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

NCT07227402 | Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: 6482-033U1111-1311-68922024-517136-21
• Study Type: interventional
• Target: 904
• Locations: 18 countries
• Sites: 104

Brief 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.

Conditions

Renal Cell Carcinoma

Keywords

Carcinoma; Renal cell; Belzutifan; Zanzalintinib

Outcome Measures

Primary Outcomes (2)

• Progression Free Survival (PFS)

  PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. PD will be assessed by Response Criteria in Solid Tumors Version 1.1 (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 (BICR) will be presented.

  Up to approximately 73 months

• Overall Survival (OS)

  OS is defined as the time from randomization to death due to any cause.

  Up to approximately 73 months

Secondary Outcomes (12)

• Objective Response Rate (ORR)

  Up to approximately 73 months

• Duration of Response (DOR)

  Up to approximately 73 months

• Number of Participants Who Experience One or More Adverse Events (AEs)

  Up to approximately 73 months

• Number of Participants Who Discontinue Study Treatment due to an AE

  Up to approximately 73 months

• Change From Baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) Global Health/Health-Related Quality of Life (HRQoL) Items 29 and 30 Combined Score

  Up to approximately 25 months

Study Arms (2)

Belzutifan plus Zanzalintinib

EXPERIMENTAL

Participants will receive belzutifan orally once daily (QD) PLUS zanzalintinib orally QD until one of the reasons for discontinuation of study intervention are met.

Drug: Belzutifan; Drug: Zanzalintinib

Cabozantinib

ACTIVE COMPARATOR

Participants will receive cabozantinib orally QD until one of the reasons for discontinuation of study intervention are met.

Drug: Cabozantinib

Interventions

Belzutifan DRUG

Administered orally QD

Also known as: MK-6482, PT2977, WELIREG™

Belzutifan plus Zanzalintinib

Zanzalintinib DRUG

Administered orally QD

Also known as: XL092

Belzutifan plus Zanzalintinib

Cabozantinib DRUG

Administered orally QD

Cabozantinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention

Sponsors & Collaborators

• Exelixis: collaborator
• Merck Sharp & Dohme LLC: lead

Study Sites (105)

Hospital Aleman ( Site 0204)

CABA, Buenos Aires, C1118AAT, Argentina

RECRUITING

Hospital Italiano de Buenos Aires. ( Site 0203)

Caba, Buenos Aires, C1199ABB, Argentina

RECRUITING

Asociación de Beneficencia Hospital Sirio Libanés ( Site 0205)

Caba, Buenos Aires, C1419AHN, Argentina

RECRUITING

Instituto Alexander Fleming ( Site 0202)

CABA, Buenos Aires, C1426ANZ, Argentina

RECRUITING

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

Caba., Buenos Aires F.D., C1431FWO, Argentina

RECRUITING

Sanatorio Parque ( Site 0201)

Rosario, Santa Fe Province, S2000DSV, Argentina

RECRUITING

Instituto de Oncología de Rosario ( Site 0209)

Rosario, Santa Fe Province, S2000KZE, Argentina

RECRUITING

Hospital Privado Universitario de Córdoba ( Site 0207)

Córdoba, X5016KEH, Argentina

RECRUITING

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

Sydney, New South Wales, 2109, Australia

RECRUITING

Ordensklinikum Linz GmbH Elisabethinen-Urologie ( Site 0600)

Linz, Upper Austria, 4020, Austria

RECRUITING

Medizinische Universitat Wien ( Site 0601)

Vienna, 1090, Austria

RECRUITING

Cliniques Universitaires Saint-Luc ( Site 0703)

Brussels, Bruxelles-Capitale, Region de, 1200, Belgium

RECRUITING

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

Genk, Limburg, 3600, Belgium

RECRUITING

UZ Gent ( Site 0702)

Ghent, Oost-Vlaanderen, 9000, Belgium

RECRUITING

UZ Leuven ( Site 0700)

Leuven, Vlaams-Brabant, 3000, Belgium

RECRUITING

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

Cuiabá, Mato Grosso, 78020-500, Brazil

RECRUITING

Liga Norte Riograndense Contra o Câncer ( Site 0307)

Natal, Rio Grande do Norte, 59062-000, Brazil

RECRUITING

Hospital Moinhos de Vento ( Site 0309)

Porto Alegre, Rio Grande do Sul, 90560-032, Brazil

RECRUITING

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

São José do Rio Preto, São Paulo, 15090-000, Brazil

RECRUITING

Hospital Alemao Oswaldo Cruz ( Site 0311)

São Paulo, São Paulo, 01327-001, Brazil

RECRUITING

Masarykuv onkologicky ustav ( Site 0903)

Brno, Brno-mesto, 656 53, Czechia

RECRUITING

Fakultni nemocnice Ostrava ( Site 0904)

Ostrava, Ostrava Mesto, 708 52, Czechia

RECRUITING

Nemocnice České Budějovice ( Site 0905)

