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

Carcinoma, Renal Cell Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04195750
• Other study ID #: 6482-005
• Secondary ID: MK-6482205262jRC
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 27, 2020
• Est. completion date: September 17, 2025

Study information

• Verified date: April 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). The hypothesis is that belzutifan is superior to everolimus with respect to PFS and OS.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 736
• Est. completion date: September 17, 2025
• Est. primary completion date: September 17, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 2a (HIF-2a 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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell

Intervention

Drug:
• Belzutifan
Oral tablets
• Everolimus
Oral tablets

Locations

Country	Name	City	State
Brazil	Centro Avancado de Tratamento Oncologico ( Site 1657)	Belo Horizonte	Minas Gerais
Brazil	Instituto de Cancer e Transplante de Curitiba ICTR ( Site 1650)	Curitiba	Parana
Brazil	Liga Norte Riograndense Contra o Cancer ( Site 1651)	Natal	Rio Grande Do Norte
Brazil	Hospital de Clinicas de Porto Alegre ( Site 1655)	Porto Alegre	Rio Grande Do Sul
Brazil	Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 1653)	Sao Paulo
Canada	Nova Scotia Health Authority QEII-HSC ( Site 0150)	Halifax	Nova Scotia
Canada	Juravinski Cancer Centre ( Site 0154)	Hamilton	Ontario
Canada	Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0151)	Montreal	Quebec
Canada	CHUQ-Univ Laval-Hotel Dieu de Quebec ( Site 0152)	Quebec
Canada	Sunnybrook Research Institute ( Site 0153)	Toronto	Ontario
Canada	BC Cancer - Vancouver Center ( Site 0155)	Vancouver	British Columbia
Chile	Bradfordhill ( Site 0003)	Santiago	Region M. De Santiago
Chile	Centro Investigación del Cáncer James Lind ( Site 0004)	Temuco	Araucania
Colombia	Administradora Country SA - Clinica del Country ( Site 1701)	Bogota	Distrito Capital De Bogota
Colombia	Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 1702)	Bogota	Cundinamarca
Colombia	Fundacion Centro de Investigacion Clinica CIC ( Site 1703)	Medellin	Antioquia
Colombia	Oncologos del Occidente S.A. ( Site 1708)	Pereira	Risaralda
Colombia	Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 1709)	Valledupar	Cesar
Czechia	Masarykuv onkologicky ustav ( Site 0105)	Brno	Brno-mesto
Czechia	Fakultni nemocnice Hradec Kralove ( Site 0106)	Hradec Kralove
Czechia	Fakultni nemocnice Olomouc ( Site 0104)	Olomouc
Czechia	Fakultni nemocnice Ostrava ( Site 0103)	Ostrava	Ostrava Mesto
Czechia	Fakultni nemocnice Kralovske Vinohrady ( Site 0102)	Praha 10
Czechia	Fakultni Thomayerova nemocnice ( Site 0107)	Praha 4
Denmark	Aarhus University Hospital Skejby ( Site 0250)	Aarhus	Midtjylland
Denmark	Herlev Hospital ( Site 0251)	Herlev	Hovedstaden
Finland	HYKS. ( Site 0302)	Helsinki	Uusimaa
Finland	Kuopion Yliopistollinen Sairaala ( Site 0304)	Kuopio	Pohjois-Savo
Finland	Tampereen yliopistollinen sairaala ( Site 0300)	Tampere	Pirkanmaa
Finland	TYKS T-sairaala Syopatautien pkl ( Site 0301)	Turku	Varsinais-Suomi
France	CHU Besancon - Hopital Jean Minjoz ( Site 0351)	Besancon	Doubs
France	CHU de Bordeaux Hop St ANDRE ( Site 0359)	Bordeaux	Aquitaine
France	Centre Francois Baclesse ( Site 0360)	Caen	Calvados
France	Institut de Cancerologie du Gard - CHU Caremeau ( Site 0352)	Nimes	Gard
France	Centre Hospitalier Lyon Sud ( Site 0354)	Pierre Benite	Rhone
France	Institut de cancérologie Strasbourg Europe (ICANS) ( Site 0350)	Strasbourg	Bas-Rhin
