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

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: Carcinoma, Renal Cell
• Intervention / Treatment: Drug: Belzutifan; Drug: Everolimus

• Study Type: Interventional
• Enrollment (Estimated): 736
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 01321-030
    • Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 1653)
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30130-090
      • Centro Avancado de Tratamento Oncologico ( Site 1657)
  • Parana
    • Curitiba, Parana, Brazil, 80510-130
      • Instituto de Cancer e Transplante de Curitiba ICTR ( Site 1650)
  • Rio Grande Do Norte
    • Natal, Rio Grande Do Norte, Brazil, 59075-740
      • 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)
• Canada
  • Quebec, Canada, G1R 2J6
    • CHUQ-Univ Laval-Hotel Dieu de Quebec ( Site 0152)
  • 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)
• Chile
  • Araucania
    • Temuco, Araucania, Chile, Temuco
      • Centro Investigación del Cáncer James Lind ( Site 0004)
  • Region M. De Santiago
    • Santiago, Region M. De Santiago, Chile, 8420383
      • Bradfordhill ( Site 0003)
• Colombia
  • Antioquia
    • Medellin, Antioquia, Colombia, 050021
      • Fundacion Centro de Investigacion Clinica CIC ( Site 1703)
  • Cesar
    • Valledupar, Cesar, Colombia, 200001
      • Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 1709)
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia, 111321
      • Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 1702)
  • Distrito Capital De Bogota
    • Bogota, Distrito Capital De Bogota, Colombia, 110221
      • Administradora Country SA - Clinica del Country ( Site 1701)
  • Risaralda
    • Pereira, Risaralda, Colombia, 660001
      • Oncologos del Occidente S.A. ( Site 1708)
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove ( Site 0106)
  • Olomouc, Czechia, 779 00
    • Fakultni nemocnice Olomouc ( Site 0104)
  • Praha 10, Czechia, 100 34
    • Fakultni nemocnice Kralovske Vinohrady ( Site 0102)
  • Praha 4, 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
  • Hovedstaden
    • Herlev, Hovedstaden, Denmark, 2730
      • Herlev Hospital ( Site 0251)
  • Midtjylland
    • Aarhus, Midtjylland, Denmark, 8200
      • Aarhus University Hospital Skejby ( Site 0250)
• Finland
  • Pirkanmaa
    • Tampere, Pirkanmaa, Finland, 33520
      • Tampereen yliopistollinen sairaala ( Site 0300)
  • Pohjois-Savo
    • Kuopio, Pohjois-Savo, Finland, 70210
      • Kuopion Yliopistollinen Sairaala ( Site 0304)
  • Uusimaa
    • Helsinki, Uusimaa, Finland, 00290
      • HYKS. ( Site 0302)
  • Varsinais-Suomi
    • Turku, Varsinais-Suomi, Finland, 20521
      • TYKS T-sairaala Syopatautien pkl ( Site 0301)
• France
  • Aquitaine
    • Bordeaux, Aquitaine, France, 33075
      • CHU de Bordeaux Hop St ANDRE ( Site 0359)
  • Bas-Rhin
    • Strasbourg, Bas-Rhin, France, 67200
      • Institut de cancérologie Strasbourg Europe (ICANS) ( Site 0350)
  • Calvados
    • Caen, Calvados, France, 14076
      • Centre Francois Baclesse ( Site 0360)
  • Doubs
    • Besancon, Doubs, France, 25000
      • CHU Besancon - Hopital Jean Minjoz ( Site 0351)
  • Gard
    • Nimes, Gard, France, 30029
      • Institut de Cancerologie du Gard - CHU Caremeau ( Site 0352)
  • Meurthe-et-Moselle
    • Vandoeuvre les Nancy, Meurthe-et-Moselle, France, 54519
      • Centre Alexis Vautrin Institut de Cancerologie de Lorraine ( Site 0356)
  • Rhone
    • Pierre Benite, 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-Eppendorf ( Site 0408)
  • Baden-Wurttemberg
    • Tuebingen, Baden-Wurttemberg, Germany, 72076
      • Universitaetsklinik fuer Urologie ( Site 0405)
  • Nordrhein-Westfalen
    • Duesseldorf, Nordrhein-Westfalen, Germany, 40225
      • Universitaetsklinikum Duesseldorf ( Site 0410)
    • Essen, Nordrhein-Westfalen, Germany, 45122
      • Universitaetsklinikum Essen ( Site 0401)
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • Universitaetsklinikum Carl Gustav Carus Dresden ( Site 0403)
  • Sachsen-Anhalt
    • Magdeburg, Sachsen-Anhalt, Germany, 39120
      • Universitaetsklinikum Magdeburg A.o.R. ( Site 0404)
  • Thuringen
    • Jena, Thuringen, Germany, 07747
