A Study of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib, Versus Pembrolizumab and Lenvatinib, for Treatment of Advanced Clear Cell Renal Cell Carcinoma (MK-6482-012)

Phase 3

Active, not recruiting

• Conditions: Carcinoma, Renal Cell
• Interventions: Biological: Pembrolizumab; Biological: Pembrolizumab/Quavonlimab; Drug: Belzutifan; Drug: Lenvatinib

• Registration Number: NCT04736706
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

The goal of this study is to evaluate the efficacy and safety of pembrolizumab plus belzutifan plus lenvatinib or pembrolizumab/quavonlimab plus lenvatinib versus pembrolizumab plus lenvatinib as first-line treatment in participants with advanced clear cell renal cell carcinoma (ccRCC).

The primary hypotheses are (1) pembrolizumab plus belzutifan plus lenvatinib is superior to pembrolizumab plus lenvatinib with respect to progression-free survival (PFS) and overall survival (OS), in advanced ccRCC participants; and (2) pembrolizumab/quavonlimab plus lenvatinib is superior to pembrolizumab plus lenvatinib with respect to PFS and OS, in advanced ccRCC participants.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-01-29
• Study First Submitted QC: 2021-01-29
• Study First Posted: 2021-02-03
• Study Start: 2021-04-14
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-14
• Last Update Posted: 2024-11-18
• Primary Completion: 2026-10-29
• Study Completion: 2026-10-29

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 1653

Inclusion Criteria

• Has histologically confirmed diagnosis of RCC with clear cell component.
• Has received no prior systemic therapy for advanced ccRCC
• Male participants are abstinent from heterosexual intercourse or agree to use contraception during and for at least 7 days after last dose of study intervention with belzutifan and lenvatinib.
• Female participants are not pregnant or breastfeeding and are either not a woman of child-bearing potential (WOCBP) or use a contraceptive method that is highly effective or are abstinent from heterosexual intercourse during the intervention period and for at least 120 days after pembrolizumab or pembrolizumab/quavonlimab or for at least 30 days after last dose of lenvatinib or belzutifan, whichever occurs last
• Has adequately controlled blood pressure with or without antihypertensive medications
• Has adequate organ function.
• Participants receiving bone resorptive therapy must have therapy initiated at least 2 weeks prior to randomization/allocation

Exclusion Criteria

• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has had major surgery, other than nephrectomy within 4 weeks prior to randomization
• Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has received prior radiotherapy within 2 weeks prior to first dose of study intervention
• Has hypoxia or requires intermittent supplemental oxygen or requires chronic supplemental oxygen
• Has clinically significant cardiac disease within 12 months from first dose of study intervention
• Has a history of interstitial lung disease
• Has symptomatic pleural effusion; a participant who is clinically stable following treatment of this condition is eligible
• Has preexisting gastrointestinal or non-gastrointestinal fistula
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
• Has a known psychiatric or substance abuse disorder that would interfere with requirements of the study
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study drug; killed vaccines are allowed
• Has an active autoimmune disease that has required systemic treatment in the past 2 years
• Has a history of noninfectious pneumonitis that required steroids or has current pneumonitis
• Has an active infection requiring systemic therapy
• Has a known history of human immunodeficiency virus (HIV) infection
• Has a known history of Hepatitis B
• Has radiographic evidence of intratumoral cavitation, encasement or invasion of a major blood vessel
• Has clinically significant history of bleeding within 3 months prior to randomization
• Has had an allogenic tissue/solid organ transplant

