AzTrials
AzTrials

Carcinoma, Renal CellPhase 3NCT04195750

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

A Phase 3 study testing Belzutifan and Everolimus in people with Carcinoma, Renal Cell, run by Merck Sharp & Dohme LLC at 172 sites in 23 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Renal Cell
What is being tested?
Belzutifan and Everolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
755 participants
Where
172 sitesin 23 countries
Study dates
27 Feb 2020to 14 Oct 2026
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

172 sites in 23 countries.

172 sites in 23 countries

United States29 sites

  • University of Colorado Cancer Center ( Site 1540)

    Aurora, Colorado, 80045

  • Texas Oncology-Austin Central ( Site 1533)

    Austin, Texas, 78731

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 1514)

    Baltimore, Maryland, 21287

  • St. Vincent Frontier Cancer Center ( Site 1549)

    Billings, Montana, 59102

  • Faculty Office Towers 1132 ( Site 1538)

    Birmingham, Alabama, 35294

  • Massachusetts General Hospital ( Site 1558)

    Boston, Massachusetts, 02114

  • Beth Israel Deaconess Medical Center ( Site 1501)

    Boston, Massachusetts, 02215

  • Dana Farber Cancer Institute ( Site 1505)

    Boston, Massachusetts, 02215

  • University of North Carolina at Chapel Hill ( Site 1537)

    Chapel Hill, North Carolina, 27514

  • Medical University of South Carolina ( Site 1518)

    Charleston, South Carolina, 29425

  • The University of Chicago Medical Center ( Site 1539)

    Chicago, Illinois, 60637

  • Oncology Hematology Care, Inc. ( Site 1524)

    Cincinnati, Ohio, 45242

  • Cleveland Clinic Main ( Site 1504)

    Cleveland, Ohio, 44195

  • Texas Oncology, P.A.-Dallas ( Site 1534)

    Dallas, Texas, 75230

  • Henry Ford Cancer Center ( Site 1511)

    Detroit, Michigan, 48202

  • John Theurer Cancer Center at Hackensack University Medical Center ( Site 1513)

    Hackensack, New Jersey, 07601

  • Hattiesburg Clinic ( Site 1509)

    Hattiesburg, Mississippi, 39401

  • UCHealth Highlands Ranch Hospital ( Site 1560)

    Highlands Ranch, Colorado, 80129

  • University of California San Diego Moores Cancer Center ( Site 1546)

    La Jolla, California, 92093-0698

  • Northwest Georgia Oncology Centers PC ( Site 1520)

    Marietta, Georgia, 30060

  • Henry Joyce Cancer Clinic ( Site 1544)

    Nashville, Tennessee, 37232

  • Ochsner Medical Center ( Site 1522)

    New Orleans, Louisiana, 70121-2429

  • Abramson Cancer Center ( Site 1525)

    Philadelphia, Pennsylvania, 19104

  • Fox Chase Cancer Center ( Site 1506)

    Philadelphia, Pennsylvania, 19111

  • Oregon Health & Science University ( Site 1553)

    Portland, Oregon, 97239

  • University of Rochester Medical Center ( Site 1543)

    Rochester, New York, 14642

  • St. Joseph Heritage Healthcare Local Lab ( Site 1531)

    Santa Rosa, California, 95403

  • Oklahoma Cancer Specialists and Research Institute, LLC ( Site 1523)

    Tulsa, Oklahoma, 74146

  • Sibley Memorial Hospital ( Site 1559)

    Washington D.C., District of Columbia, 20016

Other trials in United States

Japan23 sites

  • Nippon Medical School Hospital ( Site 1010)

    Bunkyo-ku, Tokyo, 113-8603

  • Kyushu University Hospital ( Site 1007)

    Fukuoka, 812-8582

  • Hamamatsu University Hospital ( Site 1005)

    Hamamatsu, Shizuoka, 431-3192

  • Saitama Medical University International Medical Center ( Site 1012)

    Hidaka, Saitama, 350-1298

  • Hiroshima University Hospital ( Site 1019)

    Hiroshima, 734-8551

  • Nara Medical University Hospital ( Site 1009)