      • Universitaetsklinikum Jena ( Site 0402)
• Hong Kong
  • Hong Kong, Hong Kong
    • Prince of Wales Hospital ( Site 1050)
  • Hong Kong, Hong Kong
    • 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)
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont ( Site 0504)
  • Zalaegerszeg, Hungary, 8900
    • Zala Megyei Szent Rafael Korhaz ( Site 0509)
  • Bekes
    • Gyula, Bekes, Hungary, H-5700
      • Bekes Megyei Kozponti Korhaz - Pandy Kalman Tagkorhaza ( Site 0505)
  • Borsod-Abauj-Zemplen
    • Miskolc, Borsod-Abauj-Zemplen, Hungary, 3526
      • Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Okta-Klinikai Onkológiai és Sugárterápiás Ce
• Italy
  • Arezzo, Italy, 52100
    • Medical Oncology Ospedale San Donato ( Site 0609)
  • Bari, Italy, 70124
    • Azienda Ospedaliera Policlinico di Bari ( Site 0610)
  • Bologna, Italy, 40138
    • Policlinico S. Orsola-Malpighi ( Site 0606)
  • Milano, Italy, 20133
    • Istituto Nazionale dei Tumori ( Site 0601)
  • Modena, Italy, 41125
    • Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 0604)
  • 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
    • Padova, Veneto, Italy, 35128
      • Istituto Oncologico Veneto IRCCS ( Site 0603)
    • 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-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-Department of Urology ( Site 1017)
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital ( Site 1003)
  • Tokyo, Japan, 105-8470
    • Toranomon Hospital ( Site 1004)
  • Tokyo, Japan, 113-8603
    • Nippon Medical School Hospital ( Site 1010)
  • Tokyo, Japan, 135-8550
    • The Cancer Institute Hospital of JFCR ( Site 1000)
  • Tokyo, Japan, 160-8582
    • Keio University Hospital ( Site 1002)
  • Aichi
    • Toyoake, Aichi, Japan, 470-1192
      • Fujita Health University ( Site 1016)
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East ( Site 1001)
  • Ehime
    • Toon, 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
    • Osakasayama, Osaka, Japan, 589-8511
      • Kindai University Hospital- Osakasayama Campus-Urology ( Site 1011)
    • Suita, Osaka, Japan, 565-0871
      • Osaka University Hospital ( Site 1006)
  • Saitama
    • Hidaka-city, Saitama, Japan, 350-1298
      • Saitama Medical University International Medical Center ( Site 1012)
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 431-3192
      • Hamamatsu University Hospital ( Site 1005)
  • Toyama
    • Toyoma, Toyama, Japan, 930-0194
      • Toyama University Hospital ( Site 1013)
  • Yamaguchi
    • Ube, Yamaguchi, Japan, 755-8505
      • Yamaguchi University Hospital ( Site 1018)
• Korea, Republic of
  • Seoul, Korea, Republic of, 02841
    • Korea University Anam Hospital ( Site 1203)
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital Yonsei University Health System ( Site 1202)
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center ( Site 1200)
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center ( Site 1201)
  • Kyonggi-do
    • Gyeonggi-do, Kyonggi-do, Korea, Republic of, 10408
      • National Cancer Center ( Site 1204)
  • Taejon-Kwangyokshi
    • Daejeon, Taejon-Kwangyokshi, Korea, Republic of, 35015
      • Chungnam National University Hospital ( Site 1205)
• Norway
  • Akershus
    • Lorenskog, Akershus, Norway, 1478
      • Akershus universitetssykehus ( Site 0851)
  • Hordaland
    • Bergen, Hordaland, Norway, 5021
      • Helse Bergen HF - Haukeland Universitetssykehus ( Site 0854)
• Russian Federation
  • Krasnoyarskiy Kray
    • Krasnoyarsk, Krasnoyarskiy Kray, Russian Federation, 660133
      • Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 1151)
  • Moskovskaya Oblast
    • Moscow, Moskovskaya Oblast, Russian Federation, 121205
      • Hadassah Medical-Oncology department ( Site 1164)
  • Moskva
    • Moscow, Moskva, Russian Federation, 105077
      • SBIH City clinical hospital named after D.D. Pletniov ( Site 1160)
    • Moscow, Moskva, Russian Federation, 115478
      • N.N. Blokhin NMRCO ( Site 1156)
    • Moscow, Moskva, Russian Federation, 117997
      • Russian Scientific Center of Roentgenoradiology ( Site 1155)
    • Moscow, Moskva, Russian Federation, 119146
      • First Moscow State Medical University n.a. I.M.Sechenov ( Site 1163)