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pembrolizumab + Belzutifan + Lenvatinib	Pembrolizumab	Participants will receive pembrolizumab 400 mg PLUS belzutifan 120 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered intravenously (IV) once every 6 weeks (Q6W) for up to 18 administrations (up to \~2 years). Belzutifan and lenvatinib will be administered orally once daily (QD) until progressive disease or discontinuation.
Pembrolizumab/Quavonlimab + Lenvatinib	Pembrolizumab/Quavonlimab	Participants will receive pembrolizumab/quavonlimab (co-formulation of pembrolizumab 400 mg and quavonlimab 25 mg) PLUS lenvatinib 20 mg. Pembrolizumab/quavonlimab will be administered IV Q6W for up to 18 administrations (up to \~2 years). Lenvatinib will be administered orally QD until progressive disease or discontinuation.
Pembrolizumab + Lenvatinib	Pembrolizumab	Participants will receive pembrolizumab 400 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered IV Q6W for up to 18 administrations (up to \~2 years). Lenvatinib will be administered orally QD until progressive disease or discontinuation.
Pembrolizumab + Belzutifan + Lenvatinib	Lenvatinib	Participants will receive pembrolizumab 400 mg PLUS belzutifan 120 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered intravenously (IV) once every 6 weeks (Q6W) for up to 18 administrations (up to \~2 years). Belzutifan and lenvatinib will be administered orally once daily (QD) until progressive disease or discontinuation.
Pembrolizumab/Quavonlimab + Lenvatinib	Lenvatinib	Participants will receive pembrolizumab/quavonlimab (co-formulation of pembrolizumab 400 mg and quavonlimab 25 mg) PLUS lenvatinib 20 mg. Pembrolizumab/quavonlimab will be administered IV Q6W for up to 18 administrations (up to \~2 years). Lenvatinib will be administered orally QD until progressive disease or discontinuation.
Pembrolizumab + Lenvatinib	Lenvatinib	Participants will receive pembrolizumab 400 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered IV Q6W for up to 18 administrations (up to \~2 years). Lenvatinib will be administered orally QD until progressive disease or discontinuation.
Pembrolizumab + Belzutifan + Lenvatinib	Belzutifan	Participants will receive pembrolizumab 400 mg PLUS belzutifan 120 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered intravenously (IV) once every 6 weeks (Q6W) for up to 18 administrations (up to \~2 years). Belzutifan and lenvatinib will be administered orally once daily (QD) until progressive disease or discontinuation.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)	Up to approximately 46 months	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR based on RECIST 1.1 will be presented.
Overall Survival (OS)	Up to approximately 66 months	OS is defined as the time from randomization to death due to any cause.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR	Up to approximately 46 months	ORR is defined as the percentage of participants who have a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience a CR or PR as assessed by BICR based on RECIST 1.1 will be presented.
Number of Participants Who Experienced At least One Adverse Event (AE)	Up to approximately 66 months	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience at least one AE will be presented.
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR	Up to approximately 66 months	For participants who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until PD or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. The DOR as assessed by BICR based on RECIST 1.1 will be presented.
Number of Participants Who Discontinue Study Treatment Due to an AE	Up to approximately 66 months	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE will be presented.

Trial Locations

Locations (262)

Hartford Hospital ( Site 0024); 🇺🇸 Hartford, Connecticut, United States

Cedars Sinai Medical Center ( Site 0027); 🇺🇸 Los Angeles, California, United States

New England Cancer Specialists ( Site 0082); 🇺🇸 Scarborough, Maine, United States

HealthPartners Cancer Research Center-HealthPartners Frauenshuh Cancer Center ( Site 0005); 🇺🇸 Saint Louis Park, Minnesota, United States

Sunnybrook Research Institute ( Site 0116); 🇨🇦 Toronto, Ontario, Canada

Parkview Cancer Institute ( Site 0088); 🇺🇸 Fort Wayne, Indiana, United States

Emory University Winship Cancer Institute ( Site 0012); 🇺🇸 Atlanta, Georgia, United States

Wits Clinical Research ( Site 3012); 🇿🇦 Johannesburg, Gauteng, South Africa

Barts Health NHS Trust - St Bartholomew s Hospital ( Site 3116); 🇬🇧 London, England, United Kingdom

Rush University Medical Center ( Site 0040); 🇺🇸 Chicago, Illinois, United States

Massachusetts General Hospital ( Site 0094); 🇺🇸 Boston, Massachusetts, United States

Dana Farber Cancer Institute ( Site 0093); 🇺🇸 Boston, Massachusetts, United States

UTSW Medical Center ( Site 0015); 🇺🇸 Dallas, Texas, United States

Nippon Medical School Hospital ( Site 5006); 🇯🇵 Tokyo, Japan

Hospital Universitario 12 de Octubre ( Site 1505); 🇪🇸 Madrid, Spain

Hospital Clinico San Carlos ( Site 1503); 🇪🇸 Madrid, Spain

Hospital Universitario Virgen de la Victoria ( Site 1504); 🇪🇸 Malaga, Spain

Beth Israel Deaconess Medical Center ( Site 0089); 🇺🇸 Boston, Massachusetts, United States

Lahey Hospital & Medical Center ( Site 0090); 🇺🇸 Burlington, Massachusetts, United States

Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0302); 🇧🇷 Sao Paulo, Brazil

Tom Baker Cancer Centre ( Site 0119); 🇨🇦 Calgary, Alberta, Canada

Instituto de Cancerología S.A Clínica de las Americas (ICCLA) ( Site 0500); 🇨🇴 Medellin, Antioquia, Colombia

Hospital H+ Queretaro-Cuidados Oncológicos ( Site 0608); 🇲🇽 Santiago de Queretaro, Queretaro, Mexico

Centro de Investigacion Clinica de Oaxaca ( Site 0605); 🇲🇽 Oaxaca, Mexico

Severance Hospital Yonsei University Health System ( Site 4204); 🇰🇷 Seoul, Korea, Republic of