    Kashihara, Nara, 634-0813

  • National Cancer Center Hospital East ( Site 1001)

    Kashiwa, Chiba, 2778577

  • Niigata University Medical & Dental Hospital ( Site 1022)

    Niigata, 951-8520

  • Okayama University Hospital ( Site 1020)

    Okayama, 700-8558

  • Sapporo Medical University Hospital ( Site 1008)

    Sapporo, Hokkaido, 060-8543

  • Kindai University Hospital ( Site 1011)

    Sayama, Osaka, 589-8511

  • The University of Osaka Hospital ( Site 1006)

    Suita, Osaka, 565-0871

  • Tokushima University Hospital ( Site 1017)

    Tokushima, 770-8503

  • National Cancer Center Hospital ( Site 1003)

    Tokyo, 104-0045

  • Toranomon Hospital ( Site 1004)

    Tokyo, 105-8470

  • Cancer Institute Hospital of JFCR ( Site 1000)

    Tokyo, 135-8550

  • Keio University Hospital ( Site 1002)

    Tokyo, 160-8582

  • Ehime University Hospital ( Site 1014)

    Tōon, Ehime, 791-0295

  • Fujita Health University Hospital ( Site 1016)

    Toyoake, Aichi-ken, 470-1192

  • Toyama University Hospital ( Site 1013)

    Toyoma, Toyama, 930-0194

  • Yamaguchi University Hospital ( Site 1018)

    Ube, Yamaguchi, 755-8505

  • Yokohama City University Hospital ( Site 1015)

    Yokohama, Kanagawa, 236-0004

  • Kanagawa Cancer Center ( Site 1021)

    Yokohama, Kanagawa, 241-8515

Other trials in Japan

Russia11 sites

  • Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 1151)

    Krasnoyarsk, Krasnoyarsk Krai, 660133

  • SBIH City clinical hospital named after D.D. Pletniov ( Site 1160)

    Moscow, Moscow, 105077

  • N.N. Blokhin NMRCO ( Site 1156)

    Moscow, Moscow, 115478

  • Russian Scientific Center of Roentgenoradiology ( Site 1155)

    Moscow, Moscow, 117997

  • First Moscow State Medical University n.a. I.M.Sechenov ( Site 1163)

    Moscow, Moscow, 119146

  • Central Clinical Hospital with Polyclinic ( Site 1157)

    Moscow, Moscow, 121359

  • Hadassah Medical-Oncology department ( Site 1164)

    Moscow, Moscow Oblast, 121205

  • Omsk Clinical Oncology Dispensary ( Site 1150)

    Omsk, Omsk Oblast, 644013

  • Russian Scientific Center of Radiology and Surgical Technologies ( Site 1153)

    Saint Petersburg, Sankt-Peterburg, 197758

  • SBHI SPb Clinical Research Centre of specialized types of medical care ( Site 1159)

    Saint Petersburg, Sankt-Peterburg, 197758

  • City clinical oncological dispensary ( Site 1154)

    Saint Petersburg, Sankt-Peterburg, 198255

Other trials in Russia

Italy10 sites

  • Medical Oncology Ospedale San Donato ( Site 0609)

    Arezzo, 52100

  • Azienda Ospedaliera Policlinico di Bari ( Site 0610)

    Bari, 70124

  • AOU di Bologna Policlinico S Orsola Malpighi ( Site 0606)

    Bologna, 40138

  • Istituto Nazionale dei Tumori ( Site 0601)

    Milan, 20133

  • Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 0604)

    Modena, 41125

  • Istituto Oncologico Veneto IRCCS ( Site 0603)

    Padova, 35128

  • Fondazione Salvatore Maugeri clinica del lavoro ( Site 0600)

    Pavia, 27100

  • Fondazione Policlinico Universitario A. Gemelli ( Site 0607)

    Roma, 00168

  • Azienda Ospedaliera Santa Maria ( Site 0602)

    Terni, 05100

  • Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Trento-Oncology Unit ( Site 0605)

    Verona, Veneto, 37126

Other trials in Italy

United Kingdom9 sites

  • Cambridge University Hospitals NHSFT ( Site 1405)

