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

September 15, 2026 updated by: Merck Sharp & Dohme LLC

A Phase 3, Randomized, Double-blind, Study of Belzutifan + Zanzalintinib Versus Belzutifan + Placebo in Participants With Advanced RCC Who Have Progressed on or After Both PD-1/L1 and VEGF-TKI Therapies in Sequence or in Combination (LITESPARK-034)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

758

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Argentina
      • CABA, Argentina, C1426ANZ
        • Recruiting
        • Instituto Alexander Fleming ( Site 0252)
        • Contact:
          • Study Coordinator
          • Phone Number: +541132218900
      • La Rioja, Argentina, X5004BAL
        • Recruiting
        • Centro Oncológico Riojano Integral ( Site 0256)
        • Contact:
          • Study Coordinator
          • Phone Number: +543804436443X108
      • San Juan, Argentina, J5402BGA
        • Recruiting
        • COE (Centro Oncológico de Excelencia) ( Site 0259)
        • Contact:
          • Study Coordinator
          • Phone Number: +54 2644229585
    • Buenos Aires
      • CABA, Buenos Aires, Argentina, C1426AHB
        • Recruiting
        • Centro Oncologico Korben ( Site 0254)
        • Contact:
          • Study Coordinator
          • Phone Number: +541159507952
      • Ciudad de Buenos Aires, Buenos Aires, Argentina, 1181
        • Recruiting
        • Hospital Italiano de Buenos Aires ( Site 0253)
        • Contact:
          • Study Coordinator
          • Phone Number: +541149590200
      • Mar del Plata, Buenos Aires, Argentina, B7600FZO
        • Recruiting
        • Instituto de Investigaciones Clinicas Mar del Plata ( Site 0250)
        • Contact:
          • Study Coordinator
          • Phone Number: +542234963224
    • Córdoba Province
      • Río Cuarto, Córdoba Province, Argentina, X5800ALB
        • Recruiting
        • Centro Privado de RMI Río Cuarto S.A. II ( Site 0255)
        • Contact:
          • Study Coordinator
          • Phone Number: +543584620273
    • Santa Fe Province
      • Rosario, Santa Fe Province, Argentina, S2000DSV
        • Recruiting
        • Sanatorio Parque ( Site 0251)
        • Contact:
          • Study Coordinator
          • Phone Number: +5493416955611
      • Rosario, Santa Fe Province, Argentina, S2000KZE
        • Recruiting
        • Instituto de Oncología de Rosario ( Site 0257)
        • Contact:
          • Study Coordinator
          • Phone Number: +543414484830
  • Australia
    • New South Wales
      • Macquarie University, New South Wales, Australia, 2109
        • Suspended
        • Macquarie University ( Site 2700)
    • Queensland
      • Woolloongabba, Queensland, Australia, 4102
        • Suspended
        • Princess Alexandra Hospital ( Site 2703)
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • Suspended
        • Peter MacCallum Cancer Centre ( Site 2702)
  • Brazil
    • Espírito Santo
      • Vitória, Espírito Santo, Brazil, 29055-450
        • Recruiting
        • CEDOES ( Site 0303)
        • Contact:
          • Study Coordinator
          • Phone Number: +552721250202
    • Paraná
      • Curitiba, Paraná, Brazil, 80510-130
        • Recruiting
        • Instituto do Câncer e Transplante de Curitiba ( Site 0300)
        • Contact:
          • Study Coordinator
          • Phone Number: +55 41 99205-7755
    • Rio Grande do Norte
      • Natal, Rio Grande do Norte, Brazil, 59062-000
        • Recruiting
        • Liga Norte Riograndense Contra o Câncer ( Site 0307)
        • Contact:
          • Study Coordinator
          • Phone Number: +55 84 4009-5595
    • São Paulo
      • Ribeirão Preto, São Paulo, Brazil, 14026-610
        • Recruiting
        • Hope - Humanizacao Em Oncologia, Pesquisa E Ensino ( Site 0306)
        • Contact:
          • Study Coordinator
          • Phone Number: +55 16 3913-8181
      • São José do Rio Preto, São Paulo, Brazil, 15090-000
        • Recruiting
        • Fundação Faculdade Regional de Medicina de São José do Rio Preto ( Site 0302)
