A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)

May 4, 2026 updated by: Merck Sharp & Dohme LLC

An Open-label, Randomized, Phase 3 Study of MK-6482 in Combination With Lenvatinib (MK-7902) vs Cabozantinib in Participants With Advanced Renal Cell Carcinoma Who Have Progressed After Prior Anti-PD-1/L1 Therapy

This study will compare the efficacy and safety of belzutifan + lenvatinib versus cabozantinib in participants with advanced renal cell carcinoma (RCC) with clear cell component after prior therapy.

The primary hypothesis is that belzutifan + lenvatinib is superior to cabozantinib in terms of progression-free survival or overall survival.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

747

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

  • Argentina
    • Buenos Aires
      • CABA, Buenos Aires, Argentina, C1120AAT
        • Centro de Urología (CDU) ( Site 0803)
      • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1426ANZ
        • Instituto Alexander Fleming ( Site 0800)
      • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1280AEB
        • Hospital Británico de Buenos Aires-Oncology ( Site 0801)
    • Buenos Aires F.D.
      • Buenos Aires, Buenos Aires F.D., Argentina, C1419AHN
        • Asociación de Beneficencia Hospital Sirio Libanés ( Site 0804)
    • Santa Fe Province
      • Rosario, Santa Fe Province, Argentina, 2000
        • Sanatorio Británico-Clinical Oncology Department ( Site 0802)
      • Rosario, Santa Fe Province, Argentina, S2000DSV
        • Sanatorio Parque ( Site 0806)
  • Australia
    • New South Wales
      • St Leonards, New South Wales, Australia, 2065
        • GenesisCare North Shore ( Site 4011)
    • South Australia
      • Elizabeth Vale, South Australia, Australia, 5112
        • Lyell McEwin Hospital ( Site 4004)
    • Victoria
      • Frankston, Victoria, Australia, 3199
        • Peninsula Health Frankston Hospital ( Site 4001)
      • Melbourne, Victoria, Australia, 3000
        • Peter MacCallum Cancer Centre-Parkville Cancer Clinical Trials Unit (PCCTU) ( Site 4010)
  • Austria
      • Vienna, Austria, 1020
        • Krankenhaus der Barmherzigen Brüder Wien ( Site 1041)
      • Vienna, Austria, 1090
        • Medizinische Universität Wien ( Site 1021)
    • State of Vienna
      • Vienna, State of Vienna, Austria, 1160
        • Klinik Ottakring-1.Medizinische Abteilung - Zentrum für Onkologie und Hämatologie ( Site 1031)
    • Styria
      • Graz, Styria, Austria, 8036
        • Medizinische Universitätsklinik Graz ( Site 1051)
    • Upper Austria
      • Linz, Upper Austria, Austria, 4020
        • Ordensklinikum Linz GmbH Elisabethinen-Urologie ( Site 1001)
  • Belgium
      • Liège, Belgium, 4000
        • CHU de Liege ( Site 1102)
    • Bruxelles-Capitale, Region de
      • Anderlecht, Bruxelles-Capitale, Region de, Belgium, 1070
        • Institut Jules Bordet ( Site 1103)
      • Brussels, Bruxelles-Capitale, Region de, Belgium, 1200
        • Cliniques Universitaires Saint Luc - Bruxelles ( Site 1105)
    • Hainaut
      • Gilly, Hainaut, Belgium, 6060
        • Grand Hopital de Charleroi ( Site 1104)
    • Oost-Vlaanderen
      • Ghent, Oost-Vlaanderen, Belgium, 9000
        • UZ Gent ( Site 1100)
    • Vlaams-Brabant
      • Leuven, Vlaams-Brabant, Belgium, 3000
        • UZ Leuven ( Site 1101)
  • Brazil
      • São Paulo, Brazil, 01321-001
        • BP - A Beneficencia Portuguesa de São Paulo-Medical Oncology ( Site 0311)
      • São Paulo, Brazil, 01321-001
        • Hospital Paulistano - Amil Clinical Research ( Site 0308)
    • Rio Grande do Norte
      • Natal, Rio Grande do Norte, Brazil, 59151600
        • Liga Norte Riograndense Contra o Cancer ( Site 0313)
    • Rio Grande do Sul
      • Porto Alegre, Rio Grande do Sul, Brazil, 90110-270
        • Centro Gaucho Integrado de Oncologia ( Site 0304)
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 5G2
        • Arthur J.E. Child Comprehensive Cancer Centre ( Site 0109)
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute ( Site 0111)
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • BC Cancer Vancouver-Clinical Trials Unit ( Site 0110)
    • New Brunswick
      • Moncton, New Brunswick, Canada, E1C 6Z8
        • The Moncton Hospital ( Site 0101)
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0114)
      • Kingston, Ontario, Canada, K7L 2V7
        • Kingston Health Sciences Centre ( Site 0105)
      • Ottawa, Ontario, Canada, K1H 8L6
