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

April 30, 2026 updated by: Merck Sharp & Dohme LLC

An Open-label, Randomized Phase 3 Study of MK-6482 Versus Everolimus in Participants With Advanced Renal Cell Carcinoma That Has Progressed After Prior PD-1/L1 and VEGF-Targeted Therapies

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

755

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • Minas Gerais
      • Belo Horizonte, Minas Gerais, Brazil, 30130-090
        • Centro Avançado de Tratamento Oncológico- CENANTRON ( Site 1657)
    • Paraná
      • Curitiba, Paraná, Brazil, 80510-130
        • Instituto de Cancer e Transplante de Curitiba ICTR ( Site 1650)
    • Rio Grande do Norte
      • Natal, Rio Grande do Norte, Brazil, 59062-000
        • Liga Norte Riograndense Contra o Cancer ( Site 1651)
    • Rio Grande do Sul
      • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
        • Hospital de Clinicas de Porto Alegre ( Site 1655)
    • São Paulo
      • São Paulo, São Paulo, Brazil, 01323-001
        • BP - A Beneficencia Portuguesa de São Paulo ( Site 1653)
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • BC Cancer - Vancouver Center ( Site 0155)
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 1V7
        • Nova Scotia Health Authority QEII-HSC ( Site 0150)
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • Juravinski Cancer Centre ( Site 0154)
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Research Institute ( Site 0153)
    • Quebec
      • Montreal, Quebec, Canada, H2X 3E4
        • Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0151)
      • Québec, Quebec, Canada, G1J 1Z4
        • Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0152)
  • Chile
    • Araucania
      • Temuco, Araucania, Chile, 4800827
        • Centro Investigación del Cáncer James Lind ( Site 0004)
    • Region M. de Santiago
      • Santiago, Region M. de Santiago, Chile, 8420383
        • Bradfordhill ( Site 0003)
  • Colombia
    • Antioquia
      • Medellín, Antioquia, Colombia, 050021
        • Fundacion Centro de Investigacion Clinica CIC ( Site 1703)
    • Bogota D.C.
      • Bogotá, Bogota D.C., Colombia, 110221
        • Administradora Country SA - Clinica del Country ( Site 1701)
      • Bogotá, Bogota D.C., Colombia, 111321
        • Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 1702)
    • Cesar Department
      • Valledupar, Cesar Department, Colombia, 200001
        • Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 1709)
    • Risaralda Department
      • Pereira, Risaralda Department, Colombia, 660006
        • Oncologos del Occidente S.A. ( Site 1708)
  • Czechia
      • Hradec Králové, Czechia, 50005
        • Fakultni nemocnice Hradec Kralove ( Site 0106)
      • Olomouc, Czechia, 77900
        • Fakultni nemocnice Olomouc ( Site 0104)
      • Prague, Czechia, 100 34
        • Fakultni nemocnice Kralovske Vinohrady ( Site 0102)
      • Prague, Czechia, 140 59
        • Fakultni Thomayerova nemocnice ( Site 0107)
    • Brno-mesto
      • Brno, Brno-mesto, Czechia, 656 53
        • Masarykuv onkologicky ustav ( Site 0105)
    • Ostrava Mesto
      • Ostrava, Ostrava Mesto, Czechia, 708 52
        • Fakultni nemocnice Ostrava ( Site 0103)
  • Denmark
    • Capital Region
      • Herlev, Capital Region, Denmark, 2730
        • Herlev Hospital ( Site 0251)
    • Central Jutland
      • Aarhus, Central Jutland, Denmark, 8200
        • Aarhus University Hospital Skejby ( Site 0250)
  • Finland
    • Northern Savonia
      • Kuopio, Northern Savonia, Finland, 70210
        • Kuopion Yliopistollinen Sairaala ( Site 0304)
    • Pirkanmaa
      • Tampere, Pirkanmaa, Finland, 33520
        • Tampereen yliopistollinen sairaala ( Site 0300)
    • Southwest Finland
      • Turku, Southwest Finland, Finland, 20520
        • TYKS T-sairaala Syopatautien pkl ( Site 0301)
    • Uusimaa
      • Helsinki, Uusimaa, Finland, 00290
        • HYKS. ( Site 0302)
  • France
    • Alsace
      • Strasbourg, Alsace, France, 67200
