A Clinical Study of Belzutifan (MK-6482) and Zanzalintinib in People With Renal Cell Carcinoma (RCC) (LITESPARK-034/LS-034/MK-6482-034)

NCT07489495 | Recruiting Phase 3 DMC FDA Drug

• 6 other identifiers: 6482-034U1111-1311-46922024-516993-31-00LITESPARK-034MK-6482-034LS-034
• Study Type: interventional
• Target: 758
• Locations: 17 countries
• Sites: 66

Brief Summary

Researchers are looking for new ways to treat advanced renal cell carcinoma (RCC). A standard (usual) treatment for certain people with RCC is belzutifan (a study medicine), which is a targeted therapy. Targeted therapy is a treatment that works to control how specific types of cancer cells grow and spread. Researchers want to learn if adding another targeted therapy called zanzalintinib (another study medicine) can treat more people with advanced RCC than belzutifan alone. The goal of this study is to learn if people who receive belzutifan and zanzalintinib live longer overall and without the cancer getting worse compared to people who receive belzutifan and placebo.

Conditions

Carcinoma, Renal Cell

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival (PFS)

  PFS is defined as the time from randomization to the first documented disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) based on blinded independent central review (BICR) or death due to any cause, whichever occurs first.

  Up to approximately 30 months

• Overall Survival (OS)

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

  Up to approximately 50 months

Secondary Outcomes (12)

• Objective Response Rate (ORR)

  Up to approximately 30 months

• Duration of Response (DOR)

  Up to approximately 30 months

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

  Up to approximately 25 months

• Number of Participants who Discontinue Study Treatment Due to an AE

  Up to approximately 24 months

• Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score

  Baseline and up to approximately 25 months

Study Arms (2)

Belzutifan + Zanzalintinib

EXPERIMENTAL

Participants will receive 120 mg belzutifan orally and 60 mg zanzalintinib once daily for approximately 24 months.

Drug: Belzutifan; Drug: Zanzalintinib

Belzutifan + Placebo

ACTIVE COMPARATOR

Participants will receive 120 mg belzutifan orally and zanzalintinib-matching placebo once daily for approximately 24 months.

Drug: Belzutifan; Drug: Placebo

Interventions

Zanzalintinib DRUG

Tablet for oral administration.

Also known as: XL092

Belzutifan + Zanzalintinib

Placebo DRUG

Zanzalintinib-matching placebo tablet for oral administration.

Belzutifan + Placebo

Belzutifan DRUG

Tablet for oral administration.

Also known as: MK-6482, PT2977, WELIREG

Belzutifan + Placebo; Belzutifan + Zanzalintinib

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 carcinoma (RCC) with clear cell component (with or without sarcomatoid features) ie, Stage IV RCC per American Joint Committee on Cancer (8th Edition)
• Has measurable disease per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)
• Has received no more than 3 prior systemic regimens for RCC, including only 1 prior anti-Programmed Cell Death-1/Programmed Cell Death 1 Ligand 1 therapy

You may not qualify if:

• Has any of the following: a pulse oximeter reading \<92% at rest, requires intermittent supplemental oxygen, or required chronic supplemental oxygen
• Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
• Has 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
• Has current pneumonitis/interstitial lung disease
• Has a history of human immunodeficiency virus infection
• Has Hepatitis B or Hepatitis C virus infection
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has a history of solid organ transplant
• Has not adequately recovered from major surgery or has ongoing surgical complications

Sponsors & Collaborators

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

Study Sites (66)

Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital ( Site 0102)

Marietta, Georgia, 30060, United States

RECRUITING

The West Clinic, P.C. ( Site 0115)

Germantown, Tennessee, 38138, United States

RECRUITING

Centro Oncologico Korben ( Site 0254)

CABA, Buenos Aires, C1426AHB, Argentina

RECRUITING

Hospital Italiano de Buenos Aires ( Site 0253)

Ciudad de Buenos Aires, Buenos Aires, 1181, Argentina

RECRUITING

Instituto de Investigaciones Clinicas Mar del Plata ( Site 0250)