        • Contact:
          • Study Coordinator
          • Phone Number: +55 17 3201-5054
  • Canada
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • Recruiting
        • The Ottawa Hospital Cancer Centre ( Site 0003)
        • Contact:
          • Study Coordinator
          • Phone Number: 613-737-7700
  • Chile
    • Coquimbo Region
      • La Serena, Coquimbo Region, Chile, 1720430
        • Recruiting
        • IC La Serena Research ( Site 0405)
        • Contact:
          • Study Coordinator
          • Phone Number: 56958646664
    • Los Lagos Region
      • Port Montt, Los Lagos Region, Chile, 5500243
        • Recruiting
        • Clínica Puerto Montt ( Site 0404)
        • Contact:
          • Study Coordinator
          • Phone Number: +56985383586
    • Region M. de Santiago
      • Santiago, Region M. de Santiago, Chile, 7500921
        • Recruiting
        • Fundacion Arturo Lopez Perez ( Site 0401)
        • Contact:
          • Study Coordinator
          • Phone Number: 56224205098
      • Santiago, Region M. de Santiago, Chile, 8420383
        • Recruiting
        • Bradfordhill ( Site 0400)
        • Contact:
          • Study Coordinator
          • Phone Number: 56229490970
    • Valparaiso
      • Viña del Mar, Valparaiso, Chile, 2520598
        • Recruiting
        • ONCOCENTRO APYS ( Site 0403)
        • Contact:
          • Study Coordinator
          • Phone Number: 56323320850
  • Czechia
      • Hradec Králové, Czechia, 500 05
        • Recruiting
        • Fakultni nemocnice Hradec Kralove ( Site 0902)
        • Contact:
          • Study Coordinator
          • Phone Number: +420727854666
      • Olomouc, Czechia, 779 00
        • Recruiting
        • Fakultni nemocnice Olomouc ( Site 0901)
        • Contact:
          • Study Coordinator
          • Phone Number: +420588445923
      • Prague, Czechia, 150 06
        • Recruiting
        • Fakultni nemocnice v Motole ( Site 0900)
        • Contact:
          • Study Coordinator
          • Phone Number: +420734236410
      • Prague, Czechia, 128 08
        • Recruiting
        • Fakulti poliklinika ( Site 0906)
        • Contact:
          • Study Coordinator
          • Phone Number: +420224966405
    • Brno-mesto
      • Brno, Brno-mesto, Czechia, 656 53
        • Recruiting
        • Masarykuv onkologicky ustav ( Site 0903)
        • Contact:
          • Study Coordinator
          • Phone Number: +420543132216
    • Ostrava Mesto
      • Ostrava, Ostrava Mesto, Czechia, 708 52
        • Recruiting
        • Fakultni nemocnice Ostrava ( Site 0904)
        • Contact:
          • Study Coordinator
          • Phone Number: +420597374322
  • Denmark
    • Capital Region
      • Herlev, Capital Region, Denmark, 2730
        • Recruiting
        • Herlev Hospital ( Site 1002)
        • Contact:
          • Study Coordinator
          • Phone Number: 00 45 38689191
    • Central Jutland
      • Aarhus, Central Jutland, Denmark, 8200
        • Recruiting
        • Aarhus Universitetshospital, Skejby ( Site 1001)
        • Contact:
          • Study Coordinator
          • Phone Number: +4591167472
  • France
    • Alpes-Maritimes
      • Nice, Alpes-Maritimes, France, 06189
        • Recruiting
        • Centre Antoine Lacassagne ( Site 1209)
        • Contact:
          • Study Coordinator
          • Phone Number: +33492031538
    • Bouches-du-Rhone
      • Marseille, Bouches-du-Rhone, France, 13003
        • Recruiting
        • Hopital Europeen Marseille ( Site 1216)
        • Contact:
          • Study Coordinator
          • Phone Number: +33413427427
    • Haute-Garonne
      • Toulouse, Haute-Garonne, France, 31059
        • Recruiting
        • LBM ONCOPOLE CLAUDIUS REGAUD ( Site 1215)
        • Contact:
          • Study Coordinator
          • Phone Number: +33531155050
    • Maine-et-Loire
      • Angers, Maine-et-Loire, France, 49933
        • Recruiting
        • CHU Angers ( Site 1204)
        • Contact:
          • Study Coordinator
          • Phone Number: +33241354694
    • Pays de la Loire Region