        • The Ottawa Hospital - General Campus-The Ottawa Hospital Cancer Centre ( Site 0116)
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Health Sciences - Odette Cancer Centre ( Site 0113)
    • Quebec
      • Greenfield Park, Quebec, Canada, J4V 2H1
        • CISSS de la Monteregie-Centre ( Site 0103)
      • Québec, Quebec, Canada, G1J 1Z4
        • Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0115)
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0102)
  • Chile
    • Araucania
      • Temuco, Araucania, Chile, 4800827
        • James Lind Centro de Investigacion del Cancer ( Site 0402)
    • Region M. de Santiago
      • Santiago, Region M. de Santiago, Chile, 8420383
        • Bradfordhill-Clinical Area ( Site 0400)
  • Colombia
    • Antioquia
      • Medellín, Antioquia, Colombia, 050030
        • Fundacion Colombiana de Cancerología Clinica Vida ( Site 0505)
    • Cesar Department
      • Valledupar, Cesar Department, Colombia, 200001
        • Sociedad De Oncologia Y Hematologia Del Cesar-Oncology ( Site 0508)
    • Cundinamarca
      • Bogotá, Cundinamarca, Colombia, 111511
        • Instituto Nacional de Cancerología-Clinical Oncology ( Site 0500)
    • Santander Department
      • Piedecuesta, Santander Department, Colombia, 681017
        • Fundación Cardiovascular de Colombia ( Site 0501)
  • Czechia
      • Hradec Králové, Czechia, 500 05
        • Fakultni nemocnice Hradec Kralove-Klinika onkologie a radioterapie ( Site 2201)
    • Brno-mesto
      • Brno, Brno-mesto, Czechia, 656 53
        • Masarykuv onkologicky ustav-Klinika komplexni onkologicke pece ( Site 2203)
    • Praha 4
      • Prague, Praha 4, Czechia, 140 59
        • Fakultni Thomayerova nemocnice-Onkologicka klinika 1. LF UK ( Site 2200)
    • Praha 5
      • Prague, Praha 5, Czechia, 150 06
        • Fakultni nemocnice v Motole-Onkologicka klinika 2. LF UK a FN Motol ( Site 2205)
    • South Bohemian Region
      • České Budějovice, South Bohemian Region, Czechia, 37001
        • Nemocnice Ceske Budejovice-Onkologicke oddeleni ( Site 2204)
  • Finland
    • Pirkanmaa
      • Tampere, Pirkanmaa, Finland, 33520
        • Tampereen yliopistollinen sairaala ( Site 1801)
    • Southwest Finland
      • Turku, Southwest Finland, Finland, 20520
        • TYKS ( Site 1802)
    • Uusimaa
      • Helsinki, Uusimaa, Finland, 00290
        • HYKS ( Site 1800)
  • France
      • Paris, France, 75020
        • Hopital Tenon ( Site 1213)
    • Ain
      • Reims, Ain, France, 51726
        • Institut Jean Godinot ( Site 1216)
    • Alpes-Maritimes
      • Nice, Alpes-Maritimes, France, 06189
        • Centre Antoine Lacassagne ( Site 1217)
    • Bas-Rhin
      • Strasbourg, Bas-Rhin, France, 67200
        • Hopitaux Universitaires de Strasbourg- Hopital de Hautepierre ( Site 1218)
    • Gironde
      • Bordeaux, Gironde, France, 33000
        • CHU de Bordeaux- Hopital Saint Andre ( Site 1209)
    • Haute-Garonne
      • Toulouse, Haute-Garonne, France, 31059
        • Institut Claudius Regaud ( Site 1215)
    • Haute-Vienne
      • Limoges, Haute-Vienne, France, 87039
        • Clinique Francois Chenieux ( Site 1210)
    • Loire-Atlantique
      • Saint-Herblain, Loire-Atlantique, France, 44805
        • Institut de Cancerologie de l Ouest Centre Rene Gauducheau ( Site 1201)
    • Maine-et-Loire
      • Angers, Maine-et-Loire, France, 49055
        • Institut de Cancerologie de l Ouest Site Paul Papin ( Site 1200)
  • Germany
      • Berlin, Germany, 10117
        • Charite Universitaetsmedizin Berlin ( Site 1321)
      • Berlin, Germany, 13125
        • HELIOS Klinikum Berlin-Buch ( Site 1311)
    • Baden-Wurttemberg
      • Freiburg im Breisgau, Baden-Wurttemberg, Germany, 79106
        • Klinik fuer Urologie ( Site 1303)
      • Heidelberg, Baden-Wurttemberg, Germany, 69120
        • NCT-Department of Medical Oncology ( Site 1320)
    • Bavaria
      • Nuremberg, Bavaria, Germany, 90419
        • Klinikum Nuernberg Nord ( Site 1300)
    • Hesse
      • Frankfurt am Main, Hesse, Germany, 60590
        • Universitaetsklinikum Frankfurt ( Site 1301)
    • North Rhine-Westphalia
      • Aachen, North Rhine-Westphalia, Germany, 52074
        • Universitaetsklinikum Aachen AOER ( Site 1317)
    • Saarland
      • Homburg/ Saar, Saarland, Germany, 66421
        • Universitaetsklinikum des Saarlandes ( Site 1305)
    • Saxony-Anhalt
      • Halle, Saxony-Anhalt, Germany, 06120
        • Krankenhaus Martha Maria Halle-Doelau ( Site 1314)
    • Thuringia
      • Erfurt, Thuringia, Germany, 99089
        • Helios Klinikum Erfurt GmbH ( Site 1315)
  • Greece
      • Thessaloniki, Greece, 570 01
        • European Interbalkan Medical Center-Oncology Department ( Site 3300)
    • Achaia
      • Pátrai, Achaia, Greece, 26504
        • UNIVERSITY HOSPITAL OF PATRAS-DIVISION OF ONCOLOGY ( Site 3302)
    • Attica
      • Athens, Attica, Greece, 115 28
        • Alexandra General Hospital of Athens-ONCOLOGY DEPT. ( Site 3304)
      • Athens, Attica, Greece, 151 25
        • Athens Medical Center ( Site 3303)
      • Chaïdári, Attica, Greece, 124 62
        • ATTIKON GENERAL UNIVERSITY HOSPITAL ( Site 3301)
  • Ireland
      • Dublin, Ireland, D24NR0A
        • Tallaght University Hospital ( Site 3200)
      • Dublin, Ireland, D07 R2WY
        • Mater Misericordiae University Hospital ( Site 3201)
      • Dublin, Ireland, D07 R2WY
        • Mater Private Hospital - Dublin ( Site 3202)
  • Italy
      • Arezzo, Italy, 52100
        • Medical Oncology Ospedale San Donato ( Site 1404)
      • Bari, Italy, 70124
        • Azienda Ospedaliera Policlinico di Bari ( Site 1402)
      • Milan, Italy, 20132
        • IRCCS Ospedale San Raffaele ( Site 1409)
      • Milan, Italy, 20133
        • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 1400)
      • Pavia, Italy, 27100
        • Istituti Clinici Scientifici Maugeri Spa ( Site 1403)
      • Roma, Italy, 00168
        • Fondazione Policlinico Universitario Agostino Gemelli-Medical Oncology ( Site 1410)
      • Terni, Italy, 05100
        • Azienda Ospedaliera S. Maria di Terni ( Site 1401)
      • Verona, Italy, 37126
        • Ospedale Maggiore Borgo Trento ( Site 1408)
    • Forli-Cesena
      • Meldola, Forli-Cesena, Italy, 47014
        • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori ( Site 1407)
    • Milano
      • Rozzano, Milano, Italy, 20089
        • Istituto Clinico Humanitas Research Hospital ( Site 1406)
    • Torino
      • Orbassano, Torino, Italy, 10043
        • Ospedale San Luigi Gonzaga ( Site 1405)
  • Japan
      • Fukuoka, Japan, 812-8582
        • Kyushu University Hospital ( Site 5005)
      • Niigata, Japan, 951-8520
        • Niigata University Medical & Dental Hospital ( Site 5013)
      • Osaka, Japan, 541-8567
        • Osaka Prefectural Hospital Organization Osaka International Cancer Institute ( Site 5016)
      • Tokyo, Japan, 113-8603
        • Nippon Medical School Hospital ( Site 5006)
      • Tokyo, Japan, 123-8558
        • Tokyo Women's Medical University Adachi Medical Center ( Site 5015)
      • Tokyo, Japan, 160-8582
        • Keio University Hospital ( Site 5011)
    • Aichi-ken
      • Toyoake, Aichi-ken, Japan, 470-1192
        • Fujita Health University Hospital ( Site 5003)
    • Chiba
      • Kashiwa, Chiba, Japan, 2778577
        • National Cancer Center Hospital East ( Site 5000)
      • Sakura, Chiba, Japan, 285-8741
        • Toho University Sakura Medical Center ( Site 5014)
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 060-8543
        • Sapporo Medical University Hospital ( Site 5008)
    • Hyōgo
      • Kobe, Hyōgo, Japan, 650-0047
        • Kobe City Medical Center General Hospital ( Site 5017)
    • Kanagawa
      • Yokohama, Kanagawa, Japan, 236-0004
        • Yokohama City University Hospital ( Site 5007)
    • Nara
      • Kashihara, Nara, Japan, 634-0813
        • Nara Medical University Hospital ( Site 5002)
    • Osaka
      • Sakai, Osaka, Japan, 590-0197
        • Kindai University Hospital ( Site 5010)
      • Suita, Osaka, Japan, 565-0871
        • The University of Osaka Hospital ( Site 5012)
    • Shizuoka
      • Hamamatsu, Shizuoka, Japan, 431-3192
        • Hamamatsu University Hospital ( Site 5004)
    • Tokyo
      • Bunkyo-ku, Tokyo, Japan, 113-8510
        • Institute of Science Tokyo Hospital ( Site 5009)
      • Minato-ku, Tokyo, Japan, 105-8470
        • Toranomon Hospital ( Site 5001)
  • Netherlands
      • Utrecht, Netherlands, 3584 CX
        • Universitair Medisch Centrum Utrecht ( Site 1910)
    • Limburg
      • Sittard-Geleen, Limburg, Netherlands, 6162 BG
        • Zuyderland Medical Centre-Trialbureau Interne Geneeskunde ( Site 1904)
    • North Brabant
      • Breda, North Brabant, Netherlands, 4818 CK
        • Amphia Hospital Location Molengracht ( Site 1912)
    • North Holland
      • Amsterdam, North Holland, Netherlands, 1066 CX
        • Antoni van Leeuwenhoek Ziekenhuis ( Site 1901)
    • Provincie Friesland
      • Leeuwarden, Provincie Friesland, Netherlands, 8934 AD