    Cambridge, Cambridgeshire, CB2 0QQ

  • Western General Hospital ( Site 1400)

    Edinburgh, Edinburgh, City of, EH4 2XU

  • Medway Maritime Hospital ( Site 1406)

    Gillingham, ME7 5NY

  • The Beatson West of Scotland Cancer Centre ( Site 1402)

    Glasgow, Glasgow City, G12 0YN

  • Barts Health NHS Trust ( Site 1407)

    London, London, City of, EC1A 7BE

  • Royal Marsden NHS Foundation Trust ( Site 1403)

    London, London, City of, SW3 6JJ

  • Imperial Healthcare NHS Trust Charing Cross Hospital ( Site 1409)

    London, London, City of, W6 8RF

  • The Christie NHS Foundation Trust ( Site 1401)

    Manchester, M20 4BX

  • Royal Marsden Hospital Sutton-Surrey ( Site 1411)

    Sutton, London, City of, SM2 5PT

Other trials in United Kingdom

France8 sites

  • CHU Besancon - Hopital Jean Minjoz ( Site 0351)

    Besançon, Doubs, 25000

  • CHU de Bordeaux Hop St ANDRE ( Site 0359)

    Bordeaux, Aquitaine, 33075

  • Centre Francois Baclesse ( Site 0360)

    Caen, Calvados, 14075

  • Institut de Cancerologie du Gard - CHU Caremeau ( Site 0352)

    Nîmes, Gard, 30029

  • Centre Hospitalier Lyon Sud ( Site 0354)

    Pierre-Bénite, Rhone, 69310

  • Institut de cancérologie Strasbourg Europe (ICANS) ( Site 0350)

    Strasbourg, Alsace, 67200

  • Institut de Cancérologie de Lorraine Alexis Vautrin ( Site 0356)

    Vandœuvre-lès-Nancy, Lorraine, 54519

  • Gustave Roussy ( Site 0353)

    Villejuif, Val-de-Marne, 94800

Other trials in France

Germany8 sites

  • Universitaetsmedizin Berlin ( Site 0400)

    Berlin, 10117

  • Universitaetsklinikum Carl Gustav Carus Dresden ( Site 0403)

    Dresden, Saxony, 01307

  • Universitaetsklinikum Duesseldorf ( Site 0410)

    Düsseldorf, North Rhine-Westphalia, 40225

  • Universitaetsklinikum Essen ( Site 0401)

    Essen, North Rhine-Westphalia, 45122

  • Universitatsklinikum Hamburg ( Site 0408)

    Hamburg, 20246

  • Universitaetsklinikum Jena ( Site 0402)

    Jena, Thuringia, 07747

  • Universitaetsklinikum Magdeburg A.o.R. ( Site 0404)

    Magdeburg, Saxony-Anhalt, 39120

  • Universitaetsklinik fuer Urologie ( Site 0405)

    Tübingen, Baden-Wurttemberg, 72076

Other trials in Germany

Turkey (Türkiye)8 sites

  • Ankara Universitesi Tip Fakultesi ( Site 1311)

    Ankara, 06100

  • Hacettepe Universitesi Tip Fakultesi ( Site 1300)

    Ankara, 06230

  • Gazi Universitesi Tip Fakultesi ( Site 1308)

    Ankara, 06560

  • Trakya University Medical Faculty Balkan Oncology Hospital ( Site 1302)

    Edirne, 22030

  • Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 1305)

    Istanbul, 34098

  • Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 1303)

    Istanbul, 34722

  • Ege Universitesi Tip Fakultesi Hastanesi ( Site 1304)

    Izmir, 35100

  • Izmir Katip Celebi Universitesi Ataturk Egitim ve Arastirma Hastanesi ( Site 1306)

    Izmir, 35360

Other trials in Turkey (Türkiye)

Canada6 sites

  • Nova Scotia Health Authority QEII-HSC ( Site 0150)

    Halifax, Nova Scotia, B3H 1V7

  • Juravinski Cancer Centre ( Site 0154)