        • Institut de cancérologie Strasbourg Europe (ICANS) ( Site 0350)
    • Aquitaine
      • Bordeaux, Aquitaine, France, 33075
        • CHU de Bordeaux Hop St ANDRE ( Site 0359)
    • Calvados
      • Caen, Calvados, France, 14075
        • Centre Francois Baclesse ( Site 0360)
    • Doubs
      • Besançon, Doubs, France, 25000
        • CHU Besancon - Hopital Jean Minjoz ( Site 0351)
    • Gard
      • Nîmes, Gard, France, 30029
        • Institut de Cancerologie du Gard - CHU Caremeau ( Site 0352)
    • Lorraine
      • Vandœuvre-lès-Nancy, Lorraine, France, 54519
        • Institut de Cancérologie de Lorraine Alexis Vautrin ( Site 0356)
    • Rhone
      • Pierre-Bénite, Rhone, France, 69310
        • Centre Hospitalier Lyon Sud ( Site 0354)
    • Val-de-Marne
      • Villejuif, Val-de-Marne, France, 94800
        • Gustave Roussy ( Site 0353)
  • Germany
      • Berlin, Germany, 10117
        • Universitaetsmedizin Berlin ( Site 0400)
      • Hamburg, Germany, 20246
        • Universitatsklinikum Hamburg ( Site 0408)
    • Baden-Wurttemberg
      • Tübingen, Baden-Wurttemberg, Germany, 72076
        • Universitaetsklinik fuer Urologie ( Site 0405)
    • North Rhine-Westphalia
      • Düsseldorf, North Rhine-Westphalia, Germany, 40225
        • Universitaetsklinikum Duesseldorf ( Site 0410)
      • Essen, North Rhine-Westphalia, Germany, 45122
        • Universitaetsklinikum Essen ( Site 0401)
    • Saxony
      • Dresden, Saxony, Germany, 01307
        • Universitaetsklinikum Carl Gustav Carus Dresden ( Site 0403)
    • Saxony-Anhalt
      • Magdeburg, Saxony-Anhalt, Germany, 39120
        • Universitaetsklinikum Magdeburg A.o.R. ( Site 0404)
    • Thuringia
      • Jena, Thuringia, Germany, 07747
        • Universitaetsklinikum Jena ( Site 0402)
  • Hong Kong
      • Hong Kong, Hong Kong
        • Prince of Wales Hospital ( Site 1050)
      • Hong Kong, Hong Kong, 000000
        • Queen Mary Hospital ( Site 1051)
      • Kowloon, Hong Kong
        • Queen Elizabeth Hospital. ( Site 1052)
      • Lai Chi Kok, Hong Kong
        • Princess Margaret Hospital. ( Site 1053)
  • Hungary
      • Budapest, Hungary, 1085
        • Semmelweis Egyetem ( Site 0501)
      • Budapest, Hungary, 1122
        • Orszagos Onkologiai Intezet ( Site 0503)
      • Zalaegerszeg, Hungary, 8900
        • Zala Megyei Szent Rafael Korhaz ( Site 0509)
    • Bekes County
      • Gyula, Bekes County, Hungary, H-5700
        • Bekes Megyei Kozponti Korhaz - Pandy Kalman Tagkorhaza ( Site 0505)
    • Borsod-Abauj Zemplen county
      • Miskolc, Borsod-Abauj Zemplen county, Hungary, 3526
        • Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Okta-Klinikai Onkológiai és Sugárterápiás Ce ( Site 0502)
    • Hajdú-Bihar
      • Debrecen, Hajdú-Bihar, Hungary, 4032
        • Debreceni Egyetem Klinikai Kozpont ( Site 0504)
  • Italy
      • Arezzo, Italy, 52100
        • Medical Oncology Ospedale San Donato ( Site 0609)
      • Bari, Italy, 70124
        • Azienda Ospedaliera Policlinico di Bari ( Site 0610)
      • Bologna, Italy, 40138
        • AOU di Bologna Policlinico S Orsola Malpighi ( Site 0606)
      • Milan, Italy, 20133
        • Istituto Nazionale dei Tumori ( Site 0601)
      • Modena, Italy, 41125
        • Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 0604)
      • Padova, Italy, 35128
        • Istituto Oncologico Veneto IRCCS ( Site 0603)
      • Pavia, Italy, 27100
        • Fondazione Salvatore Maugeri clinica del lavoro ( Site 0600)
      • Roma, Italy, 00168
        • Fondazione Policlinico Universitario A. Gemelli ( Site 0607)
      • Terni, Italy, 05100
        • Azienda Ospedaliera Santa Maria ( Site 0602)
    • Veneto
      • Verona, Veneto, Italy, 37126
        • Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Trento-Oncology Unit ( Site 0605)
  • Japan
      • Fukuoka, Japan, 812-8582
        • Kyushu University Hospital ( Site 1007)
      • Hiroshima, Japan, 734-8551
        • Hiroshima University Hospital ( Site 1019)