Mar del Plata, Buenos Aires, B7600FZO, Argentina

RECRUITING

Centro Privado de RMI Río Cuarto S.A. II ( Site 0255)

Río Cuarto, Córdoba Province, X5800ALB, Argentina

RECRUITING

Sanatorio Parque ( Site 0251)

Rosario, Santa Fe Province, S2000DSV, Argentina

RECRUITING

Instituto de Oncología de Rosario ( Site 0257)

Rosario, Santa Fe Province, S2000KZE, Argentina

RECRUITING

Instituto Alexander Fleming ( Site 0252)

CABA, C1426ANZ, Argentina

RECRUITING

Centro Oncológico Riojano Integral ( Site 0256)

La Rioja, X5004BAL, Argentina

RECRUITING

COE (Centro Oncológico de Excelencia) ( Site 0259)

San Juan, J5402BGA, Argentina

RECRUITING

Macquarie University ( Site 2700)

Macquarie University, New South Wales, 2109, Australia

SUSPENDED

CEDOES ( Site 0303)

Vitória, Espírito Santo, 29055-450, Brazil

RECRUITING

Instituto do Câncer e Transplante de Curitiba ( Site 0300)

Curitiba, Paraná, 80510-130, Brazil

RECRUITING

Liga Norte Riograndense Contra o Câncer ( Site 0307)

Natal, Rio Grande do Norte, 59062-000, 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

Masarykuv onkologicky ustav ( Site 0903)

Brno, Brno-mesto, 656 53, Czechia

RECRUITING

Fakultni nemocnice Ostrava ( Site 0904)

Ostrava, Ostrava Mesto, 708 52, Czechia

RECRUITING

Fakultni nemocnice Hradec Kralove ( Site 0902)

Hradec Králové, 500 05, Czechia

RECRUITING

Fakultni nemocnice v Motole ( Site 0900)

Prague, 150 06, Czechia

RECRUITING

Herlev Hospital ( Site 1002)

Herlev, Capital Region, 2730, Denmark

RECRUITING

Aarhus Universitetshospital, Skejby ( Site 1001)

Aarhus, Central Jutland, 8200, Denmark

RECRUITING

Centre Antoine Lacassagne ( Site 1209)

Nice, Alpes-Maritimes, 06189, France

RECRUITING

Hopital Europeen Marseille ( Site 1216)

Marseille, Bouches-du-Rhone, 13003, France

RECRUITING

LBM ONCOPOLE CLAUDIUS REGAUD ( Site 1215)

Toulouse, Haute-Garonne, 31059, France

RECRUITING

CHU Angers ( Site 1204)

Angers, Maine-et-Loire, 49933, France

RECRUITING

Clinique Victor Hugo Le Mans-Oncology-Radiotherapy ( Site 1203)

Le Mans, Pays de la Loire Region, 72000, France

RECRUITING

CHU de Saint-Etienne ( Site 1202)

Saint Priest En Jarez, Pays de la Loire Region, 42271, France

RECRUITING

Universitätsklinikum Jena ( Site 1313)

Jena, Thuringia, 07747, Germany

RECRUITING

Alexandra General Hospital of Athens ( Site 1400)

Athens, Attica, 115 28, Greece

RECRUITING

ATTIKON GENERAL UNIVERSITY HOSPITAL ( Site 1401)

Athens, Attica, 124 62, Greece

RECRUITING

Metropolitan Hospital ( Site 1402)

Athens, Attica, 185 47, Greece

RECRUITING

Rambam Health Care Campus ( Site 1600)

Haifa, 3109601, Israel

RECRUITING

Meir Medical Center. ( Site 1603)

Kfar Saba, 4428164, Israel

RECRUITING

Rabin Medical Center ( Site 1602)

Petah Tikva, 4941492, Israel

RECRUITING

Sheba Medical Center ( Site 1601)

Ramat Gan, 5265601, Israel

RECRUITING

IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori" ( Site 1809)

Meldola, Emilia-Romagna, 47014, Italy

RECRUITING

Azienda Ospedaliera Universitaria Careggi ( Site 1807)