    Hamilton, Ontario, L8V 5C2

  • Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0151)

    Montreal, Quebec, H2X 3E4

  • Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0152)

    Québec, Quebec, G1J 1Z4

  • Sunnybrook Research Institute ( Site 0153)

    Toronto, Ontario, M4N 3M5

  • BC Cancer - Vancouver Center ( Site 0155)

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

Czechia6 sites

  • Masarykuv onkologicky ustav ( Site 0105)

    Brno, Brno-mesto, 656 53

  • Fakultni nemocnice Hradec Kralove ( Site 0106)

    Hradec Králové, 50005

  • Fakultni nemocnice Olomouc ( Site 0104)

    Olomouc, 77900

  • Fakultni nemocnice Ostrava ( Site 0103)

    Ostrava, Ostrava Mesto, 708 52

  • Fakultni nemocnice Kralovske Vinohrady ( Site 0102)

    Prague, 100 34

  • Fakultni Thomayerova nemocnice ( Site 0107)

    Prague, 140 59

Other trials in Czechia

Hungary6 sites

  • Semmelweis Egyetem ( Site 0501)

    Budapest, 1085

  • Orszagos Onkologiai Intezet ( Site 0503)

    Budapest, 1122

  • Debreceni Egyetem Klinikai Kozpont ( Site 0504)

    Debrecen, Hajdú-Bihar, 4032

  • Bekes Megyei Kozponti Korhaz - Pandy Kalman Tagkorhaza ( Site 0505)

    Gyula, Bekes County, H-5700

  • Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Okta-Klinikai Onkológiai és Sugárterápiás Ce ( Site 0502)

    Miskolc, Borsod-Abauj Zemplen county, 3526

  • Zala Megyei Szent Rafael Korhaz ( Site 0509)

    Zalaegerszeg, 8900

Other trials in Hungary

South Korea6 sites

  • Chungnam National University Hospital ( Site 1205)

    Daejeon, Taejon-Kwangyokshi, 35015

  • National Cancer Center ( Site 1204)

    Gyeonggi-do, Kyonggi-do, 10408

  • Korea University Anam Hospital ( Site 1203)

    Seoul, 02841

  • Severance Hospital Yonsei University Health System ( Site 1202)

    Seoul, 03722

  • Asan Medical Center ( Site 1200)

    Seoul, 05505

  • Samsung Medical Center ( Site 1201)

    Seoul, 06351

Other trials in South Korea

Taiwan6 sites

  • Chang Gung Medical Foundation - Kaohsiung ( Site 1104)

    Kaohsiung City, 83301

  • Taichung Veterans General Hospital ( Site 1105)

    Taichung, 407

  • National Cheng Kung University Hospital ( Site 1103)

    Tainan, 704

  • National Taiwan University Hospital ( Site 1100)

    Taipei, 10002

  • Taipei Veterans General Hospital ( Site 1101)

    Taipei, 11217

  • Chang Gung Medical Foundation-Linkou Branch-Urology ( Site 1106)

    Taoyuan, 333

Other trials in Taiwan

Brazil5 sites

  • Centro Avançado de Tratamento Oncológico- CENANTRON ( Site 1657)

    Belo Horizonte, Minas Gerais, 30130-090

  • Instituto de Cancer e Transplante de Curitiba ICTR ( Site 1650)

    Curitiba, Paraná, 80510-130

  • Liga Norte Riograndense Contra o Cancer ( Site 1651)

    Natal, Rio Grande do Norte, 59062-000

  • Hospital de Clinicas de Porto Alegre ( Site 1655)

    Porto Alegre, Rio Grande do Sul, 90035-903

  • BP - A Beneficencia Portuguesa de São Paulo ( Site 1653)

    São Paulo, São Paulo, 01323-001

Other trials in Brazil

Colombia5 sites

  • Administradora Country SA - Clinica del Country ( Site 1701)

    Bogotá, Bogota D.C., 110221

  • Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 1702)

    Bogotá, Bogota D.C., 111321

  • Fundacion Centro de Investigacion Clinica CIC ( Site 1703)