      • Niigata, Japan, 951-8520
        • Niigata University Medical & Dental Hospital ( Site 1022)
      • Okayama, Japan, 700-8558
        • Okayama University Hospital ( Site 1020)
      • Tokushima, Japan, 770-8503
        • Tokushima University Hospital ( Site 1017)
      • Tokyo, Japan, 104-0045
        • National Cancer Center Hospital ( Site 1003)
      • Tokyo, Japan, 105-8470
        • Toranomon Hospital ( Site 1004)
      • Tokyo, Japan, 160-8582
        • Keio University Hospital ( Site 1002)
      • Tokyo, Japan, 135-8550
        • Cancer Institute Hospital of JFCR ( Site 1000)
    • Aichi-ken
      • Toyoake, Aichi-ken, Japan, 470-1192
        • Fujita Health University Hospital ( Site 1016)
    • Chiba
      • Kashiwa, Chiba, Japan, 2778577
        • National Cancer Center Hospital East ( Site 1001)
    • Ehime
      • Tōon, Ehime, Japan, 791-0295
        • Ehime University Hospital ( Site 1014)
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 060-8543
        • Sapporo Medical University Hospital ( Site 1008)
    • Kanagawa
      • Yokohama, Kanagawa, Japan, 236-0004
        • Yokohama City University Hospital ( Site 1015)
      • Yokohama, Kanagawa, Japan, 241-8515
        • Kanagawa Cancer Center ( Site 1021)
    • Nara
      • Kashihara, Nara, Japan, 634-0813
        • Nara Medical University Hospital ( Site 1009)
    • Osaka
      • Sayama, Osaka, Japan, 589-8511
        • Kindai University Hospital ( Site 1011)
      • Suita, Osaka, Japan, 565-0871
        • The University of Osaka Hospital ( Site 1006)
    • Saitama
      • Hidaka, Saitama, Japan, 350-1298
        • Saitama Medical University International Medical Center ( Site 1012)
    • Shizuoka
      • Hamamatsu, Shizuoka, Japan, 431-3192
        • Hamamatsu University Hospital ( Site 1005)
    • Tokyo
      • Bunkyo-ku, Tokyo, Japan, 113-8603
        • Nippon Medical School Hospital ( Site 1010)
    • Toyama
      • Toyoma, Toyama, Japan, 930-0194
        • Toyama University Hospital ( Site 1013)
    • Yamaguchi
      • Ube, Yamaguchi, Japan, 755-8505
        • Yamaguchi University Hospital ( Site 1018)
  • Norway
    • Akershus
      • Lorenskog, Akershus, Norway, 1478
        • Akershus universitetssykehus ( Site 0851)
    • Hordaland
      • Bergen, Hordaland, Norway, 5021
        • Helse Bergen HF - Haukeland Universitetssykehus ( Site 0854)
  • Russia
    • Krasnoyarsk Krai
      • Krasnoyarsk, Krasnoyarsk Krai, Russia, 660133
        • Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 1151)
    • Moscow
      • Moscow, Moscow, Russia, 105077
        • SBIH City clinical hospital named after D.D. Pletniov ( Site 1160)
      • Moscow, Moscow, Russia, 115478
        • N.N. Blokhin NMRCO ( Site 1156)
      • Moscow, Moscow, Russia, 117997
        • Russian Scientific Center of Roentgenoradiology ( Site 1155)
      • Moscow, Moscow, Russia, 119146
        • First Moscow State Medical University n.a. I.M.Sechenov ( Site 1163)
      • Moscow, Moscow, Russia, 121359
        • Central Clinical Hospital with Polyclinic ( Site 1157)
    • Moscow Oblast
      • Moscow, Moscow Oblast, Russia, 121205
        • Hadassah Medical-Oncology department ( Site 1164)
    • Omsk Oblast
      • Omsk, Omsk Oblast, Russia, 644013
        • Omsk Clinical Oncology Dispensary ( Site 1150)
    • Sankt-Peterburg
      • Saint Petersburg, Sankt-Peterburg, Russia, 197758
        • Russian Scientific Center of Radiology and Surgical Technologies ( Site 1153)
      • Saint Petersburg, Sankt-Peterburg, Russia, 197758
        • SBHI SPb Clinical Research Centre of specialized types of medical care ( Site 1159)
      • Saint Petersburg, Sankt-Peterburg, Russia, 198255
        • City clinical oncological dispensary ( Site 1154)
  • South Korea
      • Seoul, South Korea, 02841
        • Korea University Anam Hospital ( Site 1203)
      • Seoul, South Korea, 03722
        • Severance Hospital Yonsei University Health System ( Site 1202)
      • Seoul, South Korea, 05505