      • Le Mans, Pays de la Loire Region, France, 72000
        • Recruiting
        • Clinique Victor Hugo Le Mans-Oncology-Radiotherapy ( Site 1203)
        • Contact:
          • Study Coordinator
          • Phone Number: +33 243297908
      • Saint Priest En Jarez, Pays de la Loire Region, France, 42271
        • Recruiting
        • CHU de Saint-Etienne ( Site 1202)
        • Contact:
          • Study Coordinator
          • Phone Number: +33477917082
  • Germany
      • Berlin, Germany, 10117
        • Recruiting
        • Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 1312)
        • Contact:
          • Study Coordinator
          • Phone Number: +4930450515288
    • Bavaria
      • Augsburg, Bavaria, Germany, 86156
        • Recruiting
        • Universitaetsklinikum Augsburg ( Site 1316)
        • Contact:
          • Study Coordinator
          • Phone Number: +498214002348
      • Munich, Bavaria, Germany, 81675
        • Recruiting
        • klinikum rechts der isar der technischen universität münchen ( Site 1315)
        • Contact:
          • Study Coordinator
          • Phone Number: 00498941402522
    • Thuringia
      • Jena, Thuringia, Germany, 07747
        • Recruiting
        • Universitätsklinikum Jena ( Site 1313)
        • Contact:
          • Study Coordinator
          • Phone Number: +4936419329970
  • Greece
    • Attica
      • Athens, Attica, Greece, 185 47
        • Recruiting
        • Metropolitan Hospital ( Site 1402)
        • Contact:
          • Study Coordinator
          • Phone Number: +302104809667
      • Athens, Attica, Greece, 124 62
        • Recruiting
        • ATTIKON GENERAL UNIVERSITY HOSPITAL ( Site 1401)
        • Contact:
          • Study Coordinator
          • Phone Number: +302105832549
      • Athens, Attica, Greece, 115 28
        • Recruiting
        • Alexandra General Hospital of Athens ( Site 1400)
        • Contact:
          • Study Coordinator
          • Phone Number: +302132162543
  • Israel
      • Haifa, Israel, 3109601
        • Recruiting
        • Rambam Health Care Campus ( Site 1600)
        • Contact:
          • Study Coordinator
          • Phone Number: +97247772688
      • Kfar Saba, Israel, 4428164
        • Recruiting
        • Meir Medical Center. ( Site 1603)
        • Contact:
          • Study Coordinator
          • Phone Number: +97297472555
      • Petah Tikva, Israel, 4941492
        • Recruiting
        • Rabin Medical Center ( Site 1602)
        • Contact:
          • Study Coordinator
          • Phone Number: 97239378074
      • Ramat Gan, Israel, 5265601
        • Recruiting
        • Sheba Medical Center ( Site 1601)
        • Contact:
          • Study Coordinator
          • Phone Number: 97235303030
  • Italy
      • Bari, Italy, 70124
        • Recruiting
        • A.O.U.C. Policlinico di Bari ( Site 1802)
        • Contact:
          • Study Coordinator
          • Phone Number: 00390805593767
      • Bologna, Italy, 40138
        • Recruiting
        • IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola ( Site 1803)
        • Contact:
          • Study Coordinator
          • Phone Number: +390512142204
      • Milan, Italy, 20133
        • Recruiting
        • Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 1800)
        • Contact:
          • Study Coordinator
          • Phone Number: 02 2390 3028
      • Perugia, Italy, 06132
        • Recruiting
        • AO Santa Maria della Misericordia ( Site 1805)
        • Contact:
          • Study Coordinator
          • Phone Number: +39 0755784188
      • Roma, Italy, 00168
        • Recruiting
        • Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore ( Site 1801)
        • Contact:
          • Study Coordinator
          • Phone Number: 00390630155202
      • Roma, Italy, 00144
        • Recruiting
        • Istituto Nazionale Tumori Regina Elena ( Site 1804)
        • Contact:
          • Study Coordinator
          • Phone Number: +39 0652666919
    • Emilia-Romagna
      • Meldola, Emilia-Romagna, Italy, 47014
        • Recruiting
        • IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori" ( Site 1809)
        • Contact:
          • Study Coordinator
          • Phone Number: +390543739100
    • Milano
      • Rozzano, Milano, Italy, 20089
        • Recruiting
        • Istituto Clinico Humanitas ( Site 1808)
        • Contact:
          • Study Coordinator
          • Phone Number: 0282244061
    • Padova
      • Catselfranco Veneto, Padova, Italy, 31033
        • Recruiting
        • Istituto Oncologico Veneto IRCCS ( Site 1806)
        • Contact:
          • Study Coordinator
          • Phone Number: +39 0423732336
    • Tuscany
      • Florence, Tuscany, Italy, 50134
        • Recruiting
        • Azienda Ospedaliera Universitaria Careggi ( Site 1807)
        • Contact:
          • Study Coordinator
          • Phone Number: +390557949648
  • Netherlands
    • Limburg
      • Maastricht, Limburg, Netherlands, 6229 HX
        • Recruiting
        • Maastricht UMC+ ( Site 1901)
        • Contact:
          • Study Coordinator
          • Phone Number: +31433877025
    • North Holland
      • Amsterdam, North Holland, Netherlands, 1066 CX
        • Recruiting
        • Nederlands Kanker Instituut Antoni van Leeuwenhoek (NKI AVL) ( Site 1900)
        • Contact:
          • Study Coordinator
          • Phone Number: +3120 512 9111
    • South Holland
      • The Hague, South Holland, Netherlands, 2545 AA
        • Recruiting
        • Haga Ziekenhuis locatie Leyweg ( Site 1906)
        • Contact:
          • Study Coordinator
          • Phone Number: +3170 210 2143
  • Poland
    • Greater Poland Voivodeship
      • Skórzewo, Greater Poland Voivodeship, Poland, 60-185
        • Recruiting
        • AIDPORT Sp. z o.o. ( Site 2118)
        • Contact:
          • Study Coordinator
          • Phone Number: +48570783100
    • Lesser Poland Voivodeship
      • Krakow, Lesser Poland Voivodeship, Poland, 30-727
        • Recruiting
        • Pratia MCM Krakow ( Site 2115)
        • Contact:
          • Study Coordinator
          • Phone Number: +48122958160
    • Masovian Voivodeship
      • Siedlce, Masovian Voivodeship, Poland, 08-110
        • Recruiting
        • Mazowiecki Szpital Wojewódzki w Siedlcach-Siedleckie Centrum Onkologii ( Site 2102)
        • Contact:
          • Study Coordinator
          • Phone Number: +48256403300
      • Warsaw, Masovian Voivodeship, Poland, 02-172
        • Recruiting
        • MTZ Clinical Research Powered by Pratia ( Site 2107)
        • Contact:
          • Study Coordinator
          • Phone Number: +48225725959
      • Warsaw, Masovian Voivodeship, Poland, 02-781
        • Recruiting
        • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Układu Moczowego ( Site 2100)
        • Contact:
          • Study Coordinator
          • Phone Number: +48225462331
    • Silesian Voivodeship
      • Gliwice, Silesian Voivodeship, Poland, 44-102
        • Recruiting
        • Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 2106)
        • Contact:
          • Study Coordinator
          • Phone Number: +48322788237
  • South Korea
      • Seoul, South Korea, 05505
        • Recruiting
        • Asan Medical Center ( Site 2901)
        • Contact:
          • Study Coordinator
          • Phone Number: +82-2-3010-5977
      • Seoul, South Korea, 06351
        • Recruiting
        • Samsung Medical Center ( Site 2902)
        • Contact:
          • Study Coordinator
          • Phone Number: +82-2-3410-1767
      • Seoul, South Korea, 03722
        • Recruiting
        • Severance Hospital, Yonsei University Health System ( Site 2903)
        • Contact:
          • Study Coordinator
          • Phone Number: +82-2-2228-8138
  • Spain
      • Barcelona, Spain, 08035
        • Recruiting
        • Hospital Universitari Vall d'Hebron ( Site 2303)
        • Contact:
          • Study Coordinator
          • Phone Number: +34934894350
      • Las Palmas, Spain, 35016
        • Recruiting
        • Hospital Insular de Gran Canaria ( Site 2308)
        • Contact:
          • Study Coordinator