    • Moscow, Moskva, Russian Federation, 121359
      • Central Clinical Hospital with Polyclinic ( Site 1157)
  • Omskaya Oblast
    • Omsk, Omskaya Oblast, Russian Federation, 644013
      • Omsk Clinical Oncology Dispensary ( Site 1150)
  • Sankt-Peterburg
    • Saint-Petersburg, Sankt-Peterburg, Russian Federation, 197758
      • SBHI SPb Clinical Research Centre of specialized types of medical care ( Site 1159)
    • Sankt-Petersburg, Sankt-Peterburg, Russian Federation, 198255
      • City clinical oncological dispensary ( Site 1154)
    • St. Petersburg, Sankt-Peterburg, Russian Federation, 197758
      • Russian Scientific Center of Radiology and Surgical Technologies ( Site 1153)
• Spain
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal ( Site 1253)
  • Barcelona
    • L Hospitalet De Llobregat, Barcelona, Spain, 08908
      • Instituto Catalan de Oncologia - ICO ( Site 1251)
  • Cataluna
    • Barcelona, Cataluna, Spain, 08035
      • Hospital Universitari Vall d Hebron ( Site 1250)
  • Madrid, Comunidad De
    • Madrid, Madrid, Comunidad De, Spain, 28041
      • Hospital General Universitario 12 de Octubre ( Site 1252)
  • Valenciana, Comunitat
    • Valencia, Valenciana, Comunitat, Spain, 46009
      • Instituto Valenciano de Oncologia - IVO ( Site 1254)
• Sweden
  • Jonkopings Lan
    • Jönköping, Jonkopings Lan, Sweden, 551 85
      • Laenssjukhuset Ryhov ( Site 1853)
  • Skane Lan
    • Malmo, Skane Lan, Sweden, 214 28
      • Malmo Universitetssjukhus ( Site 1851)
  • Stockholms Lan
    • Stockholm, Stockholms Lan, Sweden, 171 76
      • Karolinska Universitetssjukhuset Solna ( Site 1850)
  • Vasterbottens Lan
    • Umeå, Vasterbottens Lan, Sweden, 901 85
      • Norrlands Universitetssjukhus ( Site 1856)
• Taiwan
  • Kaohsiung, Taiwan, 83301
    • Chang Gung Medical Foundation - Kaohsiung ( Site 1104)
  • Taichung, Taiwan, 40705
    • 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
  • Ankara, Turkey, 06100
    • Ankara Universitesi Tip Fakultesi ( Site 1311)
  • Ankara, Turkey, 06230
    • Hacettepe Universitesi Tip Fakultesi ( Site 1300)
  • Ankara, Turkey, 06560
    • Gazi Universitesi Tip Fakultesi ( Site 1308)
  • Edirne, Turkey, 22030
    • Trakya University Medical Faculty Balkan Oncology Hospital ( Site 1302)
  • Istanbul, Turkey, 34098
    • Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 1305)
  • Istanbul, Turkey, 34722
    • Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 1303)
  • Izmir, Turkey, 35100
    • Ege Universitesi Tip Fakultesi Hastanesi ( Site 1304)
  • Izmir, Turkey, 35360
    • Izmir Katip Celebi Universitesi Ataturk Egitim ve Arastirma Hastanesi ( Site 1306)
• Ukraine
  • Dnipropetrovska Oblast
    • Dnipropetrovsk, Dnipropetrovska Oblast, Ukraine, 49005
      • MI Dnipr Regional Clinical Hospital named after I.I. Mechnikov ( Site 1453)
  • Ivano-Frankivska Oblast
    • Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine, 76018
      • MI Precarpathian Clinical Oncology Center ( Site 1452)
  • Kyivska Oblast
    • Kyiv, Kyivska Oblast, Ukraine, 03115
      • Kyiv City Clinical Oncology Center ( Site 1450)
• 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)
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Royal Marsden Hospital Sutton-Surrey ( Site 1411)
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama - Birmingham ( 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 ( Site 1531)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University Of Colorado ( Site 1540)
    • Highlands Ranch, Colorado, United States, 80129
      • UCHealth Highlands Ranch Hospital ( Site 1560)
  • District of Columbia
    • Washington, 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
      • Ochsner Medical Center ( Site 1522)
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • 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, 14620
      • 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 ( Site 1504)
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74146
      • Oklahoma Cancer Specialists and Research Institute, LLC ( Site 1523)
  • Oregon
    • Portland, Oregon, United States, 97232
      • 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

