RecruitingPhase 3NCT07227402

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

A Phase 3, Randomized, Open-label Study of Belzutifan + Zanzalintinib Versus Cabozantinib in Participants With Advanced RCC Who Experienced Disease Recurrence During or After Prior Adjuvant Anti-PD-1/L1 Therapy (LITESPARK-033)

Sponsor

Merck Sharp & Dohme LLC

Enrollment

904 participants

Start Date

Nov 26, 2025

Study Type

INTERVENTIONAL

Conditions

Renal Cell Carcinoma

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

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This study tests a combination of two targeted drugs — belzutifan and zanzalintinib — in people with advanced kidney cancer (renal cell carcinoma) that came back during or shortly after completing adjuvant immunotherapy (treatment given after surgery to prevent recurrence). **You may be eligible if...** - You have confirmed advanced kidney cancer with clear cell features (stage IV) - Your cancer came back during or within 24 months of completing adjuvant anti-PD-1/L1 immunotherapy - You have received no other systemic treatment for kidney cancer - You have measurable disease on scans **You may NOT be eligible if...** - You have had significant heart problems (heart failure, heart attack, stroke, or serious arrhythmia) within the past 12 months - You had a blood clot in a deep vein within the past 3 months unless stable and treated - Your heart function (ejection fraction) is below 50% - You have had other systemic therapy for your kidney cancer beyond the qualifying adjuvant immunotherapy Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGBelzutifan

Administered orally QD

DRUGZanzalintinib

Administered orally QD

DRUGCabozantinib

Administered orally QD

Locations(105)

Hospital Aleman ( Site 0204)

CABA, Buenos Aires, Argentina

Hospital Italiano de Buenos Aires. ( Site 0203)

Caba, Buenos Aires, Argentina

Asociación de Beneficencia Hospital Sirio Libanés ( Site 0205)

Caba, Buenos Aires, Argentina

Instituto Alexander Fleming ( Site 0202)

CABA, Buenos Aires, Argentina

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

Caba., Buenos Aires F.D., Argentina

Sanatorio Parque ( Site 0201)

Rosario, Santa Fe Province, Argentina

Instituto de Oncología de Rosario ( Site 0209)

Rosario, Santa Fe Province, Argentina

Hospital Privado Universitario de Córdoba ( Site 0207)

Córdoba, Argentina

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

Sydney, New South Wales, Australia

Ordensklinikum Linz GmbH Elisabethinen-Urologie ( Site 0600)

Linz, Upper Austria, Austria

Medizinische Universitat Wien ( Site 0601)

Vienna, Austria

Cliniques Universitaires Saint-Luc ( Site 0703)

Brussels, Bruxelles-Capitale, Region de, Belgium

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

Genk, Limburg, Belgium

UZ Gent ( Site 0702)

Ghent, Oost-Vlaanderen, Belgium

UZ Leuven ( Site 0700)

Leuven, Vlaams-Brabant, Belgium

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

Cuiabá, Mato Grosso, Brazil

Liga Norte Riograndense Contra o Câncer ( Site 0307)

Natal, Rio Grande do Norte, Brazil

Hospital Moinhos de Vento ( Site 0309)

Porto Alegre, Rio Grande do Sul, Brazil

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

São José do Rio Preto, São Paulo, Brazil

Hospital Alemao Oswaldo Cruz ( Site 0311)

São Paulo, São Paulo, Brazil

Masarykuv onkologicky ustav ( Site 0903)

Brno, Brno-mesto, Czechia

Fakultni nemocnice Ostrava ( Site 0904)

Ostrava, Ostrava Mesto, Czechia

Nemocnice České Budějovice ( Site 0905)

České Budějovice, Czechia

Fakultni nemocnice Hradec Kralove ( Site 0902)

Hradec Králové, Czechia

Fakultni nemocnice Olomouc ( Site 0901)

Olomouc, Czechia

Vseobecna fakultni nemocnice v Praze ( Site 0906)

Prague, Czechia

Fakultni nemocnice v Motole ( Site 0900)

Prague, Czechia

Herlev Hospital ( Site 1002)

Herlev, Capital Region, Denmark

Aarhus University Hospital Skejby ( Site 1001)

Aarhus, Central Jutland, Denmark

Odense Universitetshospital ( Site 1000)

Odense, Region Syddanmark, Denmark

CHU de Bordeaux Hop St ANDRE ( Site 1115)

Bordeaux, Gironde, France

Hôpital Foch ( Site 1118)

Suresnes, Hauts-de-Seine, France

Centre de Cancérologie du Grand Montpellier ( Site 1112)

Montpellier, Herault, France

CHU GRENOBLE ALPES ( Site 1101)

La Tronche, Isere, France

Centre d'Oncologie de Gentilly ( Site 1117)

Nancy, Lorraine, France

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

Angers, Pays de la Loire Region, France

Centre Hospitalier de la Côte Basque ( Site 1113)

Bayonne, Pyrenees-Atlantiques, France

centre hospitalier lyon sud ( Site 1102)

Pierre-Bénite, Rhone, France

CHU de Rouen ( Site 1108)

Rouen, Seine-Maritime, France

HENRI MONDOR HOSPITAL ( Site 1116)

