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NCT07227402PHASE3Recruiting

A Clinical Study of Belzutifan and Zanzalintinib in People With Recurrent Kidney Cancer Following Adjuvant Therapy (MK-6482-033)

Merck Sharp & Dohme LLC

Start Date

11/26/2025

Completion Date

2/27/2032

Summary

Researchers are looking for more ways to treat advanced renal cell carcinoma (RCC) that is recurrent. Researchers want to learn if recurrent advanced renal cell carcinoma (RCC) responds (gets smaller or goes away) after treatment with belzutifan (MK-6482) and zanzalintinib compared to cabozantinib. The goal of this study is to learn if: People who take belzutifan and zanzalintinib live longer overall and without the cancer getting worse than people who take cabozantinib.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Has a histologically confirmed diagnosis of unresectable, advanced renal cell cancer (RCC) with clear cell component (with or without sarcomatoid features) i.e., Stage IV renal cell cancer per American Joint Committee on Cancer (AJCC) (8th Edition) * Has measurable disease per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) * Has disease recurrence during adjuvant anti-programmed cell death 1/programmed cell death ligand 1 (PD-1/L1) therapy or recurrence ≤24 months following the last dose of adjuvant anti-PD-1/L1 therapy * Has received no other prior systemic therapy for their RCC except for their adjuvant anti-PD-1/L1 therapy Exclusion Criteria: The main exclusion criteria include but are not limited to the following: * Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, new-onset angina, pulmonary embolism, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability * Had deep vein thrombosis within 3 months before randomization unless stable, asymptomatic, and treated with therapeutic anticoagulation for at least 4 weeks before randomization * Has a left ventricular ejection fraction ≤50% or below the institutional (or local laboratory) normal range as determined by multigated acquisition or echocardiogram * Has had major surgery within 8 weeks before randomization or has not adequately recovered from major surgery or has ongoing surgical complications * Has current pneumonitis/interstitial lung disease * Has symptomatic pleural effusion (for example cough, dyspnea, pleuritic chest pain), ascites, or pericardial fluid requiring drainage within 4 weeks prior to randomization * Has a gastrointestinal disorder including those associated with a high risk of perforation or fistula formation * Has a serious active nonhealing wound/ulcer/bone fracture * Has a requirement for hemodialysis or peritoneal dialysis * Has history of human immunodeficiency virus infection * Has hepatitis B or hepatitis C virus * Has pharmacologically uncompensated, symptomatic hypothyroidism * Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention

Interventions

DRUG

Belzutifan

DRUG

Zanzalintinib

DRUG

Cabozantinib

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Conditions

Renal Cell Carcinoma

Locations

Alaska Oncology and Hematology ( Site 0133)

Anchorage, Alaska 99508

United States

Providence Medical Foundation ( Site 0141)

Fullerton, California 92835

United States

Cedars-Sinai Medical Center ( Site 0112)

Los Angeles, California 90048

United States

New England Cancer Specialists ( Site 0132)

Westbrook, Maine 04092

United States

Greater Baltimore Medical Center ( Site 0145)

Baltimore, Maryland 21204

United States

Metro-Minnesota Community Clinical Oncology ( Site 0144)

Saint Louis Park, Minnesota 55426

United States

Oncology Hematology West P.C. dba Nebraska Cancer Specialists ( Site 0131)

Omaha, Nebraska 68130-2042

United States

Carolina Oncology Specialists, PA ( Site 9002)

Charlotte, North Carolina 28207

United States

Thompson Cancer Survival Center ( Site 0125)

Knoxville, Tennessee 37916

United States

Hospital Aleman ( Site 0204)

CABA, Buenos Aires C1118AAT

Argentina

Hospital Italiano de Buenos Aires. ( Site 0203)

Caba, Buenos Aires C1199ABB

Argentina

Asociación de Beneficencia Hospital Sirio Libanés ( Site 0205)

Caba, Buenos Aires C1419AHN

Argentina

Instituto Alexander Fleming ( Site 0202)

CABA, Buenos Aires C1426ANZ

Argentina

Hospital Universitario Austral ( Site 0212)

Pilar, Buenos Aires B1629AHJ

Argentina

Centro de Educación Médica e Investigaciones clínicas "Dr. Norberto Quirno" (CEMIC) ( Site 0208)

Caba., Buenos Aires F.D. C1431FWO

Argentina

Sanatorio Parque ( Site 0201)

Rosario, Santa Fe Province S2000DSV

Argentina

Instituto de Oncología de Rosario ( Site 0209)

Rosario, Santa Fe Province S2000KZE

Argentina

Hospital Privado Universitario de Córdoba ( Site 0207)

Córdoba, X5016KEH

Argentina

Macquarie University-MQ Health Clinical Trials Unit ( Site 2100)

Sydney, New South Wales 2109

Australia

Ordensklinikum Linz GmbH Elisabethinen-Urologie ( Site 0600)

Linz, Upper Austria 4020

Austria

Medizinische Universitat Wien ( Site 0601)

Vienna, 1090

Austria

Cliniques Universitaires Saint-Luc ( Site 0703)

Brussels, Bruxelles-Capitale, Region de 1200

Belgium

Ziekenhuis Oost-Limburg, Campus St.-Jan ( Site 0701)

Genk, Limburg 3600

Belgium

UZ Gent ( Site 0702)

Ghent, Oost-Vlaanderen 9000

Belgium

UZ Leuven ( Site 0700)

Leuven, Vlaams-Brabant 3000

Belgium

IPC - MT Instituto de Pesquisas Clínicas do Mato Grosso ( Site 0305)

Cuiabá, Mato Grosso 78020-500

Brazil

Liga Norte Riograndense Contra o Câncer ( Site 0307)

Natal, Rio Grande do Norte 59062-000

Brazil

Hospital Moinhos de Vento ( Site 0309)

Porto Alegre, Rio Grande do Sul 90560-032

Brazil

Fundação Faculdade Regional de Medicina de São José do Rio Preto ( Site 0302)

São José do Rio Preto, São Paulo 15090-000

Brazil

Hospital Alemao Oswaldo Cruz ( Site 0311)

São Paulo, São Paulo 01327-001

Brazil

Oncocentro Valdivia ( Site 0408)

Valdivia, Los Ríos Region 5112129

Chile

Fundacion Arturo Lopez Perez ( Site 0401)

Santiago, Region M. de Santiago 7500921

Chile

Centro de Investigacion Clinica UC CICUC ( Site 0402)

Santiago, Region M. de Santiago 833000

Chile

Klinički bolnički centar Sestre milosrdnice ( Site 0801)

Zagreb, City of Zagreb 10000

Croatia

Klinički bolnički centar Zagreb ( Site 0800)

Zagreb, City of Zagreb 10000

Croatia

Klinički Bolnički Centar Split ( Site 0802)

Split, Split-Dalmatia County 21000

Croatia

Masarykuv onkologicky ustav ( Site 0903)

Brno, Brno-mesto 656 53

Czechia

Fakultni nemocnice Ostrava ( Site 0904)

Ostrava, Ostrava Mesto 708 52

Czechia

Nemocnice České Budějovice ( Site 0905)

České Budějovice, 370 01

Czechia

Fakultni nemocnice Hradec Kralove ( Site 0902)

Hradec Králové, 500 05

Czechia

Fakultni nemocnice Olomouc ( Site 0901)

Olomouc, 779 00

Czechia

Vseobecna fakultni nemocnice v Praze ( Site 0906)

Prague, 128 08

Czechia

Fakultni nemocnice v Motole ( Site 0900)

Prague, 150 06

Czechia

Herlev Hospital ( Site 1002)

Herlev, Capital Region 2730

Denmark

Aarhus University Hospital Skejby ( Site 1001)

Aarhus, Central Jutland 8200

Denmark

Odense Universitetshospital ( Site 1000)

Odense, Region Syddanmark 9000

Denmark

CHU de Bordeaux Hop St ANDRE ( Site 1115)

Bordeaux, Gironde 33075

France

Hôpital Foch ( Site 1118)

Suresnes, Hauts-de-Seine 92150

France

Centre de Cancérologie du Grand Montpellier ( Site 1112)