    Medellín, Antioquia, 050021

  • Oncologos del Occidente S.A. ( Site 1708)

    Pereira, Risaralda Department, 660006

  • Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 1709)

    Valledupar, Cesar Department, 200001

Other trials in Colombia

Spain5 sites

  • Hospital Universitari Vall d Hebron ( Site 1250)

    Barcelona, Catalonia, 08035

  • Instituto Catalan de Oncologia - ICO ( Site 1251)

    Barcelona, Catalonia, 08908

  • Hospital Ramon y Cajal ( Site 1253)

    Madrid, 28034

  • Hospital General Universitario 12 de Octubre ( Site 1252)

    Madrid, 28041

  • Instituto Valenciano de Oncologia - IVO ( Site 1254)

    Valencia, Valenciana, Comunitat, 46009

Other trials in Spain

Finland4 sites

  • HYKS. ( Site 0302)

    Helsinki, Uusimaa, 00290

  • Kuopion Yliopistollinen Sairaala ( Site 0304)

    Kuopio, Northern Savonia, 70210

  • Tampereen yliopistollinen sairaala ( Site 0300)

    Tampere, Pirkanmaa, 33520

  • TYKS T-sairaala Syopatautien pkl ( Site 0301)

    Turku, Southwest Finland, 20520

Other trials in Finland

Hong Kong4 sites

  • Queen Mary Hospital ( Site 1051)

    Hong Kong, 000000

  • Prince of Wales Hospital ( Site 1050)

    Hong Kong

  • Queen Elizabeth Hospital. ( Site 1052)

    Kowloon

  • Princess Margaret Hospital. ( Site 1053)

    Lai Chi Kok

Other trials in Hong Kong

Sweden4 sites

  • Laenssjukhuset Ryhov ( Site 1853)

    Jönköping, Jönköping County, 551 85

  • Malmo Universitetssjukhus ( Site 1851)

    Malmö, Skåne County, 214 28

  • Karolinska Universitetssjukhuset Solna ( Site 1850)

    Stockholm, Stockholm County, 171 76

  • Norrlands Universitetssjukhus ( Site 1856)

    Umeå, Västerbotten County, 901 85

Other trials in Sweden

Ukraine3 sites

  • ME І.І. Mechnykov Dnipro Regional Clinical Hospital ( Site 1453)

    Dnipropetrovsk, Dnipropetrovsk Oblast, 49005

  • MI Precarpathian Clinical Oncology Center ( Site 1452)

    Ivano-Frankivsk, Ivano-Frankivsk Oblast, 76018

  • Kyiv City Clinical Oncology Center ( Site 1450)

    Kyiv, 03115

Other trials in Ukraine

Chile2 sites

  • Bradfordhill ( Site 0003)

    Santiago, Region M. de Santiago, 8420383

  • Centro Investigación del Cáncer James Lind ( Site 0004)

    Temuco, Araucania, 4800827

Other trials in Chile

Denmark2 sites

  • Aarhus University Hospital Skejby ( Site 0250)

    Aarhus, Central Jutland, 8200

  • Herlev Hospital ( Site 0251)

    Herlev, Capital Region, 2730

Other trials in Denmark

Norway2 sites

  • Helse Bergen HF - Haukeland Universitetssykehus ( Site 0854)

    Bergen, Hordaland, 5021

  • Akershus universitetssykehus ( Site 0851)

    Lorenskog, Akershus, 1478

Other trials in Norway

About this study

Official title: 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.

Read the 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.

Being tested
Belzutifan, Everolimus
Keywords
Hypoxia inducible Factor (HIF), 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, PT-2977, PT2977, MK6482
Medical subject headings
Carcinoma, Renal Cell, Kidney Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BelzutifanDrug

    Also called MK-6482, WELIREG™

    Oral tablets

  • EverolimusDrug

    Also called Afinitor, Afinitor DISPERZ, Zortress

    Oral tablets

Study groups in NCT04195750
Study groupRoleWhat they receive
BelzutifanExperimentalRandomized participants received 120 mg of belzutifan orally once daily (QD), until disease progression or discontinuation.
Receives: Drug: Belzutifan
EverolimusActive comparatorRandomized participants received 10 mg of Everolimus orally QD, until disease progression or discontinuation.
Receives: Drug: Everolimus
Safety Run-InExperimentalNon-Randomized participants enrolled into the Safety Run-in received up to 120 mg of belzutifan QD.
Receives: Drug: Belzutifan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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 is presented here.