Créteil, Val-de-Marne, France

CHD Vendee ( Site 1103)

La Roche-sur-Yon, Vendee, France

Klinikum Stuttgart - Katharinenhospital ( Site 1201)

Stuttgart, Baden-Wurttemberg, Germany

UniversitaetsklInikum Tuebingen ( Site 1207)

Tübingen, Baden-Wurttemberg, Germany

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

Göttingen, Lower Saxony, Germany

Helios Kliniken Schwerin GmbH ( Site 1206)

Schwerin, Mecklenburg-Vorpommern, Germany

Marienhospital Herne ( Site 1215)

Herne, North Rhine-Westphalia, Germany

Universitaetsklinikum Muenster ( Site 1202)

Münster, North Rhine-Westphalia, Germany

Universitaetsklinikum Carl Gustav Carus Dresden ( Site 1213)

Dresden, Saxony, Germany

HELIOS Klinikum Erfurt ( Site 1208)

Erfurt, Thuringia, Germany

Universitätsklinikum Jena ( Site 1204)

Jena, Thuringia, Germany

Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 1203)

Berlin, Germany

Universitaetsklinikum Hamburg-Eppendorf ( Site 1214)

Hamburg, Germany

Alexandra General Hospital of Athens ( Site 1300)

Athens, Attica, Greece

Metropolitan Hospital ( Site 1302)

Athens, Attica, Greece

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

Chaïdári, Attica, 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, Ireland

Tallaght University Hospital ( Site 1500)

Dublin, Ireland

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

Naples, Campania, Italy

Istituto Nazionale Tumori Regina Elena ( Site 1611)

Rome, Lazio, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 1600)

Milan, Milano, Italy

Istituto Clinico Humanitas ( Site 1613)

Rozzano, Milano, Italy

Azienda Ospedaliera S. Luigi Gonzaga ( Site 1607)

Orbassano, Piedmont, Italy

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

Rome, Roma, Italy

Azienda Ospedaliera Universitaria Careggi ( Site 1608)

Florence, Tuscany, Italy

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

Peschiera del Garda, Veneto, Italy

Azienda USL 8 di Arezzo ( Site 1605)

Arezzo, Italy

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

Bologna, Italy

Ospedale San Martino ( Site 1606)

Genova, Italy

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

Guadalajara, Jalisco, Mexico

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

Monterrey, Nuevo León, Mexico

Centro de Investigacion Clinica de Oaxaca ( Site 0502)

Oaxaca City, Oaxaca, Mexico

Higiea Oncologia ( Site 0504)

Mexico City, Mexico

Clinica Integral Internacional de Oncología ( Site 0506)

Puebla City, Mexico

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

Skórzewo, Greater Poland Voivodeship, Poland

Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1707)

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

Pratia MCM Krakow ( Site 1713)

Krakow, Lesser Poland Voivodeship, Poland

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

Krakow, Lesser Poland Voivodeship, Poland

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

Siedlce, Masovian Voivodeship, Poland

MTZ Clinical Research Powered by Pratia ( Site 1705)

Warsaw, Masovian Voivodeship, Poland

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

Przemyśl, Podkarpackie Voivodeship, Poland

National University Hospital ( Site 2400)

Singapore, Central Singapore, Singapore

National Cancer Centre Singapore ( Site 2401)

Singapore, Central Singapore, Singapore

Chonnam National University Hwasun Hospital ( Site 2505)

Hwasun-gun, Jeonranamdo, South Korea

Seoul National University Bundang Hospital ( Site 2504)

Seongnam, Kyonggi-do, South Korea

Chungnam National University Hospital ( Site 2506)

Taejŏn, Taejon-Kwangyokshi, South Korea

Severance Hospital, Yonsei University Health System ( Site 2503)

Seoul, South Korea

Asan Medical Center ( Site 2501)

Seoul, South Korea

Samsung Medical Center ( Site 2502)

Seoul, South Korea

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

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital Universitario Marqués de Valdecilla ( Site 1807)

Santander, Cantabria, Spain

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

Girona, Gerona, Spain

Hospital Universitario Ramón y Cajal ( Site 1801)

Madrid, Madrid, Comunidad de, Spain

Fundación Instituto Valenciano de Oncología ( Site 1808)

Valencia, Valenciana, Comunitat, Spain

Hospital Universitari Vall d'Hebron ( Site 1804)

Barcelona, Spain

Hospital Clinic de Barcelona ( Site 1810)

Barcelona, Spain

Hospital Universitario Reina Sofia ( Site 1809)

Córdoba, Spain

Hospital Clinico San Carlos ( Site 1802)

Madrid, Spain

Hospital Universitario Fundacion Jimenez Diaz ( Site 1803)

Madrid, Spain

Hospital Universitario 12 de Octubre ( Site 1800)

Madrid, Spain

China Medical University Hospital ( Site 2603)

Taichung, Taiwan

Taichung Veterans General Hospital ( Site 2602)

Taichung, Taiwan

Taipei Veterans General Hospital ( Site 2600)

Taipei, Taiwan

Chang Gung Memorial Hospital - Linkou Branch ( Site 2604)

Taoyuan, Taiwan

View Full Details on ClinicalTrials.gov

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