Montpellier, Herault 34070

France

CHU GRENOBLE ALPES ( Site 1101)

La Tronche, Isere 38700

France

Centre d'Oncologie de Gentilly ( Site 1117)

Nancy, Lorraine 54100

France

Centre Hospitalier Universitaire d'Angers-Urology ( Site 1104)

Angers, Pays de la Loire Region 49933

France

Centre Hospitalier de la Cote Basque ( Site 1113)

Bayonne, Pyrenees-Atlantiques 64109

France

centre hospitalier lyon sud ( Site 1102)

Pierre-Bénite, Rhone 69310

France

CHU de Rouen ( Site 1108)

Rouen, Seine-Maritime 76031

France

HENRI MONDOR HOSPITAL ( Site 1116)

Créteil, Val-de-Marne 94010

France

CHD Vendee ( Site 1103)

La Roche-sur-Yon, Vendee 85000

France

Klinikum Stuttgart - Katharinenhospital ( Site 1201)

Stuttgart, Baden-Wurttemberg 70174

Germany

UniversitaetsklInikum Tuebingen ( Site 1207)

Tübingen, Baden-Wurttemberg 72076

Germany

Universitätsmedizin Göttingen - Georg-August-Universität ( Site 1211)

Göttingen, Lower Saxony 37075

Germany

Helios Kliniken Schwerin GmbH ( Site 1206)

Schwerin, Mecklenburg-Vorpommern 19055

Germany

Marienhospital Herne ( Site 1215)

Herne, North Rhine-Westphalia 44625

Germany

Universitaetsklinikum Muenster ( Site 1202)

Münster, North Rhine-Westphalia 70174

Germany

Universitaetsklinikum Carl Gustav Carus Dresden ( Site 1213)

Dresden, Saxony 01307

Germany

HELIOS Klinikum Erfurt ( Site 1208)

Erfurt, Thuringia 99089

Germany

Universitätsklinikum Jena ( Site 1204)

Jena, Thuringia 07747

Germany

Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 1203)

Berlin, 10117

Germany

Universitaetsklinikum Hamburg-Eppendorf ( Site 1214)

Hamburg, 20246

Germany

Alexandra General Hospital of Athens ( Site 1300)

Athens, Attica 115 28

Greece

Metropolitan Hospital ( Site 1302)

Athens, Attica 185 47

Greece

University General Hospital ''Attikon'' - General Hospital of West Attica "H AGIA VARVARA" ( Site 1301)

Chaïdári, Attica 124 62

Greece

Prince of Wales Hospital ( Site 2200)

Hong Kong,

Hong Kong

Queen Mary Hospital ( Site 2201)

Hong Kong,

Hong Kong

Cork University Hospital ( Site 1501)

Cork, T12 YK23

Ireland

Tallaght University Hospital ( Site 1500)

Dublin, D24 NR0A

Ireland

Azienda Ospedaliera Di Rilievo Nazionale A. Cardarelli ( Site 1609)

Naples, Campania 80131

Italy

Istituto Nazionale Tumori Regina Elena ( Site 1611)

Rome, Lazio 00144

Italy

Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 1600)

Milan, Milano 20133

Italy

Istituto Clinico Humanitas ( Site 1613)

Rozzano, Milano 20089

Italy

Azienda Ospedaliera S. Luigi Gonzaga ( Site 1607)

Orbassano, Piedmont 10043

Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore ( Site 1601)

Rome, Roma 00618

Italy

Azienda Ospedaliera Universitaria Careggi ( Site 1608)

Florence, Tuscany 50134

Italy

Istituto Oncologico Veneto IRCCS ( Site 1612)

Castelfranco Veneto, Veneto 31033

Italy

Casa di Cura Dott. Pederzoli - UO Oncologia ( Site 1610)

Peschiera del Garda, Veneto 37019

Italy

Azienda USL 8 di Arezzo ( Site 1605)

Arezzo, 52100

Italy

A.O.U.C. Policlinico di Bari ( Site 1602)

Bari, 70124

Italy

IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola ( Site 1604)

Bologna, 40138

Italy

Ospedale San Martino ( Site 1606)