          • Phone Number: +34928441738
      • Madrid, Spain, 28041
        • Recruiting
        • Hospital Universitario 12 de Octubre ( Site 2300)
        • Contact:
          • Study Coordinator
          • Phone Number: +34913908339
      • Valencia, Spain, 46009
        • Recruiting
        • Fundación Instituto Valenciano de Oncología ( Site 2307)
        • Contact:
          • Study Coordinator
          • Phone Number: +34961114229
    • Andalusia
      • Seville, Andalusia, Spain, 41013
        • Recruiting
        • Hospital Universitario Virgen del Rocio ( Site 2306)
        • Contact:
          • Study Coordinator
          • Phone Number: +34955013068
    • Barcelona
      • L'Hospitalet de Llobregat, Barcelona, Spain, 08908
        • Recruiting
        • Institut Català d'Oncologia - L'Hospitalet ( Site 2305)
        • Contact:
          • Study Coordinator
          • Phone Number: +34932607744
    • Madrid, Comunidad de
      • Madrid, Madrid, Comunidad de, Spain, 28007
        • Recruiting
        • HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 2301)
        • Contact:
          • Study Coordinator
          • Phone Number: +34914269393
  • Turkey (Türkiye)
      • Adana, Turkey (Türkiye), 01140
        • Recruiting
        • Adana Medical Park Seyhan Hastanesi ( Site 2505)
        • Contact:
          • Study Coordinator
          • Phone Number: +905372688986
      • Ankara, Turkey (Türkiye), 06620
        • Recruiting
        • Ankara University Health Practice and Research Hospitals ( Site 2506)
        • Contact:
          • Study Coordinator
          • Phone Number: +90 312 595 71 12
      • Edirne, Turkey (Türkiye), 22030
        • Recruiting
        • Trakya University Medical Faculty Hospital ( Site 2502)
        • Contact:
          • Study Coordinator
          • Phone Number: +9005378528123
      • Istanbul, Turkey (Türkiye), 34010
        • Recruiting
        • Koc Universitesi Hastanesi ( Site 2501)
        • Contact:
          • Study Coordinator
          • Phone Number: 0090 850 250 8 250
    • Ankara
      • Sıhhiye, Ankara, Turkey (Türkiye), 06230
        • Recruiting
        • Hacettepe Universite Hastaneleri ( Site 2500)
        • Contact:
          • Study Coordinator
          • Phone Number: +905439340493
  • United Kingdom
      • Birmingham, United Kingdom, B15 2GW
        • Recruiting
        • University Hospitals Birmingham NHS Foundation Trust ( Site 2610)
        • Contact:
          • Study Coordinator
          • Phone Number: +4407789651543
    • Edinburgh, City of
      • Edinburgh, Edinburgh, City of, United Kingdom, EH4 2XU
        • Recruiting
        • Western General Hospital ( Site 2608)
        • Contact:
          • Study Coordinator
          • Phone Number: +441315371398
    • Leicestershire
      • Leicester, Leicestershire, United Kingdom, LE1 5WW
        • Recruiting
        • Leicester Royal Infirmary ( Site 2604)
        • Contact:
          • Study Coordinator
          • Phone Number: 0300 303 1573
    • Manchester
      • Withington, Manchester, United Kingdom, M20 4BX
        • Recruiting
        • The Christie Hospital NHS Foundation Trust ( Site 2601)
        • Contact:
          • Study Coordinator
          • Phone Number: 0161 918 2546
  • United States
    • Georgia
      • Marietta, Georgia, United States, 30060
        • Recruiting
        • Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital ( Site 0102)
        • Contact:
          • Study Coordinator
          • Phone Number: 770-281-5124
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine ( Site 0114)
        • Contact:
          • Study Coordinator
          • Phone Number: 314-362-7355
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center ( Site 0126)
        • Contact:
          • Study Coordinator
          • Phone Number: 347-798-9213
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • Recruiting
        • The West Clinic, P.C. ( Site 0115)
        • Contact:
          • Study Coordinator
          • Phone Number: 901-683-0055