France	Centre Alexis Vautrin Institut de Cancerologie de Lorraine ( Site 0356)	Vandoeuvre les Nancy	Meurthe-et-Moselle
France	Gustave Roussy ( Site 0353)	Villejuif	Val-de-Marne
Germany	Universitaetsmedizin Berlin ( Site 0400)	Berlin
Germany	Universitaetsklinikum Carl Gustav Carus Dresden ( Site 0403)	Dresden	Sachsen
Germany	Universitaetsklinikum Duesseldorf ( Site 0410)	Duesseldorf	Nordrhein-Westfalen
Germany	Universitaetsklinikum Essen ( Site 0401)	Essen	Nordrhein-Westfalen
Germany	Universitatsklinikum Hamburg-Eppendorf ( Site 0408)	Hamburg
Germany	Universitaetsklinikum Jena ( Site 0402)	Jena	Thuringen
Germany	Universitaetsklinikum Magdeburg A.o.R. ( Site 0404)	Magdeburg	Sachsen-Anhalt
Germany	Universitaetsklinik fuer Urologie ( Site 0405)	Tuebingen	Baden-Wurttemberg
Hong Kong	Prince of Wales Hospital ( Site 1050)	Hong Kong
Hong Kong	Queen Mary Hospital ( Site 1051)	Hong Kong
Hong Kong	Queen Elizabeth Hospital. ( Site 1052)	Kowloon
Hong Kong	Princess Margaret Hospital. ( Site 1053)	Lai Chi Kok
Hungary	Orszagos Onkologiai Intezet ( Site 0503)	Budapest
Hungary	Semmelweis Egyetem ( Site 0501)	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont ( Site 0504)	Debrecen
Hungary	Bekes Megyei Kozponti Korhaz - Pandy Kalman Tagkorhaza ( Site 0505)	Gyula	Bekes
Hungary	Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Okta-Klinikai Onkológiai és Sugárterápiás Ce	Miskolc	Borsod-Abauj-Zemplen
Hungary	Zala Megyei Szent Rafael Korhaz ( Site 0509)	Zalaegerszeg
Italy	Medical Oncology Ospedale San Donato ( Site 0609)	Arezzo
Italy	Azienda Ospedaliera Policlinico di Bari ( Site 0610)	Bari
Italy	Policlinico S. Orsola-Malpighi ( Site 0606)	Bologna
Italy	Istituto Nazionale dei Tumori ( Site 0601)	Milano
Italy	Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 0604)	Modena
Italy	Istituto Oncologico Veneto IRCCS ( Site 0603)	Padova	Veneto
Italy	Fondazione Salvatore Maugeri clinica del lavoro ( Site 0600)	Pavia
Italy	Fondazione Policlinico Universitario A. Gemelli ( Site 0607)	Roma
Italy	Azienda Ospedaliera Santa Maria ( Site 0602)	Terni
Italy	Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Trento-Oncology Unit ( Site 0605	Verona	Veneto
Japan	Kyushu University Hospital ( Site 1007)	Fukuoka
Japan	Hamamatsu University Hospital ( Site 1005)	Hamamatsu	Shizuoka
Japan	Saitama Medical University International Medical Center ( Site 1012)	Hidaka-city	Saitama
Japan	Hiroshima University Hospital-Hiroshima University Hospital ( Site 1019)	Hiroshima
Japan	Nara Medical University Hospital ( Site 1009)	Kashihara	Nara
Japan	National Cancer Center Hospital East ( Site 1001)	Kashiwa	Chiba
Japan	Niigata University Medical & Dental Hospital ( Site 1022)	Niigata
Japan	Okayama University Hospital ( Site 1020)	Okayama
Japan	Kindai University Hospital- Osakasayama Campus-Urology ( Site 1011)	Osakasayama	Osaka
Japan	Sapporo Medical University Hospital ( Site 1008)	Sapporo	Hokkaido
Japan	Osaka University Hospital ( Site 1006)	Suita	Osaka
Japan	Tokushima University Hospital-Department of Urology ( Site 1017)	Tokushima
Japan	Keio University Hospital ( Site 1002)	Tokyo
Japan	National Cancer Center Hospital ( Site 1003)	Tokyo
Japan	Nippon Medical School Hospital ( Site 1010)	Tokyo
Japan	The Cancer Institute Hospital of JFCR ( Site 1000)	Tokyo
Japan	Toranomon Hospital ( Site 1004)	Tokyo
Japan	Ehime University Hospital ( Site 1014)	Toon	Ehime
Japan	Fujita Health University ( Site 1016)	Toyoake	Aichi
Japan	Toyama University Hospital ( Site 1013)	Toyoma	Toyama
Japan	Yamaguchi University Hospital ( Site 1018)	Ube	Yamaguchi
Japan	Kanagawa cancer center ( Site 1021)	Yokohama	Kanagawa