České Budějovice, 370 01, Czechia

RECRUITING

Fakultni nemocnice Hradec Kralove ( Site 0902)

Hradec Králové, 500 05, Czechia

RECRUITING

Fakultni nemocnice Olomouc ( Site 0901)

Olomouc, 779 00, Czechia

RECRUITING

Vseobecna fakultni nemocnice v Praze ( Site 0906)

Prague, 128 08, Czechia

RECRUITING

Fakultni nemocnice v Motole ( Site 0900)

Prague, 150 06, Czechia

RECRUITING

Herlev Hospital ( Site 1002)

Herlev, Capital Region, 2730, Denmark

RECRUITING

Aarhus University Hospital Skejby ( Site 1001)

Aarhus, Central Jutland, 8200, Denmark

RECRUITING

Odense Universitetshospital ( Site 1000)

Odense, Region Syddanmark, 9000, Denmark

RECRUITING

CHU de Bordeaux Hop St ANDRE ( Site 1115)

Bordeaux, Gironde, 33075, France

RECRUITING

Hôpital Foch ( Site 1118)

Suresnes, Hauts-de-Seine, 92150, France

RECRUITING

Centre de Cancérologie du Grand Montpellier ( Site 1112)

Montpellier, Herault, 34070, France

RECRUITING

CHU GRENOBLE ALPES ( Site 1101)

La Tronche, Isere, 38700, France

RECRUITING

Centre d'Oncologie de Gentilly ( Site 1117)

Nancy, Lorraine, 54100, France

RECRUITING

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

Angers, Pays de la Loire Region, 49933, France

RECRUITING

Centre Hospitalier de la Côte Basque ( Site 1113)

Bayonne, Pyrenees-Atlantiques, 64109, France

RECRUITING

centre hospitalier lyon sud ( Site 1102)

Pierre-Bénite, Rhone, 69310, France

RECRUITING

CHU de Rouen ( Site 1108)

Rouen, Seine-Maritime, 76031, France

RECRUITING

HENRI MONDOR HOSPITAL ( Site 1116)

Créteil, Val-de-Marne, 94010, France

RECRUITING

CHD Vendee ( Site 1103)

La Roche-sur-Yon, Vendee, 85000, France

RECRUITING

Klinikum Stuttgart - Katharinenhospital ( Site 1201)

Stuttgart, Baden-Wurttemberg, 70174, Germany

RECRUITING

UniversitaetsklInikum Tuebingen ( Site 1207)

Tübingen, Baden-Wurttemberg, 72076, Germany

RECRUITING

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

Göttingen, Lower Saxony, 37075, Germany

RECRUITING

Helios Kliniken Schwerin GmbH ( Site 1206)

Schwerin, Mecklenburg-Vorpommern, 19055, Germany

RECRUITING

Marienhospital Herne ( Site 1215)

Herne, North Rhine-Westphalia, 44625, Germany

RECRUITING

Universitaetsklinikum Muenster ( Site 1202)

Münster, North Rhine-Westphalia, 70174, Germany

RECRUITING

Universitaetsklinikum Carl Gustav Carus Dresden ( Site 1213)

Dresden, Saxony, 01307, Germany

RECRUITING

HELIOS Klinikum Erfurt ( Site 1208)

Erfurt, Thuringia, 99089, Germany

RECRUITING

Universitätsklinikum Jena ( Site 1204)

Jena, Thuringia, 07747, Germany

RECRUITING

Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 1203)

Berlin, 10117, Germany

RECRUITING

Universitaetsklinikum Hamburg-Eppendorf ( Site 1214)

Hamburg, 20246, Germany

RECRUITING

Alexandra General Hospital of Athens ( Site 1300)

Athens, Attica, 115 28, Greece

RECRUITING

Metropolitan Hospital ( Site 1302)

Athens, Attica, 185 47, Greece

RECRUITING

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

Chaïdári, Attica, 124 62, Greece

RECRUITING

Prince of Wales Hospital ( Site 2200)

Hong Kong, Hong Kong

RECRUITING

Queen Mary Hospital ( Site 2201)

Hong Kong, Hong Kong

RECRUITING

Cork University Hospital ( Site 1501)

Cork, T12 YK23, Ireland

RECRUITING

Tallaght University Hospital ( Site 1500)

Dublin, D24 NR0A, Ireland

RECRUITING

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

Naples, Campania, 80131, Italy

RECRUITING

Istituto Nazionale Tumori Regina Elena ( Site 1611)

Rome, Lazio, 00144, Italy

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 1600)

Milan, Milano, 20133, Italy

RECRUITING

Istituto Clinico Humanitas ( Site 1613)

Rozzano, Milano, 20089, Italy

RECRUITING

Azienda Ospedaliera S. Luigi Gonzaga ( Site 1607)

Orbassano, Piedmont, 10043, Italy

RECRUITING

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

Rome, Roma, 00618, Italy

RECRUITING

Azienda Ospedaliera Universitaria Careggi ( Site 1608)