        • Asan Medical Center ( Site 1200)
      • Seoul, South Korea, 06351
        • Samsung Medical Center ( Site 1201)
    • Kyonggi-do
      • Gyeonggi-do, Kyonggi-do, South Korea, 10408
        • National Cancer Center ( Site 1204)
    • Taejon-Kwangyokshi
      • Daejeon, Taejon-Kwangyokshi, South Korea, 35015
        • Chungnam National University Hospital ( Site 1205)
  • Spain
      • Madrid, Spain, 28034
        • Hospital Ramon y Cajal ( Site 1253)
      • Madrid, Spain, 28041
        • Hospital General Universitario 12 de Octubre ( Site 1252)
    • Catalonia
      • Barcelona, Catalonia, Spain, 08035
        • Hospital Universitari Vall d Hebron ( Site 1250)
      • Barcelona, Catalonia, Spain, 08908
        • Instituto Catalan de Oncologia - ICO ( Site 1251)
    • Valenciana, Comunitat
      • Valencia, Valenciana, Comunitat, Spain, 46009
        • Instituto Valenciano de Oncologia - IVO ( Site 1254)
  • Sweden
    • Jönköping County
      • Jönköping, Jönköping County, Sweden, 551 85
        • Laenssjukhuset Ryhov ( Site 1853)
    • Skåne County
      • Malmö, Skåne County, Sweden, 214 28
        • Malmo Universitetssjukhus ( Site 1851)
    • Stockholm County
      • Stockholm, Stockholm County, Sweden, 171 76
        • Karolinska Universitetssjukhuset Solna ( Site 1850)
    • Västerbotten County
      • Umeå, Västerbotten County, Sweden, 901 85
        • Norrlands Universitetssjukhus ( Site 1856)
  • Taiwan
      • Kaohsiung City, Taiwan, 83301
        • Chang Gung Medical Foundation - Kaohsiung ( Site 1104)
      • Taichung, Taiwan, 407
        • Taichung Veterans General Hospital ( Site 1105)
      • Tainan, Taiwan, 704
        • National Cheng Kung University Hospital ( Site 1103)
      • Taipei, Taiwan, 10002
        • National Taiwan University Hospital ( Site 1100)
      • Taipei, Taiwan, 11217
        • Taipei Veterans General Hospital ( Site 1101)
      • Taoyuan, Taiwan, 333
        • Chang Gung Medical Foundation-Linkou Branch-Urology ( Site 1106)
  • Turkey (Türkiye)
      • Ankara, Turkey (Türkiye), 06100
        • Ankara Universitesi Tip Fakultesi ( Site 1311)
      • Ankara, Turkey (Türkiye), 06230
        • Hacettepe Universitesi Tip Fakultesi ( Site 1300)
      • Ankara, Turkey (Türkiye), 06560
        • Gazi Universitesi Tip Fakultesi ( Site 1308)
      • Edirne, Turkey (Türkiye), 22030
        • Trakya University Medical Faculty Balkan Oncology Hospital ( Site 1302)
      • Istanbul, Turkey (Türkiye), 34098
        • Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 1305)
      • Istanbul, Turkey (Türkiye), 34722
        • Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 1303)
      • Izmir, Turkey (Türkiye), 35100
        • Ege Universitesi Tip Fakultesi Hastanesi ( Site 1304)
      • Izmir, Turkey (Türkiye), 35360
        • Izmir Katip Celebi Universitesi Ataturk Egitim ve Arastirma Hastanesi ( Site 1306)
  • Ukraine
      • Kyiv, Ukraine, 03115
        • Kyiv City Clinical Oncology Center ( Site 1450)
    • Dnipropetrovsk Oblast
      • Dnipropetrovsk, Dnipropetrovsk Oblast, Ukraine, 49005
        • ME І.І. Mechnykov Dnipro Regional Clinical Hospital ( Site 1453)
    • Ivano-Frankivsk Oblast
      • Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine, 76018
        • MI Precarpathian Clinical Oncology Center ( Site 1452)
  • United Kingdom
      • Gillingham, United Kingdom, ME7 5NY
        • Medway Maritime Hospital ( Site 1406)
      • Manchester, United Kingdom, M20 4BX
        • The Christie NHS Foundation Trust ( Site 1401)
    • Cambridgeshire
      • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
        • Cambridge University Hospitals NHSFT ( Site 1405)
    • Edinburgh, City of
      • Edinburgh, Edinburgh, City of, United Kingdom, EH4 2XU
        • Western General Hospital ( Site 1400)
    • Glasgow City
      • Glasgow, Glasgow City, United Kingdom, G12 0YN
        • The Beatson West of Scotland Cancer Centre ( Site 1402)
    • London, City of
      • London, London, City of, United Kingdom, EC1A 7BE