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

  • 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

Exclusion Criteria:

For exclusion criteria: The main exclusion criteria include but are not limited to the following:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Belzutifan + Zanzalintinib
Participants will receive 120 mg belzutifan orally and 60 mg zanzalintinib once daily for approximately 24 months.
Drug: Belzutifan
Tablet for oral administration.
Other Names:
  • MK-6482
  • PT2977
  • WELIREG
Drug: Zanzalintinib
Tablet for oral administration.
Other Names:
  • XL092
Active Comparator: Belzutifan + Placebo
Participants will receive 120 mg belzutifan orally and zanzalintinib-matching placebo once daily for approximately 24 months.
Drug: Belzutifan
Tablet for oral administration.
Other Names:
  • MK-6482
  • PT2977
  • WELIREG
Drug: Placebo
Zanzalintinib-matching placebo tablet for oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS)
Time Frame: Up to approximately 30 months
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)
Time Frame: Up to approximately 50 months
OS is defined as the time from randomization to death due to any cause.
Up to approximately 50 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: Up to approximately 30 months
ORR is defined as the percentage of participants who have achieved confirmed 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 as assessed by BICR.
Up to approximately 30 months
Duration of Response (DOR)
Time Frame: Up to approximately 30 months
DOR is defined as the interval from the first documented evidence of a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 until Progressive Disease (PD) or death due to any cause, whichever occurs first, in participants demonstrating a best confirmed response of CR or PR. Per RECIST 1.1, PD is defined as at least a 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 at least 5 mm. The appearance of one or more new lesions is also considered PD.
Up to approximately 30 months
Number of Participants Who Experience One or More Adverse Events (AEs)
Time Frame: Up to approximately 25 months
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who experience an AE will be reported.
Up to approximately 25 months
Number of Participants who Discontinue Study Treatment Due to an AE
Time Frame: Up to approximately 24 months
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who discontinue study treatment due to an AE will be reported.
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
Time Frame: Baseline and up to approximately 25 months
EORTC QLQ-C30 is a questionnaire to assess the overall quality of life (QoL) of cancer patients. Participant responses to questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and QoL ("How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) is computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. The change from baseline in GHS and QoL combined score will be presented.
Baseline and up to approximately 25 months
Change from Baseline in the EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score
Time Frame: Baseline and up to approximately 25 months
EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 5 questions about their physical functioning (Items 1 to 5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 was computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. The change from baseline in EORTC QLQ-C30 physical functioning (Items 1-5) combined score will be presented.
Baseline and up to approximately 25 months
Change from Baseline in the EORTC QLQ-C30 Role Functioning (Items 6 and 7) Combined Score
Time Frame: Baseline and up to approximately 25 months
The EORTC QLQ-C30 is a cancer specific health-related quality of life questionnaire. The role functioning score is based on participant responses to questions scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score was computed by averaging the raw scores of Items 6 and 7 and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. Higher scores indicate better role functioning. The change from baseline in EORTC QLQ-C30 Role Functioning (Items 6 and 7) combined score will be reported.