        • Medisch Centrum Leeuwarden ( Site 1905)
    • South Holland
      • Rotterdam, South Holland, Netherlands, 3015 GD
        • Erasmus MC ( Site 1913)
      • Schiedam, South Holland, Netherlands, 3118 JH
        • Franciscus Gasthuis & Vlietland, Locatie Vlietland ( Site 1909)
      • The Hague, South Holland, Netherlands, 2545 AA
        • Haga Ziekenhuis locatie Leyweg-Oncology ( Site 1917)
  • Poland
    • Greater Poland Voivodeship
      • Poznan, Greater Poland Voivodeship, Poland, 60-569
        • Uniwersytecki Szpital Kliniczny w Poznaniu ( Site 2401)
    • Kuyavian-Pomeranian Voivodeship
      • Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland, 85-796
        • Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 2402)
    • Lesser Poland Voivodeship
      • Krakow, Lesser Poland Voivodeship, Poland, 31-115
        • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - O-Klinika Onkologii Klinicznej ( Site 2403)
    • Masovian Voivodeship
      • Warsaw, Masovian Voivodeship, Poland, 02-781
        • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 2400)
  • Romania
    • Cluj
      • Cluj-Napoca, Cluj, Romania, 400015
        • Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 2500)
      • Cluj-Napoca, Cluj, Romania, 400015
        • Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 2501)
    • Dolj
      • Craiova, Dolj, Romania, 200542
        • Centrul de Oncologie "Sfântul Nectarie" ( Site 2502)
  • Russia
    • Ivanovo Oblast
      • Ivanovo, Ivanovo Oblast, Russia, 153040
        • Ivanovo Regional Oncology Dispensary ( Site 2616)
    • Moscow
      • Moscow, Moscow, Russia, 119285
        • FSBI United Hospital with Polyclinic ( Site 2613)
      • Moscow, Moscow, Russia, 125130
        • SHI of Moscow City Oncology Clinical Hospital - 62 ( Site 2614)
    • Moscow Oblast
      • Krasnogorsk, Moscow Oblast, Russia, 143442
        • MEDSI Clinical Hospital on Pyatnitsky Highway-Departmentof Antitumor Drug therapy ( Site 2618)
      • Moscow, Moscow Oblast, Russia, 121205
        • Hadassah Medical-Oncology department ( Site 2609)
    • Volgograd Oblast
      • Volzhsky, Volgograd Oblast, Russia, 404120
        • Volgograd Regional Uronephrological Center ( Site 2615)
    • Yaroslavl Oblast
      • Yaroslavl, Yaroslavl Oblast, Russia, 150054
        • Yaroslavl Regional Cancer Hospital-Oncology ( Site 2619)
  • South Korea
      • Seoul, South Korea, 05505
        • Asan Medical Center ( Site 4200)
      • Seoul, South Korea, 06351
        • Samsung Medical Center ( Site 4201)
    • Jeonranamdo
      • Hwasun, Jeonranamdo, South Korea, 58128
        • Chonnam National University Hwasun Hospital-Oncology ( Site 4203)
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 1507)
      • Barcelona, Spain, 08036
        • Hospital Clinic i Provincial ( Site 1500)
      • Barcelona, Spain, 08041
        • Hospital Santa Creu i Sant Pau ( Site 1501)
      • Madrid, Spain, 28009
        • Hospital General Universitario Gregorio Maranon ( Site 1505)
      • Madrid, Spain, 28040
        • Hospital Clinico San Carlos... ( Site 1504)
      • Seville, Spain, 41013
        • Hospital Virgen del Rocio ( Site 1503)
    • La Coruna
      • A Coruña, La Coruna, Spain, 15006
        • Complejo Hospitalario Universitario A Coruna ( Site 1502)
    • Madrid, Comunidad de
      • Madrid, Madrid, Comunidad de, Spain, 28041
        • Hospital Universitario 12 de Octubre-Medical Oncology ( Site 1508)
  • Switzerland
    • Canton Ticino
      • Bellinzona, Canton Ticino, Switzerland, 6500
        • Istituto Oncologica della Svizzera Italiana (IOSI) ( Site 1604)
    • Canton of Geneva
      • Geneva, Canton of Geneva, Switzerland, 1211
        • Hopitaux Universitaires de Geneve HUG ( Site 1602)
    • Canton of Zurich
      • Zurich, Canton of Zurich, Switzerland, 8001
        • Universitaetsspital Zuerich ( Site 1601)
    • Kanton Graubünden
      • Chur, Kanton Graubünden, Switzerland, 7000
        • Kantonsspital Graubuenden ( Site 1600)
  • United Kingdom
    • Aberdeen City
      • Aberdeen, Aberdeen City, United Kingdom, AB25 2ZN
        • Aberdeen Royal Infirmary-Department of Oncology ( Site 3105)
    • Bath And North East Somerset
      • Bath, Bath And North East Somerset, United Kingdom, BA1 3NG
        • Royal United Hospital Bath England ( Site 3108)
    • England
      • Nottingham, England, United Kingdom, NG5 1PF
        • Nottingham University Hospitals NHS Trust. City Hospital Campus ( Site 3106)
    • Essex