Uniwersytecki Szpital Kliniczny w Poznaniu ( Site 2406); 🇵🇱 Poznan, Wielkopolskie, Poland

Cancercare Rondebosch Oncology ( Site 3005); 🇿🇦 Rondebosch, Western Cape, South Africa

National Cheng Kung University Hospital ( Site 4404); 🇨🇳 Tainan, Taiwan

Ankara Universitesi Tip Fakultesi ( Site 2902); 🇹🇷 Ankara, Turkey

Dokuz Eylul Universitesi Tip Fakultesi Hastanesi ( Site 2905); 🇹🇷 Izmir, Turkey

Siriraj Hospital ( Site 4501); 🇹🇭 Bangkok, Krung Thep Maha Nakhon, Thailand

ME І.І. Mechnykov Dnipro Regional Clinical Hospital ( Site 2710); 🇺🇦 Dnipropetrovsk, Dnipropetrovska Oblast, Ukraine

Lviv State Regional Oncological Center ( Site 2712); 🇺🇦 Lviv, Lvivska Oblast, Ukraine

S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 2501); 🇷🇴 Craiova, Dolj, Romania

Vanderbilt University Medical Center ( Site 0069); 🇺🇸 Nashville, Tennessee, United States

Liga Norte Riograndense Contra o Cancer ( Site 0308); 🇧🇷 Natal, Rio Grande Do Norte, Brazil

Fiona Stanley Hospital ( Site 4009); 🇦🇺 Murdock, Western Australia, Australia

Regions Hospital ( Site 0095); 🇺🇸 Saint Paul, Minnesota, United States

Hospital Sultan Ismail ( Site 4303); 🇲🇾 Johor Bahru, Johor, Malaysia

Centro Avançado de Tratamento Oncológico- CENATRON-Clinical Research ( Site 0303); 🇧🇷 Belo Horizonte, Minas Gerais, Brazil

Clinique Francois Chenieux ( Site 1209); 🇫🇷 Limoges, Haute-Vienne, France

Hospital de Clinicas de Porto Alegre ( Site 0310); 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

Chernihiv Medical Center of Modern Oncology ( Site 2709); 🇺🇦 Chernihiv, Chernihivska Oblast, Ukraine

Henry Ford Hospital ( Site 0038); 🇺🇸 Detroit, Michigan, United States

Oregon Health & Science University ( Site 0071); 🇺🇸 Portland, Oregon, United States

The University of Alabama at Birmingham ( Site 0010); 🇺🇸 Birmingham, Alabama, United States

UC San Diego ( Site 0050); 🇺🇸 La Jolla, California, United States

University of California Irvine ( Site 0029); 🇺🇸 Orange, California, United States

UCLA Hematology Oncology Santa Monica ( Site 0048); 🇺🇸 Santa Monica, California, United States

University Cancer & Blood Center, LLC ( Site 0057); 🇺🇸 Athens, Georgia, United States

Cancer & Hematology Centers of Western Michigan ( Site 0018); 🇺🇸 Grand Rapids, Michigan, United States

University of Mississippi Medical Center ( Site 0037); 🇺🇸 Jackson, Mississippi, United States

Roswell Park Cancer Institute ( Site 0032); 🇺🇸 Buffalo, New York, United States

R.J. Zuckerberg Cancer Center-Medical Oncology ( Site 0013); 🇺🇸 Lake Success, New York, United States

Sidney Kimmel Center for Prostate and Urologic Cancers ( Site 0055); 🇺🇸 New York, New York, United States

Lyell McEwin Hospital ( Site 4004); 🇦🇺 Elizabeth Vale, South Australia, Australia

Central Washington Health Services Association d/b/a Confluence Health ( Site 0061); 🇺🇸 Wenatchee, Washington, United States

Liverpool Hospital ( Site 4006); 🇦🇺 Liverpool, New South Wales, Australia

Monash Health ( Site 4008); 🇦🇺 Clayton, Victoria, Australia

Centro de Pesquisas Clinicas em Oncologia ( Site 0306); 🇧🇷 Cachoeiro de Itapemirim, Espirito Santo, Brazil

Macquarie University ( Site 4007); 🇦🇺 Macquarie University, New South Wales, Australia

Oncocentro Ceara ( Site 0309); 🇧🇷 Fortaleza, Ceara, Brazil

BP - A Beneficencia Portuguesa de São Paulo-Medical Oncology ( Site 0300); 🇧🇷 Sao Paulo, Brazil

A.C. Camargo Cancer Center ( Site 0301); 🇧🇷 Sao Paulo, Brazil

BC Cancer - Vancouver Center ( Site 0120); 🇨🇦 Vancouver, British Columbia, Canada

Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0117); 🇨🇦 Hamilton, Ontario, Canada

Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0; 🇨🇦 Quebec, Canada

Centro Investigacion Cancer James Lind ( Site 0402); 🇨🇱 Temuco, Araucania, Chile

Servicios Medicos Urumed ( Site 0405); 🇨🇱 Rancagua, Lbtdr Gen Bernardo O Higgins, Chile

IC La Serena Research ( Site 0403); 🇨🇱 La Serena, Coquimbo, Chile

Fundacion Arturo Lopez Perez ( Site 0400); 🇨🇱 Santiago, Region M. De Santiago, Chile

Bradfordhill-Clinical Area ( Site 0401); 🇨🇱 Santiago, Region M. De Santiago, Chile

The First Afflilated Hospital of Bengbu Medical College-Urology Surgery ( Site 6041); 🇨🇳 Bengbu, Anhui, China

Peking University First Hospital ( Site 6011); 🇨🇳 Beijing, Beijing, China

Chongqing University Cancer Hospital ( Site 6009); 🇨🇳 Chongqing, Chongqing, China

Cancer Hospital Chinese Academy of Medical Science-Oncology ( Site 6026); 🇨🇳 Beijing, Beijing, China

The First Affiliated Hospital Of Fujian Medical University-Urology ( Site 6038); 🇨🇳 Fuzhou, Fujian, China

SUN YAT-SEN UNIVERSITY CANCER CENTRE ( Site 6003); 🇨🇳 Guangzhou, Guangdong, China

Beijing Cancer hospital-Renal carcinoma and melanoma ( Site 6000); 🇨🇳 Beijing, Beijing, China

The First Affiliated hospital of Xiamen University-Urology ( Site 6001); 🇨🇳 Xiamen, Fujian, China

Guangzhou First People's Hospital ( Site 6007); 🇨🇳 Guangzhou, Guangdong, China

The First Affiliated Hospital of Guangzhou Medical University-Urology ( Site 6036); 🇨🇳 Guangzhou, Guangdong, China

Henan Cancer Hospital-Urology ( Site 6006); 🇨🇳 Zhengzhou, Henan, China

Harbin Medical University Cancer Hospital-urology ( Site 6015); 🇨🇳 Harbin, Heilongjiang, China

Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School-Urology ( S; 🇨🇳 NanJing, Jiangsu, China

Sun Yat-sen Memorial Hospital, Sun Yat-sen University-Urology Surgery ( Site 6005); 🇨🇳 Guangzhou, Guangdong, China

Wuhan Union Hospital ( Site 6002); 🇨🇳 Wuhan, Hubei, China

Xiangya Hospital Central South University ( Site 6034); 🇨🇳 Changsha, Hunan, China

Hunan Cancer Hospital ( Site 6020); 🇨🇳 Changsha, Hunan, China

The Second Affiliated Hospital of Soochow University-Urology ( Site 6025); 🇨🇳 Suzhou, Jiangsu, China

The First Affiliated Hospital of Nanchang University ( Site 6019); 🇨🇳 Nanchang, Jiangxi, China

Jiangxi Provincial Cancer Hospital ( Site 6042); 🇨🇳 Nanchang, Jiangxi, China

The First Affiliated Hospital of Xi'an Jiaotong University ( Site 6014); 🇨🇳 Xi'an, Shaanxi, China

The Second Hospital of Tianjin Medical University ( Site 6032); 🇨🇳 Tianjin, Tianjin, China

Renji Hospital Shanghai Jiao Tong University School of Medicine ( Site 6017); 🇨🇳 Shanghai, Shanghai, China

Tianjin Medical University Cancer Institute and Hospital ( Site 6029); 🇨🇳 Tianjin, Tianjin, China

The First Affiliated Hospital, Zhejiang University ( Site 6024); 🇨🇳 Hangzhou, Zhejiang, China

Shanghai Tenth People's Hospital ( Site 6023); 🇨🇳 Shanghai, Shanghai, China

West China Hospital Sichuan University-Urology Surgery ( Site 6016); 🇨🇳 Cheng Du, Sichuan, China

The First Hospital of Jiaxing ( Site 6033); 🇨🇳 Jiaxing, Zhejiang, China

Ningbo First Hospital-Urology ( Site 6028); 🇨🇳 Ningbo, Zhejiang, China

The First Affiliated Hospital of Wenzhou Medical University-Urology Surgery ( Site 6021); 🇨🇳 Wenzhou, Zhejiang, China

Clinica de la Costa S.A.S. ( Site 0502); 🇨🇴 Barranquilla, Atlantico, Colombia

Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 0505); 🇨🇴 Valledupar, Cesar, Colombia