Florence, Tuscany, 50134, Italy

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 1800)

Milan, 20133, Italy

RECRUITING

AO Santa Maria della Misericordia ( Site 1805)

Perugia, 06132, Italy

RECRUITING

Istituto Nazionale Tumori Regina Elena ( Site 1804)

Roma, 00144, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore ( Site 1801)

Roma, 00168, Italy

RECRUITING

Maastricht UMC+ ( Site 1901)

Maastricht, Limburg, 6229 HX, Netherlands

RECRUITING

Nederlands Kanker Instituut Antoni van Leeuwenhoek (NKI AVL) ( Site 1900)

Amsterdam, North Holland, 1066 CX, Netherlands

RECRUITING

Haga Ziekenhuis locatie Leyweg ( Site 1906)

The Hague, South Holland, 2545 AA, Netherlands

RECRUITING

AIDPORT Sp. z o.o. ( Site 2118)

Skórzewo, Greater Poland Voivodeship, 60-185, Poland

RECRUITING

Pratia MCM Krakow ( Site 2115)

Krakow, Lesser Poland Voivodeship, 30-727, Poland

RECRUITING

Mazowiecki Szpital Wojewódzki w Siedlcach-Siedleckie Centrum Onkologii ( Site 2102)

Siedlce, Masovian Voivodeship, 08-110, Poland

RECRUITING

MTZ Clinical Research Powered by Pratia ( Site 2107)

Warsaw, Masovian Voivodeship, 02-172, Poland

RECRUITING

Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 2106)

Gliwice, Silesian Voivodeship, 44-102, Poland

RECRUITING

Severance Hospital, Yonsei University Health System ( Site 2903)

Seoul, 03722, South Korea

RECRUITING

Asan Medical Center ( Site 2901)

Seoul, 05505, South Korea

RECRUITING

Samsung Medical Center ( Site 2902)

Seoul, 06351, South Korea

RECRUITING

Hospital Universitario Virgen del Rocio ( Site 2306)

Seville, Andalusia, 41013, Spain

RECRUITING

Institut Català d'Oncologia - L'Hospitalet ( Site 2305)

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

RECRUITING

HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 2301)

Madrid, Madrid, Comunidad de, 28007, Spain

RECRUITING

Hospital Universitari Vall d'Hebron ( Site 2303)

Barcelona, 08035, Spain

RECRUITING

Hospital Insular de Gran Canaria ( Site 2308)

Las Palmas, 35016, Spain

RECRUITING

Hospital Universitario 12 de Octubre ( Site 2300)

Madrid, 28041, Spain

RECRUITING

Fundación Instituto Valenciano de Oncología ( Site 2307)

Valencia, 46009, Spain

RECRUITING

Hacettepe Universite Hastaneleri ( Site 2500)

Sıhhiye, Ankara, 06230, Turkey (Türkiye)

RECRUITING

Adana Medical Park Seyhan Hastanesi ( Site 2505)

Adana, 01140, Turkey (Türkiye)

RECRUITING

Ankara University Health Practice and Research Hospitals ( Site 2506)

Ankara, 06620, Turkey (Türkiye)

RECRUITING

Trakya University Medical Faculty Hospital ( Site 2502)

Edirne, 22030, Turkey (Türkiye)

RECRUITING

Koc Universitesi Hastanesi ( Site 2501)

Istanbul, 34010, Turkey (Türkiye)

RECRUITING

The Christie Hospital NHS Foundation Trust ( Site 2601)

Withington, Manchester, M20 4BX, United Kingdom

RECRUITING

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

belzutifan

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; 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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2026
• First Posted: March 24, 2026
• Study Start: April 9, 2026
• Primary Completion (Estimated): November 27, 2030
• Study Completion (Estimated): November 27, 2030
• Last Updated: July 27, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share

Locations

US (2); AR (9); PL (5); CZ (4); KR (3); AU (1); IL (4); GR (3); ES (7); DK (2); NL (3); FR (6); IT (6); TU (5); BR (4); GB (1); DE (1)