      • Southend, Essex, United Kingdom, SS0 0RY
        • Southend University Hospital ( Site 3112)
    • London, City of
      • London, London, City of, United Kingdom, W6 8RF
        • Imperial Healthcare NHS Trust Charing Cross Hospital ( Site 3107)
      • Northwood, London, City of, United Kingdom, HA6 2RN
        • Mount Vernon Cancer Centre ( Site 3101)
    • Somerset
      • Taunton, Somerset, United Kingdom, TA1 5DA
        • Musgrove Park Hospital ( Site 3103)
    • Wales
      • Swansea, Wales, United Kingdom, SA2 8QA
        • Singleton Hospital ( Site 3111)
  • United States
    • Arizona
      • Chandler, Arizona, United States, 85224
        • Ironwood Cancer & Research Centers ( Site 0077)
    • California
      • Los Angeles, California, United States, 90048
        • Cedars Sinai Medical Center ( Site 0027)
      • Los Angeles, California, United States, 90404
        • UCLA Hematology/Oncology - Santa Monica ( Site 0048)
      • Orange, California, United States, 92868
        • St. Joseph Hospital-The Center for Cancer Prevention and Treatment ( Site 0095)
      • Orange, California, United States, 92868
        • University of California, Irvine ( Site 0029)
      • Santa Monica, California, United States, 90404
        • Providence Saint John's Health Center ( Site 0083)
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Georgetown University Medical Center ( Site 0006)
    • Florida
      • Orlando, Florida, United States, 32806
        • Orlando Health, Inc. ( Site 0035)
      • Orlando, Florida, United States, 32804
        • AdventHealth Orlando-AdventHealth Medical Group Hematology & Oncology at Orlandoc ( Site 0003)
    • Georgia
      • Athens, Georgia, United States, 30607
        • University Cancer & Blood Center, LLC ( Site 0057)
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital ( Site 0012)
    • Illinois
      • Chicago, Illinois, United States, 60607
        • Rush University Medical Center ( Site 0040)
      • Peoria, Illinois, United States, 61615
        • Illinois Cancer Care, PC ( Site 0008)
    • Indiana
      • Fort Wayne, Indiana, United States, 46845
        • Parkview Cancer Institute ( Site 0088)
    • Kentucky
      • Louisville, Kentucky, United States, 40207
        • Norton Cancer Institute - St. Matthews ( Site 0065)
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane University School of Medicine ( Site 0098)
    • Massachusetts
      • Burlington, Massachusetts, United States, 01805
        • Lahey Hospital & Medical Center ( Site 0090)
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
        • Cancer & Hematology Centers of Western Michigan ( Site 0018)
    • Minnesota
      • Saint Louis Park, Minnesota, United States, 55426
        • HealthPartners Cancer Research Center-HealthPartners Frauenshuh Cancer Center ( Site 0005)
    • Mississippi
      • Jackson, Mississippi, United States, 39213
        • University of Mississippi Medical Ctr ( Site 0037)
    • Nebraska
      • Lincoln, Nebraska, United States, 68516
        • Cancer Partners of Nebraska ( Site 0086)
    • New Jersey
      • New Brunswick, New Jersey, United States, 08903
        • Rutgers Cancer Institute of New Jersey ( Site 0078)
    • New York
      • Lake Success, New York, United States, 11042
        • R.J. Zuckerberg Cancer Center-Medical Oncology ( Site 0013)
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center ( Site 0055)
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Levine Cancer Institute ( Site 0004)
      • Durham, North Carolina, United States, 27710
        • Duke Cancer Institute ( Site 0096)
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103
        • Lehigh Valley Hospital- Cedar Crest-Oncology Clinical Trials ( Site 0056)
    • Texas
      • Dallas, Texas, United States, 75235
        • University of Texas, Southwestern Medical Center ( Site 0015)
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute-HCI Clinical Trials Office ( Site 7001)
    • Vermont
      • Burlington, Vermont, United States, 05401
        • University of Vermont Medical Center ( Site 0001)
    • Virginia
      • Roanoke, Virginia, United States, 24014
        • Blue Ridge Cancer Care - Roanoke ( Site 0043)
    • Washington
      • Seattle, Washington, United States, 98109
        • Seattle Cancer Care Alliance-Renal/Melanoma/MCC ( Site 0093)
      • Wenatchee, Washington, United States, 98801
        • Central Washington Health Services Association d/b/a Confluence Health ( Site 0061)