Instituto Nacional de Cancerología E.S.E. ( Site 0503); 🇨🇴 Bogotá, Distrito Capital De Bogota, Colombia

Administradora Country SA - Clinica del Country ( Site 0504); 🇨🇴 Bogota, Distrito Capital De Bogota, Colombia

Fundacion Cardiovascular de Colombia ( Site 0506); 🇨🇴 Piedecuesta, Santander, Colombia

Oncólogos del Occidente S.A ( Site 0501); 🇨🇴 Pereira, Risaralda, Colombia

Klinicki Bolnicki Centar Zagreb ( Site 3200); 🇭🇷 Zagreb, Grad Zagreb, Croatia

Fakultni nemocnice u sv. Anny v Brne ( Site 2205); 🇨🇿 Brno, Jihomoravsky Kraj, Czechia

Masarykuv onkologicky ustav ( Site 2203); 🇨🇿 Brno, Brno-mesto, Czechia

Klinički Bolnički Centar Split ( Site 3202); 🇭🇷 Split, Splitsko-dalmatinska Zupanija, Croatia

Klinicki bolnicki centar "Sestre milosrdnice" ( Site 3201); 🇭🇷 Zagreb, Zagrebacka Zupanija, Croatia

Nemocnice AGEL Novy Jicin a.s. ( Site 2202); 🇨🇿 Novy Jicin, Moravskoslezsky Kraj, Czechia

Fakultni nemocnice Ostrava ( Site 2208); 🇨🇿 Ostrava, Moravskoslezsky Kraj, Czechia

Odense University Hospital ( Site 1701); 🇩🇰 Odense, Syddanmark, Denmark

Fakultni Thomayerova nemocnice ( Site 2201); 🇨🇿 Praha 4, Czechia

Fakultni nemocnice Olomouc ( Site 2200); 🇨🇿 Olomouc, Czechia

HYKS ( Site 1800); 🇫🇮 Helsinki, Uusimaa, Finland

TYKS ( Site 1802); 🇫🇮 Turku, Varsinais-Suomi, Finland

TAYS ( Site 1801); 🇫🇮 Tampere, Pirkanmaa, Finland

2 LF UK a FN Motol ( Site 2207); 🇨🇿 Praha 5, Czechia

Kuopion Yliopistollinen Sairaala ( Site 1803); 🇫🇮 Kuopio, Pohjois-Savo, Finland

Institut Paoli Calmettes ( Site 1206); 🇫🇷 Marseille, Bouches-du-Rhone, France

CHU Jean Minjoz ( Site 1205); 🇫🇷 Besancon, Doubs, France

Herlev Hospital ( Site 1700); 🇩🇰 Herlev, Hovedstaden, Denmark

Institut Claudius Regaud ( Site 1214); 🇫🇷 Toulouse, Haute-Garonne, France

CHU Angers ( Site 1200); 🇫🇷 Angers, Maine-et-Loire, France

Clinique Ambroise Pare Beuvry ( Site 1213); 🇫🇷 Beuvry, Nord-Pas-de-Calais, France

Gustave Roussy ( Site 1207); 🇫🇷 Villejuif, Val-de-Marne, France

Hopital Tenon ( Site 1212); 🇫🇷 Paris, France

CH Lyon Sud Hospices Civils de Lyon ( Site 1203); 🇫🇷 Pierre Benite, Rhone, France

Helios Kliniken Schwerin GmbH ( Site 1302); 🇩🇪 Schwerin, Mecklenburg-Vorpommern, Germany

Universitaetsklinik fuer Urologie ( Site 1300); 🇩🇪 Tuebingen, Baden-Wurttemberg, Germany

Charite Universitaetsmedizin Berlin ( Site 1301); 🇩🇪 Berlin, Germany

Grupo Angeles SA ( Site 0705); 🇬🇹 Guatemala, Guatemala

Centro Medico Integral de Cancerologia CEMIC ( Site 0701); 🇬🇹 Salcaja, Quetzaltenango, Guatemala

Oncomedica ( Site 0700); 🇬🇹 Guatemala, Guatemala

Sanatorio Nuestra Senora del Pilar ( Site 0702); 🇬🇹 Guatemala, Guatemala

Centro Regional de Sub Especialidades Medicas SA ( Site 0704); 🇬🇹 Quetzaltenango, Guatemala

Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 2308); 🇭🇺 Kecskemét, Bacs-Kiskun, Hungary

Medi-K Cayala ( Site 0703); 🇬🇹 Guatemala, Guatemala

Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház ( Site 2300); 🇭🇺 Szolnok, Jasz-Nagykun-Szolnok, Hungary