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

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Belzutifan; Participants receive 120 mg of belzutifan orally once daily (QD)	Drug: Belzutifan; Oral tablets; Other Names: MK-6482; WELIREG™
Active Comparator: Everolimus; Participants receive 10 mg of Everolimus orally once daily (QD)	Drug: Everolimus; Oral tablets; Other Names: Afinitor; Zortress; Afinitor DISPERZ

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)	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 will be presented	Up to approximately 39 months
Overall Survival (OS)	Time from randomization to death due to any cause	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	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 will be presented.	Up to approximately 39 months
Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR	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 will be presented.	Up to approximately 39 months
Number of Participants Who Experience One or More Adverse Events (AEs)	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 49 months
Number of Participants Who Discontinue Study Treatment Due to an AE	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 49 months
Time to 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 Score	TTD is defined as the time from baseline to the first onset of a ≥10-point negative change (decrease) from baseline in global health status (Item 29) & quality of life (Item 30) combined score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in global health status and quality of life combined score, will be presented. A longer TTD indicates a better outcome.	Up to approximately 49 months
TTD in Physical Functioning Using the EORTC QLQ-C30 Items 1- 5 Score	TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in physical functioning (EORTC QLQ-C30 Items 1-5) score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from Baseline in physical functioning score, will be presented.	Up to approximately 49 months
TTD in Disease Symptoms Using the Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease-related Symptoms (FKSI-DRS) Items 1-9 Score	The FKSI-DRS index consists of a 9-item questionnaire that assesses the extent of participant symptoms from kidney cancer over the previous 7 days. Responses are scored on a 5-point scale (0=Not at all to 4=Very much) and summed to generate an index symptom score. These scores can range from 0 to 36, with a higher score indicating more favorable kidney cancer symptom status.	Up to approximately 49 months
Change From Baseline in HRQoL Using the EORTC QLQ-C30 Items 29 and 30 Score	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses for global health status (Item 29) & quality of life (Item 30) are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 scores will be presented.	Baseline (Day 1) and up to approximately 49 months
Change From Baseline in Physical Functioning Using the EORTC QLQ-C30 Items 1- 5 Score	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life 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). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better quality of life. The change from baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) score will be presented.	Baseline (Day 1) and up to approximately 49 months
Change From Baseline in Disease Symptoms Using the FKSI-DRS Items 1-9 Score	The FKSI-DRS index consists of a 9-item questionnaire that assesses the extent of participant symptoms from kidney cancer over the previous 7 days. Responses are scored on a 5-point scale (0=Not at all to 4=Very much) and summed to generate an index symptom score. These scores can range from 0 to 36, with a higher score indicating more favorable kidney cancer symptom status.	Baseline (Day 1) and up to approximately 49 months
Change from Baseline in European Quality of Life 5 Dimensions, 5-level Questionnaire (EuroQoL EQ-5D-5L) Health Utility Score	The EQ-5D-5L questionnaire assesses 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/ depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty, which are coded on a scale from 1 (no problems) to 5 (extreme problems). The participant is also asked to indicate his/her current health state by selecting the most appropriate level on a visual analog scale from 0 to 100, with 0 being the worst imaginable health state.	Baseline (Day 1) and up to approximately 49 months

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2020
• Primary Completion (Estimated): September 17, 2025
• Study Completion (Estimated): September 17, 2025

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): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Hypoxia inducible factor 1B (HIF-1B); Hypoxia inducible factor 2 alpha (HIF-2 alpha); Hypoxia inducible factor 2α (HIF-2α); Renal Cell Carcinoma (RCC); Kidney Cancer; MK6482; PT-2977; PT2977; Hypoxia inducible Factor (HIF)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protein Kinase Inhibitors; MTOR Inhibitors; Everolimus; Belzutifan
• Other Study ID Numbers: 6482-005; MK-6482 (Other Identifier: Merck); 205262 (Registry Identifier: Japic-CTI); 2019-003444-72 (EudraCT Number); jRCT2080225166 (Other Identifier: jRCT); 2023-506635-15 (Other Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/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