Florence, Tuscany, 50134, Italy

RECRUITING

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

Peschiera del Garda, Veneto, 37019, Italy

RECRUITING

Azienda USL 8 di Arezzo ( Site 1605)

Arezzo, 52100, Italy

RECRUITING

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

Bologna, 40138, Italy

RECRUITING

Ospedale San Martino ( Site 1606)

Genova, 16132, Italy

RECRUITING

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

Guadalajara, Jalisco, 44630, Mexico

RECRUITING

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

Monterrey, Nuevo León, 64710, Mexico

RECRUITING

Centro de Investigacion Clinica de Oaxaca ( Site 0502)

Oaxaca City, Oaxaca, 68020, Mexico

RECRUITING

Higiea Oncologia ( Site 0504)

Mexico City, 11810, Mexico

RECRUITING

Clinica Integral Internacional de Oncología ( Site 0506)

Puebla City, 72530, Mexico

RECRUITING

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

Skórzewo, Greater Poland Voivodeship, 60-185, Poland

RECRUITING

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

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-796, Poland

RECRUITING

Pratia MCM Krakow ( Site 1713)

Krakow, Lesser Poland Voivodeship, 30-727, Poland

RECRUITING

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

Krakow, Lesser Poland Voivodeship, 31-826, Poland

RECRUITING

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

Siedlce, Masovian Voivodeship, 08-110, Poland

RECRUITING

MTZ Clinical Research Powered by Pratia ( Site 1705)

Warsaw, Masovian Voivodeship, 02-172, Poland

RECRUITING

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

Przemyśl, Podkarpackie Voivodeship, 37-700, Poland

RECRUITING

National University Hospital ( Site 2400)

Singapore, Central Singapore, 119074, Singapore

RECRUITING

National Cancer Centre Singapore ( Site 2401)

Singapore, Central Singapore, 168583, Singapore

RECRUITING

Chonnam National University Hwasun Hospital ( Site 2505)

Hwasun-gun, Jeonranamdo, 58128, South Korea

RECRUITING

Seoul National University Bundang Hospital ( Site 2504)

Seongnam, Kyonggi-do, 13620, South Korea

RECRUITING

Chungnam National University Hospital ( Site 2506)

Taejŏn, Taejon-Kwangyokshi, 35015, South Korea

RECRUITING

Severance Hospital, Yonsei University Health System ( Site 2503)

Seoul, 03722, South Korea

RECRUITING

Asan Medical Center ( Site 2501)

Seoul, 05505, South Korea

RECRUITING

Samsung Medical Center ( Site 2502)

Seoul, 06351, South Korea

RECRUITING

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

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

RECRUITING

Hospital Universitario Marqués de Valdecilla ( Site 1807)

Santander, Cantabria, 39008, Spain

RECRUITING

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

Girona, Gerona, 17007, Spain

RECRUITING

Hospital Universitario Ramón y Cajal ( Site 1801)

Madrid, Madrid, Comunidad de, 28034, Spain

RECRUITING

Fundación Instituto Valenciano de Oncología ( Site 1808)

Valencia, Valenciana, Comunitat, 46009, Spain

RECRUITING

Hospital Universitari Vall d'Hebron ( Site 1804)

Barcelona, 08035, Spain

RECRUITING

Hospital Clinic de Barcelona ( Site 1810)

Barcelona, 08036, Spain

RECRUITING

Hospital Universitario Reina Sofia ( Site 1809)

Córdoba, 14004, Spain

RECRUITING

Hospital Clinico San Carlos ( Site 1802)

Madrid, 28040, Spain

RECRUITING

Hospital Universitario Fundacion Jimenez Diaz ( Site 1803)

Madrid, 28040, Spain

RECRUITING

Hospital Universitario 12 de Octubre ( Site 1800)

Madrid, 28041, Spain

RECRUITING

China Medical University Hospital ( Site 2603)

Taichung, 40447, Taiwan

RECRUITING

Taichung Veterans General Hospital ( Site 2602)

Taichung, 40705, Taiwan

RECRUITING

Taipei Veterans General Hospital ( Site 2600)

Taipei, 11217, Taiwan

RECRUITING

Chang Gung Memorial Hospital - Linkou Branch ( Site 2604)

Taoyuan, 333, Taiwan

RECRUITING

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Carcinoma, Renal Cell; Carcinoma

Interventions

belzutifan; cabozantinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Central Study Contacts

Toll Free Number

CONTACT

1-888-577-8839; Trialsites@msd.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2025
• First Posted: November 12, 2025
• Study Start: November 26, 2025
• Primary Completion (Estimated): February 27, 2032
• Study Completion (Estimated): February 27, 2032
• Last Updated: May 4, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

BE (4); HK (2); PL (7); IE (2); SG (2); DE (11); DK (3); FR (11); TW (4); CZ (7); IT (11); ME (5); AR (8); KR (6); ES (11); GR (3); AU (2); BR (5)