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:

  • Unresectable, locally advanced or metastatic clear cell renal cell carcinoma (RCC).
  • Disease progression on or after an anti-programmed cell death-1/ligand 1 (PD-1/L1) therapy as either first or second-line treatment for locally advanced/metastatic RCC or as adjuvant treatment or neoadjuvant/adjuvant with progression on or within 6 months of last dose.
  • Measurable disease per RECIST 1.1 criteria as assessed by local study investigator.
  • Karnofsky performance status (KPS) score of at least 70% assessed within 10 days before randomization.
  • Received no more than 2 prior systemic regimens including: one anti-PD-1/L1 containing adjuvant or neoadjuvant/adjuvant regimens with progression on or within 6 months from the last dose of that regimen OR one or 2 regimens for locoregional/advanced disease
  • Received only 1 prior antiPD-1/L1 therapy for adjuvant, neoadjuvant/adjuvant or locally advanced/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 belzutifan or lenvatinib in the belzutifan+lenvatinib arm, whichever occurs last, and 23 days after the last dose of cabozantinib.
  • A female participant is eligible to participate if they are 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 in the belzutifan+ lenvatinib arm, or 120 days after the last dose of study intervention in the cabozantinib arm.
  • Adequately controlled blood pressure.
  • Adequate organ function.