        • Barts Health NHS Trust ( Site 1407)
      • London, London, City of, United Kingdom, SW3 6JJ
        • Royal Marsden NHS Foundation Trust ( Site 1403)
      • London, London, City of, United Kingdom, W6 8RF
        • Imperial Healthcare NHS Trust Charing Cross Hospital ( Site 1409)
      • Sutton, London, City of, United Kingdom, SM2 5PT
        • Royal Marsden Hospital Sutton-Surrey ( Site 1411)
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Faculty Office Towers 1132 ( Site 1538)
    • California
      • La Jolla, California, United States, 92093-0698
        • University of California San Diego Moores Cancer Center ( Site 1546)
      • Santa Rosa, California, United States, 95403
        • St. Joseph Heritage Healthcare Local Lab ( Site 1531)
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Cancer Center ( Site 1540)
      • Highlands Ranch, Colorado, United States, 80129
        • UCHealth Highlands Ranch Hospital ( Site 1560)
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20016
        • Sibley Memorial Hospital ( Site 1559)
    • Georgia
      • Marietta, Georgia, United States, 30060
        • Northwest Georgia Oncology Centers PC ( Site 1520)
    • Illinois
      • Chicago, Illinois, United States, 60637
        • The University of Chicago Medical Center ( Site 1539)
    • Louisiana
      • New Orleans, Louisiana, United States, 70121-2429
        • Ochsner Medical Center ( Site 1522)
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 1514)
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital ( Site 1558)
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center ( Site 1501)
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute ( Site 1505)
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Cancer Center ( Site 1511)
    • Mississippi
      • Hattiesburg, Mississippi, United States, 39401
        • Hattiesburg Clinic ( Site 1509)
    • Montana
      • Billings, Montana, United States, 59102
        • St. Vincent Frontier Cancer Center ( Site 1549)
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • John Theurer Cancer Center at Hackensack University Medical Center ( Site 1513)
    • New York
      • Rochester, New York, United States, 14642
        • University of Rochester Medical Center ( Site 1543)
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • University of North Carolina at Chapel Hill ( Site 1537)
    • Ohio
      • Cincinnati, Ohio, United States, 45242
        • Oncology Hematology Care, Inc. ( Site 1524)
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Main ( Site 1504)
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74146
        • Oklahoma Cancer Specialists and Research Institute, LLC ( Site 1523)
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University ( Site 1553)
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Abramson Cancer Center ( Site 1525)
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center ( Site 1506)
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina ( Site 1518)
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Henry Joyce Cancer Clinic ( Site 1544)
    • Texas
      • Austin, Texas, United States, 78731
        • Texas Oncology-Austin Central ( Site 1533)
      • Dallas, Texas, United States, 75230
        • Texas Oncology, P.A.-Dallas ( Site 1534)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Belzutifan
Randomized participants received 120 mg of belzutifan orally once daily (QD), until disease progression or discontinuation.
Drug: Belzutifan
Oral tablets
Other Names:
  • MK-6482
  • WELIREG™
Active Comparator: Everolimus
Randomized participants received 10 mg of Everolimus orally QD, until disease progression or discontinuation.
Drug: Everolimus
Oral tablets
Other Names:
  • Afinitor
  • Zortress
  • Afinitor DISPERZ
Experimental: Safety Run-In
Non-Randomized participants enrolled into the Safety Run-in received up to 120 mg of belzutifan QD.
Drug: Belzutifan
Oral tablets
Other Names:
  • MK-6482
  • WELIREG™