    Measured: Up to approximately 39 months

  2. Overall Survival (OS)

    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.

    Measured: Up to approximately 49 months

Secondary outcomes (11)

  1. 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 is presented here.

    Measured: Up to approximately 31 months

  2. 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 is presented here. The Median DOR was analyzed by the Kaplan-Meier method for censored data.

    Measured: Up to approximately 49 months

  3. 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.

    Measured: Up to approximately 78 months

  4. 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.

    Measured: Up to approximately 78 months

  5. 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

    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.

    Measured: Up to approximately 39 months

  6. TTD in Physical Functioning Using the EORTC QLQ-C30 Items 1- 5 Score

    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.

    Measured: Up to approximately 39 months

  7. 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 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.

    Measured: Up to approximately 39 months

  8. Change From Baseline to Week 17 in the HRQoL Using the EORTC QLQ-C30 Items 29 and 30 Combined Score

    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.

    Measured: Baseline (Day 1) and week 17

  9. Change From Baseline to Week 17 in Physical Functioning Using the EORTC QLQ-C30 Items 1- 5 Score

    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.

    Measured: Baseline (Day 1) and week 17

  10. Change From Baseline to Week 17 in Disease Symptoms Using the FKSI-DRS Items 1-9 Score

    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.

    Measured: Baseline (Day 1) and week 17

  11. 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

    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.

    Measured: Baseline (Day 1) and week 17

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Dec 2019
  2. Study start27 Feb 2020
  3. Primary completion15 Apr 2024
  4. Study completion14 Oct 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
755 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04195750
Sponsor's protocol ID
6482-005
Other IDs
MK-6482, 205262, jRCT2080225166, 2023-506635-15-00, U1111-1294-1321, 2019-003444-72, 2019, 2023
Status last verified
Sep 2026
First submitted
10 Dec 2019
Last updated
20 Oct 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

  • Choueiri TK, Powles T, Peltola K, de Velasco G, Burotto M, Suarez C, Ghatalia P, Iacovelli R, Lam ET, Verzoni E, Gumus M, Stadler WM, Kollmannsberger C, Melichar B, Venugopal B, Gross-Goupil M, Poprach A, De Santis M, Schutz FA, Park SH, Nosov DA, Porta C, Lee JL, Garcia-Del-Muro X, Biscaldi E, Manneh Kopp R, Oya M, He L, Wang A, Perini RF, Vickery D, Albiges L, Rini B; LITESPARK-005 Investigators. Belzutifan versus Everolimus for Advanced Renal-Cell Carcinoma. N Engl J Med. 2024 Aug 22;391(8):710-721. doi: 10.1056/NEJMoa2313906.

    PubMed 39167807

  • Powles T, Choueiri TK, Albiges L, Peltola K, de Velasco G, Burotto M, Suarez C, Ghatalia P, Iacovelli R, Lam ET, Verzoni E, Gumus M, Stadler WM, Kollmannsberger C, Melichar B, Venugopal B, Gross-Goupil M, Poprach A, De Santis M, Rizzo M, Shinde R, Saretsky TL, He L, Perini RF, Vickery D, Rini B. Health-related quality of life with belzutifan versus everolimus for advanced renal cell carcinoma (LITESPARK-005): patient-reported outcomes from a randomised, open-label, phase 3 trial. Lancet Oncol. 2025 Apr;26(4):491-502. doi: 10.1016/S1470-2045(25)00032-4. Epub 2025 Mar 17.

    PubMed 40112850

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Belzutifan and Everolimus in people with Carcinoma, Renal Cell, run by Merck Sharp & Dohme LLC at 172 sites in 23 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 20 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 172 sites in United States, Japan, Russia, Italy, United Kingdom and 18 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04195750, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2026.

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