Exclusion Criteria:

  • A pulse oximeter reading <92% at rest, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen.
  • Known additional malignancy that is progressing or has required active treatment within the past 3 years except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy.
  • Known central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Clinically significant cardiac disease within 6 months of first dose of study intervention.
  • Prolongation of QTc interval to >480 ms.
  • Symptomatic pleural effusion (e.g.,cough, dyspnea, pleuritic chest pain) that is not clinically stable.
  • Pre-existing ≥Grade 3 gastrointestinal or nongastrointestinal fistula.
  • Moderate to severe hepatic impairment.
  • History of significant bleeding within 3 months before randomization.
  • History of solid organ transplantation.
  • Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.
  • Unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption).
  • Known hypersensitivity or allergy to the active pharmaceutical ingredients or any component of the study intervention formulations.
  • Received colony-stimulating factors [eg, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GMCSF) or recombinant erythropoietin (EPO)] within 28 days before randomization.
  • Prior treatment with belzutifan or another hypoxia-inducible factor (HIF)-2α inhibitor.
  • Prior treatment with lenvatinib.
  • Prior treatment with cabozantinib.
  • Currently participating in a study of an investigational agent or using an investigational device.
  • Active infection requiring systemic therapy.
  • History of human immunodeficiency virus (HIV) infection.
  • History of hepatitis B or known active hepatitis C 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 + Lenvatinib
Belzutifan 120 mg and lenvatinib 20 mg orally once a day
Drug: Belzutifan
Immediate-release 40 mg tablet
Other Names:
  • MK-6482
  • PT2977
  • WELIREG™
Drug: Lenvatinib
Capsule available in 4 mg and 10 mg dosages
Other Names:
  • E7080
  • Lenvima
  • MK-7902
Active Comparator: Cabozantinib
Cabozantinib 60 mg orally once a day
Drug: Cabozantinib
Tablet available in 20 mg, 40 mg and 60 mg dosages
Other Names:
  • BMS-907351
  • Cabometyx
  • Cometriq
  • XL184

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
Time Frame: Up to approximately 34 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 will be presented.
Up to approximately 34 months
Overall Survival (OS)
Time Frame: Up to approximately 44 months
OS is defined as time from randomization to death due to any cause.
Up to approximately 44 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
Time Frame: Up to approximately 24 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 will be presented.
Up to approximately 24 months
Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
Time Frame: Up to approximately 44 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 will be presented.
Up to approximately 44 months
Number of Participants Who Experienced One or More Adverse Events (AEs)
Time Frame: Up to approximately 44 months
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Up to approximately 44 months
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
Time Frame: Up to approximately 44 months
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Up to approximately 44 months

Collaborators and Investigators

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

Sponsor

Merck Sharp & Dohme LLC

Collaborators

Eisai Inc.

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 25, 2021

Primary Completion (Actual)

February 2, 2026

Study Completion (Estimated)

February 11, 2027

Study Registration Dates

First Submitted

October 9, 2020

First Submitted That Met QC Criteria

October 9, 2020

First Posted (Actual)

October 14, 2020

Study Record Updates

Last Update Posted (Actual)

May 5, 2026

Last Update Submitted That Met QC Criteria

May 4, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 6482-011
  • MK-6482-011 (Other Identifier: MSD)
  • jRCT2031210311 (Other Identifier: jRCT(Japan Registry of Clinical Trials))
  • 2020-002075-35 (EudraCT Number)
  • U1111-1302-2815 (Registry Identifier: UTN)
  • 2024-510620-39-00 (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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