Bekes Megyei Kozponti Korhaz - Pandy Kalman Tagkorhaza ( Site 2309); 🇭🇺 Gyula, Bekes, Hungary

Markusovszky Egyetemi Oktatokorhaz ( Site 2303); 🇭🇺 Szombathely, Vas, Hungary

Orszagos Onkologiai Intezet ( Site 2304); 🇭🇺 Budapest, Hungary

Tallaght University Hospital ( Site 6100); 🇮🇪 Dublin, Ireland

Azienda Ospedaliero - Universitaria Policlinico di Modena ( Site 1404); 🇮🇹 Modena, Emilia-Romagna, Italy

Debreceni Egyetem Klinikai Kozpont ( Site 2301); 🇭🇺 Debrecen, Hungary

Beaumont Hospital ( Site 6101); 🇮🇪 Dublin, Ireland

Ospedale San Raffaele-Oncologia Medica ( Site 1417); 🇮🇹 Milano, Lombardia, Italy

Fondazione Policlinico Universitario A. Gemelli ( Site 1414); 🇮🇹 Rome, Roma, Italy

Azienda Ospedaliera Policlinico di Bari ( Site 1411); 🇮🇹 Bari, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 1409); 🇮🇹 Milano, Italy

Istituto Nazionale Tumori Fondazione Pascale ( Site 1412); 🇮🇹 Napoli, Italy

Azienda Ospedaliera S. Maria di Terni ( Site 1410); 🇮🇹 Terni, Italy

Fujita Health University ( Site 5003); 🇯🇵 Toyoake, Aichi, Japan

National Cancer Center Hospital East ( Site 5000); 🇯🇵 Kashiwa, Chiba, Japan

Chiba cancer center ( Site 5021); 🇯🇵 Chiba-shi, Chiba, Japan

Ehime University Hospital ( Site 5020); 🇯🇵 Toon, Ehime, Japan

Sapporo Medical University Hospital ( Site 5008); 🇯🇵 Sapporo, Hokkaido, Japan

Kanagawa cancer center ( Site 5016); 🇯🇵 Yokohama, Kanagawa, Japan

Hokkaido University Hospital ( Site 5013); 🇯🇵 Sapporo, Hokkaido, Japan

Nara Medical University Hospital ( Site 5002); 🇯🇵 Kashihara, Nara, Japan

Saitama Medical University International Medical Center ( Site 5015); 🇯🇵 Hidaka-city, Saitama, Japan

Hamamatsu University School of Medicine University Hospital ( Site 5004); 🇯🇵 Hamamatsu, Shizuoka, Japan

Kindai University Hospital- Osakasayama Campus-Urology ( Site 5010); 🇯🇵 Osakasayama, Osaka, Japan

Osaka University Hospital ( Site 5012); 🇯🇵 Suita, Osaka, Japan

Tokyo Medical And Dental University Medical Hospital-Urology ( Site 5009); 🇯🇵 Bunkyō, Tokyo, Japan

Kyushu University Hospital ( Site 5005); 🇯🇵 Fukuoka, Japan

Toyama University Hospital ( Site 5014); 🇯🇵 Toyoma, Toyama, Japan

Toranomon Hospital ( Site 5001); 🇯🇵 Minato-ku, Tokyo, Japan

Kumamoto University ( Site 5022); 🇯🇵 Kumamoto, Japan

Okayama University Hospital ( Site 5017); 🇯🇵 Okayama, Japan

Niigata University Medical & Dental Hospital ( Site 5024); 🇯🇵 Niigata, Japan

Tokushima University Hospital-Department of Urology ( Site 5019); 🇯🇵 Tokushima, Japan

Tokyo Women's Medical University Adachi Medical Center ( Site 5023); 🇯🇵 Tokyo, Japan

Keio university hospital ( Site 5011); 🇯🇵 Tokyo, Japan

Chungnam National University Hospital ( Site 4205); 🇰🇷 Daejeon, Taejon-Kwangyokshi, Korea, Republic of

National Cancer Center ( Site 4202); 🇰🇷 Goyang-si, Kyonggi-do, Korea, Republic of

Hospital Kuala Lumpur ( Site 4301); 🇲🇾 Kuala Lumpur, Malaysia

Institut Kanser Negara - National Cancer Institute ( Site 4302); 🇲🇾 Putrajaya, Wilayah Persekutuan Putrajaya, Malaysia

Universiti Malaya Medical Centre ( Site 4300); 🇲🇾 Kuala Lumpur, Malaysia

I CAN Oncology SA de SV ( Site 0601); 🇲🇽 Monterrey, Nuevo Leon, Mexico

Instituto Nacional de Cancerologia ( Site 0602); 🇲🇽 Cdmx, Mexico

Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 0610); 🇲🇽 Guadalajara, Jalisco, Mexico

Akershus universitetssykehus ( Site 2000); 🇳🇴 Lorenskog, Akershus, Norway

Helse Bergen HF - Haukeland Universitetssykehus ( Site 2002); 🇳🇴 Bergen, Hordaland, Norway

Sykehuset Østfold HF Kalnes ( Site 2003); 🇳🇴 Gralum, Ostfold, Norway

Oslo Universitetssykehus Radiumhospitalet ( Site 2001); 🇳🇴 Oslo, Norway

Soerlandet sykehus HF Kristiansand ( Site 2007); 🇳🇴 Kristiansand, Aust-Agder, Norway

St. Olavs Hospital HF ( Site 2005); 🇳🇴 Trondheim, Sor-Trondelag, Norway

Manila Doctors Hospital ( Site 4601); 🇵🇭 Manila, National Capital Region, Philippines

The Medical City ( Site 4602); 🇵🇭 Pasig City, National Capital Region, Philippines

Cardinal Santos Medical Center ( Site 4603); 🇵🇭 San Juan, National Capital Region, Philippines

Radomskie Centrum Onkologii ( Site 2418); 🇵🇱 Radom, Mazowieckie, Poland

Luxmed Onkologia sp. z o. o. ( Site 2412); 🇵🇱 Warszawa, Mazowieckie, Poland

Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 2420); 🇵🇱 Bydgoszcz, Kujawsko-pomorskie, Poland

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 2405); 🇵🇱 Warszawa, Mazowieckie, Poland

Przychodnia Lekarska KOMED ( Site 2419); 🇵🇱 Konin, Wielkopolskie, Poland

Szpital Wojewodzki im. Mikolaja Kopernika ( Site 2407); 🇵🇱 Koszalin, Zachodniopomorskie, Poland

Spitalul Judetean de Urgenta Alba Iulia ( Site 2502); 🇷🇴 Alba Iulia, Alba, Romania

Policlinica Oncomed SRL ( Site 2506); 🇷🇴 Timisoara, Timis, Romania

S.C.Focus Lab Plus S.R.L ( Site 2503); 🇷🇴 Bucuresti, Romania

Altay Regional Oncology Dispensary ( Site 2610); 🇷🇺 Barnaul, Altayskiy Kray, Russian Federation

Ivanovo Regional Oncology Dispensary ( Site 2615); 🇷🇺 Ivanovo, Ivanovskaya Oblast, Russian Federation

Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 2609); 🇷🇺 Krasnoyarsk, Krasnoyarskiy Kray, Russian Federation

The Loginov Moscow Clinical Scientific Center ( Site 2604); 🇷🇺 Moscow, Moskva, Russian Federation

Moscow Oncological Clinical Dispensary #1 ( Site 2619); 🇷🇺 Moscow, Moskva, Russian Federation

Nizhniy Novgorod Region Oncology Dispensary ( Site 2621); 🇷🇺 Nizhniy Novgorod, Nizhegorodskaya Oblast, Russian Federation

FBHI Privolzhsky District Medical Center of the FMBA ( Site 2611); 🇷🇺 Nizhny Novgorod, Nizhegorodskaya Oblast, Russian Federation

Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 2617); 🇷🇺 Saint Petersburg, Sankt-Peterburg, Russian Federation

Klinicki centar Srbije. ( Site 3333); 🇷🇸 Belgrade, Beograd, Serbia

Klinicki centar Nis ( Site 3322); 🇷🇸 Nis, Nisavski Okrug, Serbia

City clinical oncological dispensary ( Site 2605); 🇷🇺 Sankt-Petersburg, Sankt-Peterburg, Russian Federation

Institut za onkologiju Vojvodine ( Site 3311); 🇷🇸 Sremska Kamenica, Sremski Okrug, Serbia

Cancer Care Langenhoven Drive Oncology Centre ( Site 3009); 🇿🇦 Port Elizabeth, Eastern Cape, South Africa

Univ. Pretoria and Steve Biko Academic Hospitals ( Site 3002); 🇿🇦 Pretoria, Gauteng, South Africa

Sandton Oncology Medical Group PTY LTD ( Site 3000); 🇿🇦 Johannesburg, Gauteng, South Africa

Mary Potter Oncology Centre, Little Company of Mary Hospital ( Site 3001); 🇿🇦 Pretoria, Gauteng, South Africa

Life Wilgers Hospital ( Site 3004); 🇿🇦 Pretoria, Gauteng, South Africa

Vaal Triangle Oncology Centre ( Site 3010); 🇿🇦 Vereeniging, Gauteng, South Africa

