A Study of Belzutifan (MK-6482) Versus Everolimus in Participants With Advanced Renal Cell Carcinoma (MK-6482-005)

Phase 3

Active, not recruiting

• Conditions: Carcinoma, Renal Cell
• Interventions: Drug: Belzutifan; Drug: Everolimus

• Registration Number: NCT04195750
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

The primary objective of this study is to compare belzutifan to everolimus with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR) and to compare everolimus with respect to overall survival (OS). The hypothesis is that belzutifan is superior to everolimus with respect to PFS and OS.

Detailed Description

Per protocol, all participants enrolled in the Safety Run-In were not randomized and not included in the protocol-specified analyses for any of the outcome measures.

Study Timeline

• Study First Submitted: 2019-12-10
• Study First Submitted QC: 2019-12-10
• Study First Posted: 2019-12-12
• Study Start: 2020-02-27
• Primary Completion: 2024-04-15
• Status Verified: 2025-04
• Results First Submitted: 2025-04-09
• Results First Submitted QC: 2025-04-09
• Last Update Submitted: 2025-04-09
• Results First Posted: 2025-04-29
• Last Update Posted: 2025-04-29
• Study Completion: 2026-09-17

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 755

Inclusion Criteria

• Has unresectable, locally advanced or metastatic clear cell renal cell carcinoma (RCC)
• Has had disease progression on or after having received systemic treatment for locally advanced or metastatic RCC with both Programmed cell death 1 ligand 1 (PD-1/L1) checkpoint inhibitor and a vascular endothelial growth factor - tyrosine kinase inhibitor (VEGF-TKI) in sequence or in combination
• Has received no more than 3 prior systemic regimens for locally advanced or metastatic RCC
• A male participant is eligible to participate if he is abstinent from heterosexual intercourse or agrees to use contraception during the intervention period and for at least 7 days after the last dose of study intervention
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a woman of childbearing potential (WOCBP) OR a WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 30 days after the last dose of study intervention for those randomized to belzutifan and for at least 8 weeks after the last dose of study intervention for those randomized to everolimus
• The participant (or legally acceptable representative if applicable) has provided documented informed consent for the study
• Has adequate organ function

Exclusion Criteria

• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. (Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ [e.g., breast carcinoma, cervical cancer in situ] that have undergone potentially curative therapy are not excluded)
• Has known central nervous system (CNS) metastases and/or carcinomatous meningitis. (Participants with previously treated brain metastases may participate provided they are radiologically stable for at least 4 weeks (28 days) by repeat imaging)
• Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study medication administration, or New York Heart Association Class III or IV congestive heart failure. (Medically controlled arrhythmia stable on medication is permitted)
• Has poorly controlled hypertension defined as systolic blood pressure (SBP) ≥150 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg
• Has moderate to severe hepatic impairment (Child-Pugh B or C)
• Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study
• Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption)
• Has known hypersensitivity or allergy to the active pharmaceutical ingredient or any component of the study intervention (belzutifan or everolimus) formulations
• Has received prior treatment with belzutifan or another hypoxia inducible factor 2α (HIF-2α inhibitor)
• Has received prior treatment with everolimus or any other specific or selective target of rapamycin complex 1 (TORC1)/ phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT) inhibitor (e.g., temsirolimus) in the advanced disease setting
• Has received any type of systemic anticancer antibody (including investigational antibody) within 4 weeks before randomization
• Has received prior radiotherapy within 2 weeks prior to randomization
• Has had major surgery within 3 weeks prior to randomization
• Has received a live vaccine within 30 days prior to randomization. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines are live attenuated vaccines and are not allowed
• Is currently receiving either strong (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of the study
• Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate (e.g., bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued for the duration of the study
• Is currently participating in a study of an investigational agent or is currently using an investigational device
• Has an active infection requiring systemic therapy
• Has active bacillus tuberculosis (TB)
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization
• Has a known history of human immunodeficiency virus (HIV) infection. (Testing for HIV at screening is only required if mandated by local health authority
• Has a known history of Hepatitis B virus (HBV) (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (HCV) (defined as HCV ribonucleic acid [RNA] [qualitative] is detected) infection