Japan	Yokohama City University Hospital ( Site 1015)	Yokohama	Kanagawa
Korea, Republic of	Chungnam National University Hospital ( Site 1205)	Daejeon	Taejon-Kwangyokshi
Korea, Republic of	National Cancer Center ( Site 1204)	Gyeonggi-do	Kyonggi-do
Korea, Republic of	Asan Medical Center ( Site 1200)	Seoul
Korea, Republic of	Korea University Anam Hospital ( Site 1203)	Seoul
Korea, Republic of	Samsung Medical Center ( Site 1201)	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System ( Site 1202)	Seoul
Norway	Helse Bergen HF - Haukeland Universitetssykehus ( Site 0854)	Bergen	Hordaland
Norway	Akershus universitetssykehus ( Site 0851)	Lorenskog	Akershus
Russian Federation	Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 1151)	Krasnoyarsk	Krasnoyarskiy Kray
Russian Federation	Central Clinical Hospital with Polyclinic ( Site 1157)	Moscow	Moskva
Russian Federation	First Moscow State Medical University n.a. I.M.Sechenov ( Site 1163)	Moscow	Moskva
Russian Federation	Hadassah Medical-Oncology department ( Site 1164)	Moscow	Moskovskaya Oblast
Russian Federation	N.N. Blokhin NMRCO ( Site 1156)	Moscow	Moskva
Russian Federation	Russian Scientific Center of Roentgenoradiology ( Site 1155)	Moscow	Moskva
Russian Federation	SBIH City clinical hospital named after D.D. Pletniov ( Site 1160)	Moscow	Moskva
Russian Federation	Omsk Clinical Oncology Dispensary ( Site 1150)	Omsk	Omskaya Oblast
Russian Federation	SBHI SPb Clinical Research Centre of specialized types of medical care ( Site 1159)	Saint-Petersburg	Sankt-Peterburg
Russian Federation	City clinical oncological dispensary ( Site 1154)	Sankt-Petersburg	Sankt-Peterburg
Russian Federation	Russian Scientific Center of Radiology and Surgical Technologies ( Site 1153)	St. Petersburg	Sankt-Peterburg
Spain	Hospital Universitari Vall d Hebron ( Site 1250)	Barcelona	Cataluna
Spain	Instituto Catalan de Oncologia - ICO ( Site 1251)	L Hospitalet De Llobregat	Barcelona
Spain	Hospital General Universitario 12 de Octubre ( Site 1252)	Madrid	Madrid, Comunidad De
Spain	Hospital Ramon y Cajal ( Site 1253)	Madrid
Spain	Instituto Valenciano de Oncologia - IVO ( Site 1254)	Valencia	Valenciana, Comunitat
Sweden	Laenssjukhuset Ryhov ( Site 1853)	Jönköping	Jonkopings Lan
Sweden	Malmo Universitetssjukhus ( Site 1851)	Malmo	Skane Lan
Sweden	Karolinska Universitetssjukhuset Solna ( Site 1850)	Stockholm	Stockholms Lan
Sweden	Norrlands Universitetssjukhus ( Site 1856)	Umeå	Vasterbottens Lan
Taiwan	Chang Gung Medical Foundation - Kaohsiung ( Site 1104)	Kaohsiung
Taiwan	Taichung Veterans General Hospital ( Site 1105)	Taichung
Taiwan	National Cheng Kung University Hospital ( Site 1103)	Tainan
Taiwan	National Taiwan University Hospital ( Site 1100)	Taipei
Taiwan	Taipei Veterans General Hospital ( Site 1101)	Taipei
Taiwan	Chang Gung Medical Foundation-Linkou Branch-Urology ( Site 1106)	Taoyuan
Turkey	Ankara Universitesi Tip Fakultesi ( Site 1311)	Ankara
Turkey	Gazi Universitesi Tip Fakultesi ( Site 1308)	Ankara
Turkey	Hacettepe Universitesi Tip Fakultesi ( Site 1300)	Ankara
Turkey	Trakya University Medical Faculty Balkan Oncology Hospital ( Site 1302)	Edirne
Turkey	Göztepe Prof. Dr. Süleyman Yalçin Sehir Hastanesi-oncology ( Site 1303)	Istanbul
Turkey	Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 1305)	Istanbul
Turkey	Ege Universitesi Tip Fakultesi Hastanesi ( Site 1304)	Izmir
Turkey	Izmir Katip Celebi Universitesi Ataturk Egitim ve Arastirma Hastanesi ( Site 1306)	Izmir
Ukraine	MI Dnipr Regional Clinical Hospital named after I.I. Mechnikov ( Site 1453)	Dnipropetrovsk	Dnipropetrovska Oblast