Institut Català d'Oncologia (ICO) - Girona ( Site 1500); 🇪🇸 Girona, Gerona, Spain

Groote Schuur Hospital ( Site 3011); 🇿🇦 Cape Town, Western Cape, South Africa

Instituto Catalan de Oncologia - ICO ( Site 1502); 🇪🇸 L Hospitalet De Llobregat, Barcelona, Spain

Cape Town Oncology Trials Pty Ltd ( Site 3006); 🇿🇦 Kraaifontein, Western Cape, South Africa

Hospital Universitario Marques de Valdecilla ( Site 1501); 🇪🇸 Santander, Cantabria, Spain

Karolinska Universitetssjukhuset Solna ( Site 2100); 🇸🇪 Stockholm, Stockholms Lan, Sweden

Akademiska Sjukhuset ( Site 2105); 🇸🇪 Uppsala, Uppsala Lan, Sweden

Lanssjukhuset Ryhov ( Site 2103); 🇸🇪 Jonkoping, Jonkopings Lan, Sweden

Taichung Veterans General Hospital ( Site 4403); 🇨🇳 Taichung, Taiwan

Sahlgrenska Universitetssjukhuset ( Site 2102); 🇸🇪 Goteborg, Vastra Gotalands Lan, Sweden

Norrlands Universitetssjukhus ( Site 2106); 🇸🇪 Umea, Vasterbottens Lan, Sweden

Chang Gung Medical Foundation. Kaohsiung Branch ( Site 4405); 🇨🇳 Kaohsiung, Taiwan

National Taiwan University Hospital ( Site 4401); 🇨🇳 Taipei, Taiwan

Taipei Veterans General Hospital ( Site 4402); 🇨🇳 Taipei, Taiwan

Chang Gung Medical Foundation-Linkou Branch-Urology ( Site 4406); 🇨🇳 Taoyuan, Taiwan

Ramathibodi Hospital. ( Site 4500); 🇹🇭 Bangkok, Krung Thep Maha Nakhon, Thailand

Hacettepe Universitesi Tıp Fakultesi ( Site 2903); 🇹🇷 Ankara, Turkey

Trakya University Medical Faculty Balkan Oncology Hospital ( Site 2906); 🇹🇷 Edirne, Turkey

Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 2900); 🇹🇷 Istanbul, Turkey

TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 2901); 🇹🇷 Istanbul, Turkey

Cherkasy Regional Oncology Dispensary ( Site 2704); 🇺🇦 Cherkasy, Cherkaska Oblast, Ukraine

Ege Universitesi Tip Fakultesi Hastanesi ( Site 2904); 🇹🇷 Izmir, Turkey

Clinical oncology dispensary of Dnipro ( Site 2700); 🇺🇦 Dnipro, Dnipropetrovska Oblast, Ukraine

Ivano-Frankivsk Regional Oncology Clinical Dispensary ( Site 2711); 🇺🇦 Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine

Ivano-Frankivsk Regional Hospital-Urology department ( Site 2707); 🇺🇦 Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine

Regional Oncology Center of Kharkiv ( Site 2708); 🇺🇦 Kharkiv, Kharkivska Oblast, Ukraine

Reg. Clinical Center of Urology and Nephrology n.a. V. I. Shapoval ( Site 2715); 🇺🇦 Kharkiv, Kharkivska Oblast, Ukraine

Kyiv City Clinical Oncology Center ( Site 2706); 🇺🇦 Kyiv, Kyivska Oblast, Ukraine

Addenbrookes Hospital ( Site 3110); 🇬🇧 Cambridge, Cambridgeshire, United Kingdom

Mount Vernon Cancer Centre ( Site 3101); 🇬🇧 Northwood, London, City Of, United Kingdom

Dartmouth Hitchcock Medical Center ( Site 0075); 🇺🇸 Lebanon, New Hampshire, United States

University of Tennessee Medical Center Knoxville ( Site 0019); 🇺🇸 Knoxville, Tennessee, United States

Korea University Anam Hospital ( Site 4206); 🇰🇷 Seoul, Korea, Republic of

Asan Medical Center ( Site 4203); 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center ( Site 4200); 🇰🇷 Seoul, Korea, Republic of

Seoul National University Hospital ( Site 4201); 🇰🇷 Seoul, Korea, Republic of

Advent Health Hematology & Oncology ( Site 0003); 🇺🇸 Orlando, Florida, United States

Norton Cancer Institute - St. Matthews ( Site 0065); 🇺🇸 Louisville, Kentucky, United States

Ochsner Medical Center ( Site 0049); 🇺🇸 New Orleans, Louisiana, United States

Ralph H. Johnson VA Center ( Site 0073); 🇺🇸 Charleston, South Carolina, United States