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Belzutifan	Belzutifan	Randomized participants received 120 mg of belzutifan orally once daily (QD), until disease progression or discontinuation.
Everolimus	Everolimus	Randomized participants received 10 mg of Everolimus orally QD, until disease progression or discontinuation.
Safety Run-In	Belzutifan	Non-Randomized participants enrolled into the Safety Run-in received up to 120 mg of belzutifan QD.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)	Up to approximately 39 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 blinded independent central review is presented here.
Overall Survival (OS)	Up to approximately 49 months	OS is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR	Up to approximately 31 months	ORR is defined as the percentage of participants who have a complete response (CR: Disappearance of all target lesions) or a 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 blinded independent central review based on RECIST 1.1 is presented here.
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR	Up to approximately 49 months	For participants who demonstrate a confirmed complete response (CR: Disappearance of all target lesions) or confirmed partial response (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 disease progression or death. The DOR as assessed by blinded independent central review is presented here. The Median DOR was analyzed by the Kaplan-Meier method for censored data.
Number of Participants Who Experience One or More Adverse Events (AEs)	Up to approximately 78 months	An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Number of Participants Who Discontinue Study Treatment Due to an AE	Up to approximately 78 months	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The number of participants who discontinue study treatment due to an AE will be presented.
Time to True Deterioration (TTD) in Health-Related Quality-of-Life (HRQoL) Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 29 and 30 Combined Score	Up to approximately 39 months	The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent), then summed. Summed raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. TTD was defined as the time from baseline to the first onset of a ≥10-point decrease with confirmation by the subsequent visit of a ≥10-point decrease in Items 29 and 30 scale scores. If the first deterioration is at the last PRO assessment timepoint at the time of analysis, then no confirmation is required. A longer TTD indicates a better outcome. TTD is reported based on the product-limit (Kaplan-Meier) method for censored data.
TTD in Physical Functioning Using the EORTC QLQ-C30 Items 1- 5 Score	Up to approximately 39 months	The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much), then summed. Summed raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. TTD was defined as the time from baseline to the first onset of a ≥10-point decrease with confirmation by the subsequent visit of a ≥10-point decrease in physical functioning Items 1 to 5 scale scores. If the first deterioration is at the last PRO assessment timepoint at the time of analysis, then no confirmation is required. A longer TTD indicates a better outcome. TTD is reported based on the product-limit (Kaplan-Meier) method for censored data.
TTD in Disease Symptoms Using the Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease-related Symptoms (FKSI-DRS) Items 1-9 Score	Up to approximately 39 months	The FKSI-DRS was a questionnaire that asked the participant to rate 9 kidney cancer-related symptoms: lack of energy, fatigue, weight loss, pain, bone pain, shortness of breath, cough, fever, or blood in the urine. Each item was scored on a 5-point scale (0=not at all to 4=very much). FKSI-DRS total score ranged from 0 (most severe symptoms) to 36 (no symptoms) with a higher score indicating a better outcome. TTD was defined as the time to first onset of a ≥3-point decrease in symptom score from baseline with confirmation by the subsequent visit of a ≥3-point deterioration from baseline under right-censoring rule. If the first deterioration is at the last PRO assessment timepoint at the time of analysis, then no confirmation is required. A longer TTD indicates a better outcome. TTD is reported based on the product-limit (Kaplan-Meier) method for censored data.
Change From Baseline to Week 17 in the HRQoL Using the EORTC QLQ-C30 Items 29 and 30 Combined Score	Baseline (Day 1) and week 17	The EORTC-QLQ-C30 is a 30-item questionnaire to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question "How would you rate your overall health during the past week?" (Item 29) and the Quality of Life (QoL) question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100; a higher score indicating a better overall outcome. Change from baseline to Week 17 in EORTC QLQ-C30 Items 29 and 30 combined scores was calculated based on a constrained longitudinal data analysis (cLDA) model with scores as response variable with covariates for treatment by time interaction, stratification factors (IMDC Risk Category, and Number of Prior VEGF/VEGF-Receptor Targeted Therapies for RCC) as covariates.
Change From Baseline to Week 17 in Physical Functioning Using the EORTC QLQ-C30 Items 1- 5 Score	Baseline (Day 1) and week 17	The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much), then summed. Summed raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. The change from baseline to Week 17 in physical functioning (EORTC QLQ-C30 Items 1-5) score was calculated based on a constrained longitudinal data analysis (cLDA) model with scores as response variable with covariates for treatment by time interaction, stratification factors (IMDC Risk Category, and Number of Prior VEGF/VEGF-Receptor Targeted Therapies for RCC) as covariates.
Change From Baseline to Week 17 in Disease Symptoms Using the FKSI-DRS Items 1-9 Score	Baseline (Day 1) and week 17	The FKSI-DRS was a questionnaire that asked the participant to rate 9 kidney cancer-related symptoms: lack of energy, fatigue, weight loss, pain, bone pain, shortness of breath, cough, fever, or blood in the urine. Each item was scored on a 5-point scale (0=not at all to 4=very much). FKSI-DRS total score ranged from 0 (most severe symptoms) to 36 (no symptoms) with a higher score indicating a better outcome. The change from baseline to Week 17 in Disease Symptoms using the FKSI-DRS Items 1-9 score was calculated based on a constrained longitudinal data analysis (cLDA) model with the PRO scores as response variable with covariates for treatment by time interaction, stratification factors (IMDC Risk Category, and Number of Prior VEGF/VEGF-Receptor Targeted Therapies for RCC) as covariates.
Change From Baseline to Week 17 in Visual Analogue Scale (VAS) Score on the European Quality of Life 5 Dimension, 5-level Questionnaire (EQ-5D-5L) Health Utility Score	Baseline (Day 1) and week 17	The EQ-5D-5L questionnaire assesses 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/ depression. Each dimension has 5 response options that reflect increasing levels of difficulty, which are coded on a scale from 1 (no problems) to 5 (extreme problems). The VAS is a component of EQ-5D-5L that asks participants to rate their overall health on a vertical visual analogue scale, with the scale's ends labelled 'The best health you can imagine' (equivalent to a score of 0) and 'The worst health you can imagine' (equivalent to a score of 100). The change from baseline to Week 17 in Health Utility using the EQ-5D-5L VAS score was calculated based on a constrained longitudinal data analysis (cLDA) model with the PRO scores as response variable with covariates for treatment by time interaction, stratification factors (IMDC Risk Category, and Number of Prior VEGF/VEGF-Receptor Targeted Therapies for RCC) as covariates.