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
Time Frame: 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.
Up to approximately 39 months
Overall Survival (OS)
Time Frame: 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.
Up to approximately 49 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR
Time Frame: 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.
Up to approximately 31 months
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
Time Frame: 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.
Up to approximately 49 months
Number of Participants Who Experience One or More Adverse Events (AEs)
Time Frame: 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.
Up to approximately 78 months
Number of Participants Who Discontinue Study Treatment Due to an AE
Time Frame: 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.
Up to approximately 78 months
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
Time Frame: 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.
Up to approximately 39 months
TTD in Physical Functioning Using the EORTC QLQ-C30 Items 1- 5 Score
Time Frame: 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.
Up to approximately 39 months
TTD in Disease Symptoms Using the Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease-related Symptoms (FKSI-DRS) Items 1-9 Score
Time Frame: 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.
Up to approximately 39 months
Change From Baseline to Week 17 in the HRQoL Using the EORTC QLQ-C30 Items 29 and 30 Combined Score
Time Frame: 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.
Baseline (Day 1) and week 17
Change From Baseline to Week 17 in Physical Functioning Using the EORTC QLQ-C30 Items 1- 5 Score
Time Frame: 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.
Baseline (Day 1) and week 17
Change From Baseline to Week 17 in Disease Symptoms Using the FKSI-DRS Items 1-9 Score
Time Frame: 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.
Baseline (Day 1) and week 17
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
Time Frame: 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.
Baseline (Day 1) and week 17

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Investigators

  • Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 27, 2020

Primary Completion (Actual)

April 15, 2024

Study Completion (Estimated)

September 17, 2026

Study Registration Dates

First Submitted

December 10, 2019

First Submitted That Met QC Criteria

December 10, 2019

First Posted (Actual)

December 12, 2019

Study Record Updates

Last Update Posted (Actual)

May 14, 2026

Last Update Submitted That Met QC Criteria

April 30, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 6482-005
  • MK-6482 (Other Identifier: MSD)
  • 205262 (Registry Identifier: Japic-CTI)
  • 2019-003444-72 (EudraCT Number)
  • jRCT2080225166 (Other Identifier: jRCT)
  • U1111-1294-1321 (Registry Identifier: UTN)
  • 2023-506635-15-00 (Registry Identifier: EU CT)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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