Baseline and up to approximately 25 months
Change From Baseline in Disease Symptoms Using the Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease-related Symptoms (FKSI-DRS) (Items 1-9) Score
Time Frame: Baseline and up to approximately 25 months
The FKSI-DRS index consists of a 9-item questionnaire that assesses the extent of participant symptoms from kidney cancer. Each item is scored on a 5-point scale (0=not at all to 4=very much). FKSI-DRS total score ranged from 0 (most severe symptoms) to 36 (no symptoms) with a higher score indicating a better outcome.
Baseline and up to approximately 25 months
Time to Deterioration (TTD) in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score
Time Frame: Up to approximately 25 months
EORTC QLQ-C30 is a questionnaire to assess QoL of cancer patients. Participant responses to questions on GHS ("How would you rate your overall health during the past week?") and QoL ("How would you rate your overall QoL during the past week?") were scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) was computed by averaging raw scores of the 2 items and applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. TTD was defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in GHS-QoL combined score. A longer TTD indicates a better outcome.
Up to approximately 25 months
TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score
Time Frame: Up to approximately 25 months
EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 5 questions about their physical functioning (Items 1 to 5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 was computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. TTD was defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in physical functioning (Items 1 to 5). A longer TTD indicates a better outcome.
Up to approximately 25 months
TTD in EORTC QLQ-C30 Role Functioning (Items 6 and 7) Score
Time Frame: Up to approximately 25 months
EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to questions about their role functioning (Items 6 and 7) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of Items 6 and 7 was computed by averaging the raw scores of the items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. TTD was defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in role functioning (Items 6 and 7). A longer TTD indicates a better outcome.
Up to approximately 25 months
TTD in Disease Symptoms Using the FKSI-DRS (Items 1-9) Score
Time Frame: Up to approximately 25 months
TTD is defined as time from the first dose of study treatment to the date of deterioration of FKSI-DRS score. The FKSI-DRS index consists of a 9-item questionnaire that assesses the extent of participant symptoms from kidney cancer. Each item is scored on a 5-point scale (0=not at all to 4=very much). FKSI-DRS total score ranged from 0 (most severe symptoms) to 36 (no symptoms) with a higher score indicating a better outcome. Deterioration is defined as a 3-point decrease (i.e. lower score) in symptom score and the time to true deterioration is the time to first onset of 3 or more decreases from baseline with confirmation under right-censoring rule (the last observation). A longer TTD indicates a better outcome.
Up to approximately 25 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Collaborators

Exelixis

Investigators

  • Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 9, 2026

Primary Completion (Estimated)

November 27, 2030

Study Completion (Estimated)

November 27, 2030

Study Registration Dates

First Submitted

March 20, 2026

First Submitted That Met QC Criteria

March 20, 2026

First Posted (Actual)

March 24, 2026

Study Record Updates

Last Update Posted (Actual)

September 17, 2026

Last Update Submitted That Met QC Criteria

September 15, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 6482-034
  • U1111-1311-4692 (Registry Identifier: UTN)
  • 2024-516993-31-00 (Registry Identifier: EU CT)
  • LITESPARK-034 (Other Identifier: MSD)
  • MK-6482-034 (Other Identifier: MSD)
  • LS-034 (Other Identifier: MSD)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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