Ukraine	MI Precarpathian Clinical Oncology Center ( Site 1452)	Ivano-Frankivsk	Ivano-Frankivska Oblast
Ukraine	Kyiv City Clinical Oncology Center ( Site 1450)	Kyiv	Kyivska Oblast
United Kingdom	Cambridge University Hospitals NHSFT ( Site 1405)	Cambridge	Cambridgeshire
United Kingdom	Western General Hospital ( Site 1400)	Edinburgh	Edinburgh, City Of
United Kingdom	Medway Maritime Hospital ( Site 1406)	Gillingham
United Kingdom	The Beatson West of Scotland Cancer Centre ( Site 1402)	Glasgow	Glasgow City
United Kingdom	Barts Health NHS Trust ( Site 1407)	London	London, City Of
United Kingdom	Imperial Healthcare NHS Trust Charing Cross Hospital ( Site 1409)	London	London, City Of
United Kingdom	Royal Marsden NHS Foundation Trust ( Site 1403)	London	London, City Of
United Kingdom	The Christie NHS Foundation Trust ( Site 1401)	Manchester
United Kingdom	Royal Marsden Hospital Sutton-Surrey ( Site 1411)	Sutton	Surrey
United States	University Of Colorado ( Site 1540)	Aurora	Colorado
United States	Texas Oncology-Austin Central ( Site 1533)	Austin	Texas
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 1514)	Baltimore	Maryland
United States	St. Vincent Frontier Cancer Center ( Site 1549)	Billings	Montana
United States	University of Alabama - Birmingham ( Site 1538)	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center ( Site 1501)	Boston	Massachusetts
United States	Dana Farber Cancer Institute ( Site 1505)	Boston	Massachusetts
United States	Massachusetts General Hospital ( Site 1558)	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill ( Site 1537)	Chapel Hill	North Carolina
United States	Medical University of South Carolina ( Site 1518)	Charleston	South Carolina
United States	The University of Chicago Medical Center ( Site 1539)	Chicago	Illinois
United States	Oncology Hematology Care, Inc. ( Site 1524)	Cincinnati	Ohio
United States	Cleveland Clinic ( Site 1504)	Cleveland	Ohio
United States	Texas Oncology, P.A.-Dallas ( Site 1534)	Dallas	Texas
United States	Henry Ford Cancer Center ( Site 1511)	Detroit	Michigan
United States	John Theurer Cancer Center at Hackensack University Medical Center ( Site 1513)	Hackensack	New Jersey
United States	Hattiesburg Clinic ( Site 1509)	Hattiesburg	Mississippi
United States	UCHealth Highlands Ranch Hospital ( Site 1560)	Highlands Ranch	Colorado
United States	University of California San Diego Moores Cancer Center ( Site 1546)	La Jolla	California
United States	Northwest Georgia Oncology Centers PC ( Site 1520)	Marietta	Georgia
United States	Henry Joyce Cancer Clinic ( Site 1544)	Nashville	Tennessee
United States	Ochsner Medical Center ( Site 1522)	New Orleans	Louisiana
United States	Abramson Cancer Center ( Site 1525)	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center ( Site 1506)	Philadelphia	Pennsylvania
United States	Oregon Health & Science University ( Site 1553)	Portland	Oregon
United States	University of Rochester Medical Center ( Site 1543)	Rochester	New York
United States	St Joseph Heritage Healthcare ( Site 1531)	Santa Rosa	California
United States	Oklahoma Cancer Specialists and Research Institute, LLC ( Site 1523)	Tulsa	Oklahoma
United States	Sibley Memorial Hospital ( Site 1559)	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  Chile,  Colombia,  Czechia,  Denmark,  Finland,  France,  Germany,  Hong Kong,  Hungary,  Italy,  Japan,  Korea, Republic of,  Norway,  Russian Federation,  Spain,  Sweden,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Overall Survival (OS)	Time from randomization to death due to any cause	Up to approximately 49 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary