical University Hospital | Taichung | 40447 | Taiwan |
| National Cheng Kung University Hospital | Tainan | 704 | Taiwan |
| Chi Mei Medical Center | Tainan | 710 | Taiwan |
| National Taiwan University Hospital | Taipei | 10002 | Taiwan |
| Linkou Chang Gung Memorial Hospital (CGMHLK) | Taoyuan City | 333 | Taiwan |
| Trakya University Medical Faculty | Edirne | 22030 | Turkey (Türkiye) |
| Istinye Universitesi VM Medical Park Pendik Hastanesi | Istanbul | 34899 | Turkey (Türkiye) |
| Medical Point Izmir Hospital | Izmir | 35575 | Turkey (Türkiye) |
| Kocaeli University Faculty of Medicine | Kocaeli | 41380 | Turkey (Türkiye) |
| Bristol Haematology and Oncology Centre | Bristol | BS2 8ED | United Kingdom |
| Addenbrooke's Hospital | Cambridge | CB2 0QQ | United Kingdom |
| St. Bartholomew's Hospital | London | EC1A 7BE | United Kingdom |
| University College London Hospital | London | NW1 2PG | United Kingdom |
| Royal Free London NHS Foundation Trust | London | NW3 2QG | United Kingdom |
| Derriford Hospital | Plymouth | PL6 8DH | United Kingdom |
| The Royal Marsden Hospital | Sutton | SM2 5PT | United Kingdom |
| ID | Term |
|---|---|
| D001749 | Urinary Bladder Neoplasms |
| ID | Term |
|---|---|
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D001745 | Urinary Bladder Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| C582435 | pembrolizumab |
| D000093542 | Gemcitabine |
| D002945 | Cisplatin |
| D016190 | Carboplatin |
| C000609138 | avelumab |
| ID | Term |
|---|---|
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
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