Genova, 16132

Italy

CIO - Centro de Inmuno-Oncología de Occidente ( Site 0503)

Guadalajara, Jalisco 44630

Mexico

I CAN ONCOLOGY CENTER S.A. DE C.V. ( Site 0507)

Monterrey, Nuevo León 64710

Mexico

Centro de Investigacion Clinica de Oaxaca ( Site 0502)

Oaxaca City, Oaxaca 68020

Mexico

Higiea Oncologia ( Site 0504)

Mexico City, 11810

Mexico

Clinica Integral Internacional de Oncología ( Site 0506)

Puebla City, 72530

Mexico

AIDPORT Sp. z o.o. ( Site 1716)

Skórzewo, Greater Poland Voivodeship 60-185

Poland

Zakład Diagnostyki Laboratoryjnej, Centrum Onkologii ( Site 1707)

Bydgoszcz, Kuyavian-Pomeranian Voivodeship 85-796

Poland

Pratia MCM Krakow ( Site 1713)

Krakow, Lesser Poland Voivodeship 30-727

Poland

Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie ( Site 1703)

Krakow, Lesser Poland Voivodeship 31-826

Poland

Mazowiecki Szpital Wojewódzki w Siedlcach-Siedleckie Centrum Onkologii ( Site 1702)

Siedlce, Masovian Voivodeship 08-110

Poland

MTZ Clinical Research Powered by Pratia ( Site 1705)

Warsaw, Masovian Voivodeship 02-172

Poland

Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 1710)

Przemyśl, Podkarpackie Voivodeship 37-700

Poland

Szpital Wojewodzki im. Mikolaja Kopernika w Koszalinie ( Site 1701)

Koszalin, West Pomeranian Voivodeship 75-581

Poland

National University Hospital ( Site 2400)

Singapore, Central Singapore 119074

Singapore

National Cancer Centre Singapore ( Site 2401)

Singapore, Central Singapore 168583

Singapore

Chonnam National University Hwasun Hospital ( Site 2505)

Hwasun-gun, Jeonranamdo 58128

South Korea

Seoul National University Bundang Hospital ( Site 2504)

Seongnam, Kyonggi-do 13620

South Korea

Chungnam National University Hospital ( Site 2506)

Taejŏn, Taejon-Kwangyokshi 35015

South Korea

Severance Hospital, Yonsei University Health System ( Site 2503)

Seoul, 03722

South Korea

Asan Medical Center ( Site 2501)

Seoul, 05505

South Korea

Samsung Medical Center ( Site 2502)

Seoul, 06351

South Korea

Institut Català d'Oncologia - L'Hospitalet ( Site 1805)

L'Hospitalet de Llobregat, Barcelona 08908

Spain

Hospital Universitario Marqués de Valdecilla ( Site 1807)

Santander, Cantabria 39008

Spain

Institut Català d'Oncologia (ICO) - Girona ( Site 1806)

Girona, Gerona 17007

Spain

Hospital Universitario Ramón y Cajal ( Site 1801)

Madrid, Madrid, Comunidad de 28034

Spain

Fundación Instituto Valenciano de Oncología ( Site 1808)

Valencia, Valenciana, Comunitat 46009

Spain

Hospital Universitari Vall d'Hebron ( Site 1804)

Barcelona, 08035

Spain

Hospital Clinic de Barcelona ( Site 1810)

Barcelona, 08036

Spain

Hospital Universitario Reina Sofia ( Site 1809)

Córdoba, 14004

Spain

Hospital Clinico San Carlos ( Site 1802)

Madrid, 28040

Spain

Hospital Universitario Fundacion Jimenez Diaz ( Site 1803)

Madrid, 28040

Spain

Hospital Universitario 12 de Octubre ( Site 1800)

Madrid, 28041

Spain

China Medical University Hospital ( Site 2603)

Taichung, 40447

Taiwan

Taichung Veterans General Hospital ( Site 2602)

Taichung, 40705

Taiwan

Taipei Veterans General Hospital ( Site 2600)

Taipei, 11217

Taiwan

Chang Gung Memorial Hospital - Linkou Branch ( Site 2604)

Taoyuan, 333

Taiwan