Trial Locations

Locations (172)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 1514); 🇺🇸 Baltimore, Maryland, United States

The University of Chicago Medical Center ( Site 1539); 🇺🇸 Chicago, Illinois, United States

Cleveland Clinic ( Site 1504); 🇺🇸 Cleveland, Ohio, United States

TYKS T-sairaala Syopatautien pkl ( Site 0301); 🇫🇮 Turku, Varsinais-Suomi, Finland

Bekes Megyei Kozponti Korhaz - Pandy Kalman Tagkorhaza ( Site 0505); 🇭🇺 Gyula, Bekes, Hungary

Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Okta-Klinikai Onkológiai és Sugárterápiás Ce; 🇭🇺 Miskolc, Borsod-Abauj-Zemplen, Hungary

Centre Francois Baclesse ( Site 0360); 🇫🇷 Caen, Calvados, France

Debreceni Egyetem Klinikai Kozpont ( Site 0504); 🇭🇺 Debrecen, Hungary

Zala Megyei Szent Rafael Korhaz ( Site 0509); 🇭🇺 Zalaegerszeg, Hungary

Taichung Veterans General Hospital ( Site 1105); 🇨🇳 Taichung, Taiwan

BC Cancer - Vancouver Center ( Site 0155); 🇨🇦 Vancouver, British Columbia, Canada

Beth Israel Deaconess Medical Center ( Site 1501); 🇺🇸 Boston, Massachusetts, United States

Oncology Hematology Care, Inc. ( Site 1524); 🇺🇸 Cincinnati, Ohio, United States

Henry Joyce Cancer Clinic ( Site 1544); 🇺🇸 Nashville, Tennessee, United States

Centro Investigación del Cáncer James Lind ( Site 0004); 🇨🇱 Temuco, Araucania, Chile

Abramson Cancer Center ( Site 1525); 🇺🇸 Philadelphia, Pennsylvania, United States

Dana Farber Cancer Institute ( Site 1505); 🇺🇸 Boston, Massachusetts, United States

Fakultni nemocnice Kralovske Vinohrady ( Site 0102); 🇨🇿 Praha 10, Czechia

Hospital de Clinicas de Porto Alegre ( Site 1655); 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 1709); 🇨🇴 Valledupar, Cesar, Colombia

Fundacion Centro de Investigacion Clinica CIC ( Site 1703); 🇨🇴 Medellin, Antioquia, Colombia

Administradora Country SA - Clinica del Country ( Site 1701); 🇨🇴 Bogota, Distrito Capital De Bogota, Colombia

Texas Oncology-Austin Central ( Site 1533); 🇺🇸 Austin, Texas, United States

Instituto de Cancer e Transplante de Curitiba ICTR ( Site 1650); 🇧🇷 Curitiba, Parana, Brazil

Bradfordhill ( Site 0003); 🇨🇱 Santiago, Region M. De Santiago, Chile

Texas Oncology, P.A.-Dallas ( Site 1534); 🇺🇸 Dallas, Texas, United States

St. Vincent Frontier Cancer Center ( Site 1549); 🇺🇸 Billings, Montana, United States

Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 1702); 🇨🇴 Bogota, Cundinamarca, Colombia

Fox Chase Cancer Center ( Site 1506); 🇺🇸 Philadelphia, Pennsylvania, United States

Centre Alexis Vautrin Institut de Cancerologie de Lorraine ( Site 0356); 🇫🇷 Vandoeuvre les Nancy, Meurthe-et-Moselle, France

Massachusetts General Hospital ( Site 1558); 🇺🇸 Boston, Massachusetts, United States

Fakultni Thomayerova nemocnice ( Site 0107); 🇨🇿 Praha 4, Czechia

Centro Avancado de Tratamento Oncologico ( Site 1657); 🇧🇷 Belo Horizonte, Minas Gerais, Brazil

Universitaetsklinikum Essen ( Site 0401); 🇩🇪 Essen, Nordrhein-Westfalen, Germany

Liga Norte Riograndense Contra o Cancer ( Site 1651); 🇧🇷 Natal, Rio Grande Do Norte, Brazil

Universitatsklinikum Hamburg-Eppendorf ( Site 0408); 🇩🇪 Hamburg, Germany

Kuopion Yliopistollinen Sairaala ( Site 0304); 🇫🇮 Kuopio, Pohjois-Savo, Finland

CHU Besancon - Hopital Jean Minjoz ( Site 0351); 🇫🇷 Besancon, Doubs, France

Institut de Cancerologie du Gard - CHU Caremeau ( Site 0352); 🇫🇷 Nimes, Gard, France

Tampereen yliopistollinen sairaala ( Site 0300); 🇫🇮 Tampere, Pirkanmaa, Finland

Orszagos Onkologiai Intezet ( Site 0503); 🇭🇺 Budapest, Hungary

Fakultni nemocnice Olomouc ( Site 0104); 🇨🇿 Olomouc, Czechia

Universitaetsklinikum Magdeburg A.o.R. ( Site 0404); 🇩🇪 Magdeburg, Sachsen-Anhalt, Germany

Saitama Medical University International Medical Center ( Site 1012); 🇯🇵 Hidaka-city, Saitama, Japan

Universitaetsklinik fuer Urologie ( Site 0405); 🇩🇪 Tuebingen, Baden-Wurttemberg, Germany

Gustave Roussy ( Site 0353); 🇫🇷 Villejuif, Val-de-Marne, France

Kindai University Hospital- Osakasayama Campus-Urology ( Site 1011); 🇯🇵 Osakasayama, Osaka, Japan

Chang Gung Medical Foundation - Kaohsiung ( Site 1104); 🇨🇳 Kaohsiung, Taiwan

Norrlands Universitetssjukhus ( Site 1856); 🇸🇪 Umeå, Vasterbottens Lan, Sweden

National Taiwan University Hospital ( Site 1100); 🇨🇳 Taipei, Taiwan

Russian Scientific Center of Radiology and Surgical Technologies ( Site 1153); 🇷🇺 St. Petersburg, Sankt-Peterburg, Russian Federation

Semmelweis Egyetem ( Site 0501); 🇭🇺 Budapest, Hungary

Taipei Veterans General Hospital ( Site 1101); 🇨🇳 Taipei, Taiwan

Osaka University Hospital ( Site 1006); 🇯🇵 Suita, Osaka, Japan

Akershus universitetssykehus ( Site 0851); 🇳🇴 Lorenskog, Akershus, Norway

Severance Hospital Yonsei University Health System ( Site 1202); 🇰🇷 Seoul, Korea, Republic of

Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 1151); 🇷🇺 Krasnoyarsk, Krasnoyarskiy Kray, Russian Federation

Chang Gung Medical Foundation-Linkou Branch-Urology ( Site 1106); 🇨🇳 Taoyuan, Taiwan

Laenssjukhuset Ryhov ( Site 1853); 🇸🇪 Jönköping, Jonkopings Lan, Sweden

Chungnam National University Hospital ( Site 1205); 🇰🇷 Daejeon, Taejon-Kwangyokshi, Korea, Republic of

SBIH City clinical hospital named after D.D. Pletniov ( Site 1160); 🇷🇺 Moscow, Moskva, Russian Federation

Helse Bergen HF - Haukeland Universitetssykehus ( Site 0854); 🇳🇴 Bergen, Hordaland, Norway

Toranomon Hospital ( Site 1004); 🇯🇵 Tokyo, Japan

Russian Scientific Center of Roentgenoradiology ( Site 1155); 🇷🇺 Moscow, Moskva, Russian Federation

Ankara Universitesi Tip Fakultesi ( Site 1311); 🇹🇷 Ankara, Turkey

City clinical oncological dispensary ( Site 1154); 🇷🇺 Sankt-Petersburg, Sankt-Peterburg, Russian Federation

Asan Medical Center ( Site 1200); 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center ( Site 1201); 🇰🇷 Seoul, Korea, Republic of

First Moscow State Medical University n.a. I.M.Sechenov ( Site 1163); 🇷🇺 Moscow, Moskva, Russian Federation

Hospital General Universitario 12 de Octubre ( Site 1252); 🇪🇸 Madrid, Madrid, Comunidad De, Spain

National Cheng Kung University Hospital ( Site 1103); 🇨🇳 Tainan, Taiwan

Gazi Universitesi Tip Fakultesi ( Site 1308); 🇹🇷 Ankara, Turkey

Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 1303); 🇹🇷 Istanbul, Turkey

Instituto Catalan de Oncologia - ICO ( Site 1251); 🇪🇸 L Hospitalet De Llobregat, Barcelona, Spain

Hospital Ramon y Cajal ( Site 1253); 🇪🇸 Madrid, Spain

Cambridge University Hospitals NHSFT ( Site 1405); 🇬🇧 Cambridge, Cambridgeshire, United Kingdom

MI Dnipr Regional Clinical Hospital named after I.I. Mechnikov ( Site 1453); 🇺🇦 Dnipropetrovsk, Dnipropetrovska Oblast, Ukraine

The Beatson West of Scotland Cancer Centre ( Site 1402); 🇬🇧 Glasgow, Glasgow City, United Kingdom

Kyiv City Clinical Oncology Center ( Site 1450); 🇺🇦 Kyiv, Kyivska Oblast, Ukraine

MI Precarpathian Clinical Oncology Center ( Site 1452); 🇺🇦 Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine

Royal Marsden Hospital Sutton-Surrey ( Site 1411); 🇬🇧 Sutton, Surrey, United Kingdom

Royal Marsden NHS Foundation Trust ( Site 1403); 🇬🇧 London, London, City Of, United Kingdom

Aarhus University Hospital Skejby ( Site 0250); 🇩🇰 Aarhus, Midtjylland, Denmark

Malmo Universitetssjukhus ( Site 1851); 🇸🇪 Malmo, Skane Lan, Sweden

Karolinska Universitetssjukhuset Solna ( Site 1850); 🇸🇪 Stockholm, Stockholms Lan, Sweden

Hacettepe Universitesi Tip Fakultesi ( Site 1300); 🇹🇷 Ankara, Turkey

Trakya University Medical Faculty Balkan Oncology Hospital ( Site 1302); 🇹🇷 Edirne, Turkey

Ege Universitesi Tip Fakultesi Hastanesi ( Site 1304); 🇹🇷 Izmir, Turkey

Centre Hospitalier Lyon Sud ( Site 0354); 🇫🇷 Pierre Benite, Rhone, France

CHU de Bordeaux Hop St ANDRE ( Site 0359); 🇫🇷 Bordeaux, Aquitaine, France

Sapporo Medical University Hospital ( Site 1008); 🇯🇵 Sapporo, Hokkaido, Japan

Hamamatsu University Hospital ( Site 1005); 🇯🇵 Hamamatsu, Shizuoka, Japan

Toyama University Hospital ( Site 1013); 🇯🇵 Toyoma, Toyama, Japan

Yamaguchi University Hospital ( Site 1018); 🇯🇵 Ube, Yamaguchi, Japan

Kyushu University Hospital ( Site 1007); 🇯🇵 Fukuoka, Japan

Hiroshima University Hospital-Hiroshima University Hospital ( Site 1019); 🇯🇵 Hiroshima, Japan

Niigata University Medical & Dental Hospital ( Site 1022); 🇯🇵 Niigata, Japan

Tokushima University Hospital-Department of Urology ( Site 1017); 🇯🇵 Tokushima, Japan

Keio University Hospital ( Site 1002); 🇯🇵 Tokyo, Japan

The Christie NHS Foundation Trust ( Site 1401); 🇬🇧 Manchester, United Kingdom

Imperial Healthcare NHS Trust Charing Cross Hospital ( Site 1409); 🇬🇧 London, London, City Of, United Kingdom

Juravinski Cancer Centre ( Site 0154); 🇨🇦 Hamilton, Ontario, Canada

Nova Scotia Health Authority QEII-HSC ( Site 0150); 🇨🇦 Halifax, Nova Scotia, Canada

Sunnybrook Research Institute ( Site 0153); 🇨🇦 Toronto, Ontario, Canada

Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0151); 🇨🇦 Montreal, Quebec, Canada

CHUQ-Univ Laval-Hotel Dieu de Quebec ( Site 0152); 🇨🇦 Quebec, Canada

Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 1653); 🇧🇷 Sao Paulo, Brazil

Universitaetsmedizin Berlin ( Site 0400); 🇩🇪 Berlin, Germany

Universitaetsklinikum Jena ( Site 0402); 🇩🇪 Jena, Thuringen, Germany

Masarykuv onkologicky ustav ( Site 0105); 🇨🇿 Brno, Brno-mesto, Czechia

John Theurer Cancer Center at Hackensack University Medical Center ( Site 1513); 🇺🇸 Hackensack, New Jersey, United States

University of California San Diego Moores Cancer Center ( Site 1546); 🇺🇸 La Jolla, California, United States

UCHealth Highlands Ranch Hospital ( Site 1560); 🇺🇸 Highlands Ranch, Colorado, United States

St Joseph Heritage Healthcare ( Site 1531); 🇺🇸 Santa Rosa, California, United States

University of Rochester Medical Center ( Site 1543); 🇺🇸 Rochester, New York, United States

Sibley Memorial Hospital ( Site 1559); 🇺🇸 Washington, District of Columbia, United States

Northwest Georgia Oncology Centers PC ( Site 1520); 🇺🇸 Marietta, Georgia, United States

Hattiesburg Clinic ( Site 1509); 🇺🇸 Hattiesburg, Mississippi, United States

Oklahoma Cancer Specialists and Research Institute, LLC ( Site 1523); 🇺🇸 Tulsa, Oklahoma, United States

Fondazione Salvatore Maugeri clinica del lavoro ( Site 0600); 🇮🇹 Pavia, Italy

Oncologos del Occidente S.A. ( Site 1708); 🇨🇴 Pereira, Risaralda, Colombia

Azienda Ospedaliera Santa Maria ( Site 0602); 🇮🇹 Terni, Italy

Fakultni nemocnice Hradec Kralove ( Site 0106); 🇨🇿 Hradec Kralove, Czechia

Fakultni nemocnice Ostrava ( Site 0103); 🇨🇿 Ostrava, Ostrava Mesto, Czechia

Herlev Hospital ( Site 0251); 🇩🇰 Herlev, Hovedstaden, Denmark

Institut de cancérologie Strasbourg Europe (ICANS) ( Site 0350); 🇫🇷 Strasbourg, Bas-Rhin, France

HYKS. ( Site 0302); 🇫🇮 Helsinki, Uusimaa, Finland

Universitaetsklinikum Carl Gustav Carus Dresden ( Site 0403); 🇩🇪 Dresden, Sachsen, Germany

Universitaetsklinikum Duesseldorf ( Site 0410); 🇩🇪 Duesseldorf, Nordrhein-Westfalen, Germany

Policlinico S. Orsola-Malpighi ( Site 0606); 🇮🇹 Bologna, Italy

Medical Oncology Ospedale San Donato ( Site 0609); 🇮🇹 Arezzo, Italy

Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Trento-Oncology Unit ( Site 0605; 🇮🇹 Verona, Veneto, Italy

Istituto Oncologico Veneto IRCCS ( Site 0603); 🇮🇹 Padova, Veneto, Italy

Azienda Ospedaliera Policlinico di Bari ( Site 0610); 🇮🇹 Bari, Italy

Fondazione Policlinico Universitario A. Gemelli ( Site 0607); 🇮🇹 Roma, Italy

Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 0604); 🇮🇹 Modena, Italy

Istituto Nazionale dei Tumori ( Site 0601); 🇮🇹 Milano, Italy

Fujita Health University ( Site 1016); 🇯🇵 Toyoake, Aichi, Japan

National Cancer Center Hospital East ( Site 1001); 🇯🇵 Kashiwa, Chiba, Japan

Ehime University Hospital ( Site 1014); 🇯🇵 Toon, Ehime, Japan

Yokohama City University Hospital ( Site 1015); 🇯🇵 Yokohama, Kanagawa, Japan

Kanagawa cancer center ( Site 1021); 🇯🇵 Yokohama, Kanagawa, Japan

Nara Medical University Hospital ( Site 1009); 🇯🇵 Kashihara, Nara, Japan

The Cancer Institute Hospital of JFCR ( Site 1000); 🇯🇵 Tokyo, Japan

Okayama University Hospital ( Site 1020); 🇯🇵 Okayama, Japan

Nippon Medical School Hospital ( Site 1010); 🇯🇵 Tokyo, Japan

National Cancer Center Hospital ( Site 1003); 🇯🇵 Tokyo, Japan

National Cancer Center ( Site 1204); 🇰🇷 Gyeonggi-do, Kyonggi-do, Korea, Republic of

Korea University Anam Hospital ( Site 1203); 🇰🇷 Seoul, Korea, Republic of

Hadassah Medical-Oncology department ( Site 1164); 🇷🇺 Moscow, Moskovskaya Oblast, Russian Federation

Omsk Clinical Oncology Dispensary ( Site 1150); 🇷🇺 Omsk, Omskaya Oblast, Russian Federation

N.N. Blokhin NMRCO ( Site 1156); 🇷🇺 Moscow, Moskva, Russian Federation

Central Clinical Hospital with Polyclinic ( Site 1157); 🇷🇺 Moscow, Moskva, Russian Federation

SBHI SPb Clinical Research Centre of specialized types of medical care ( Site 1159); 🇷🇺 Saint-Petersburg, Sankt-Peterburg, Russian Federation

Hospital Universitari Vall d Hebron ( Site 1250); 🇪🇸 Barcelona, Cataluna, Spain

Instituto Valenciano de Oncologia - IVO ( Site 1254); 🇪🇸 Valencia, Valenciana, Comunitat, Spain

Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 1305); 🇹🇷 Istanbul, Turkey

Izmir Katip Celebi Universitesi Ataturk Egitim ve Arastirma Hastanesi ( Site 1306); 🇹🇷 Izmir, Turkey

Western General Hospital ( Site 1400); 🇬🇧 Edinburgh, Edinburgh, City Of, United Kingdom

Barts Health NHS Trust ( Site 1407); 🇬🇧 London, London, City Of, United Kingdom

Medway Maritime Hospital ( Site 1406); 🇬🇧 Gillingham, United Kingdom

University of Alabama - Birmingham ( Site 1538); 🇺🇸 Birmingham, Alabama, United States

University Of Colorado ( Site 1540); 🇺🇸 Aurora, Colorado, United States

Ochsner Medical Center ( Site 1522); 🇺🇸 New Orleans, Louisiana, United States

Henry Ford Cancer Center ( Site 1511); 🇺🇸 Detroit, Michigan, United States

University of North Carolina at Chapel Hill ( Site 1537); 🇺🇸 Chapel Hill, North Carolina, United States

Oregon Health & Science University ( Site 1553); 🇺🇸 Portland, Oregon, United States

Medical University of South Carolina ( Site 1518); 🇺🇸 Charleston, South Carolina, United States

Queen Mary Hospital ( Site 1051); 🇭🇰 Hong Kong, Hong Kong

Princess Margaret Hospital. ( Site 1053); 🇭🇰 Lai Chi Kok, Hong Kong

Prince of Wales Hospital ( Site 1050); 🇭🇰 Hong Kong, Hong Kong

Queen Elizabeth Hospital. ( Site 1052); 🇭🇰 Kowloon, Hong Kong