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Carcinoma, Renal CellPhase 2NCT04489771

A Study of Belzutifan (MK-6482) in Participants With Advanced Renal Cell Carcinoma (MK-6482-013)

A Phase 2 study testing Belzutifan in people with Carcinoma, Renal Cell, run by Merck Sharp & Dohme LLC at 48 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study will compare the efficacy and safety of two doses of belzutifan in participants with advanced renal cell carcinoma (RCC) with clear cell component after prior therapy. The primary hypothesis is that the higher dose of belzutifan is superior to the standard dose in terms of objective response rate (ORR). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Renal Cell
What is being tested?
Belzutifan
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
154 participants
Where
48 sitesin 9 countries
Study dates
13 Sep 2020to 25 Aug 2026
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Has a histologically confirmed diagnosis of locally advanced/metastatic RCC with clear cell component
  • Has measurable disease per RECIST 1.1 as assessed by BICR
  • Can submit an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
  • Has experienced disease progression on or after systemic treatment with an anti-programmed cell death 1 (PD-1)/Ligand 1 (L1) therapy for locally advanced or metastatic RCC. The anti-PD-1/L1 therapy may be monotherapy or in combination with other agent(s) such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) or vascular endothelial growth factor (VEGF) targeted- tyrosine kinase inhibitor (TKI). The immediately preceding line of treatment has to have been an anti-PD-1/L1 therapy
  • Has received no more than 3 prior systemic regimens for locally advanced or metastatic RCC
  • Has received only 1 prior anti-PD-1/L1 therapy for locally advanced or metastatic RCC
Show all 11Show fewer
  • Has recovered from all AEs due to previous therapies to ≤Grade 1 or baseline, with the exception of ≤Grade 2 neuropathy or endocrine-related AEs ≤Grade 2 requiring treatment or hormone replacement
  • Has a Karnofsky performance status (KPS) score of at least 70% assessed within 10 days prior to the first dose of study intervention
  • A male participant is eligible to participate if he is abstinent from heterosexual intercourse or agrees to use contraception during the intervention period and for at least 7 days after the last dose of study intervention
  • A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a (woman of childbearing potential) WOCBP or a WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 30 days after the last dose of study intervention
  • A WOCBP must have a negative highly sensitive pregnancy test (urine or serum) within 24 hours before the first dose of study intervention

Who cannot join

  • Has hypoxia (a pulse oximeter reading <92% at rest), requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
  • Has a known additional malignancy that is progressing or has required active treatment within the past 3 years except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ [e.g., breast carcinoma, cervical cancer in situ] that have undergone potentially curative therapy
  • Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction ≤6 months from Day 1 of study drug administration or New York Heart Association Class III or IV congestive heart failure
  • Has moderate to severe hepatic impairment (Child-Pugh B or C)
  • Has received colony-stimulating factors (eg, granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], or recombinant erythropoietin [EPO]) ≤28 days prior to the first dose of study intervention
Show all 22Show fewer
  • Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study
  • Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (eg, gastrectomy, partial bowel obstruction, malabsorption)
  • Has known hypersensitivity or allergy to the active pharmaceutical ingredient or any component of the study intervention (belzutifan) formulations
  • Has received prior treatment with belzutifan or another hypoxia-inducible factor (HIF)-2α inhibitor
  • Has received any type of small molecule kinase inhibitor (including investigational kinase inhibitor) ≤2 weeks before randomization
  • Has received any type of systemic anticancer antibody (including investigational antibody) ≤4 weeks before randomization
  • Has received prior radiotherapy ≤2 weeks prior to first dose of study intervention. Participants must have recovered from all radiation-related toxicities and not require corticosteroids
  • Has had major surgery ≤3 weeks prior to first dose of study intervention
  • Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate (eg, bosentan, efavirenz, modafinil) inducers of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study
  • Is currently participating in a study of an investigational agent or is currently using an investigational device
  • Has an active infection requiring systemic therapy
  • Has active tuberculosis (TB)
  • Has a diagnosis of immunodeficiency
  • Has a known history of human immunodeficiency virus (HIV) infection
  • Has a known history of hepatitis B (HBV) or known active hepatitis C (HCV) infection
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not the best interest of the participant to participate, in the opinion of the treating investigator

Trial locations and contacts

48 sites in 9 countries.

48 sites in 9 countries

United States18 sites

  • New York Oncology Hematology P.C ( Site 0028)

    Albany, New York, 12206

  • Weinberg Cancer Institute at Franklin Square ( Site 0007)

    Baltimore, Maryland, 21237

  • Roswell Park Cancer Institute ( Site 0038)

    Buffalo, New York, 14263

  • University of Texas Southwestern Medical Center at Dallas ( Site 0004)

    Dallas, Texas, 75390

  • Inova Schar Cancer Institute ( Site 0001)

    Fairfax, Virginia, 22031

  • UT West Cancer Center ( Site 0032)

    Germantown, Tennessee, 38138

  • Kadlec Clinic Hematology and Oncology ( Site 0008)

    Kennewick, Washington, 99336

  • Cancer Partners of Nebraska ( Site 0003)

    Lincoln, Nebraska, 68510

  • Norton Cancer Institute - St. Matthews ( Site 0025)

    Louisville, Kentucky, 40207

  • Univ of Miami- Sylvester Comprehensive Cancer Center ( Site 0023)

    Miami, Florida, 33136

  • Urology Associates ( Site 0015)

    Nashville, Tennessee, 37209

  • Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0012)

    Omaha, Nebraska, 68130

  • Fox Chase Cancer Center ( Site 0026)

    Philadelphia, Pennsylvania, 19111

  • Blue Ridge Cancer Care - Roanoke ( Site 0017)

    Roanoke, Virginia, 24014

  • Huntsman Cancer Institute ( Site 0037)

    Salt Lake City, Utah, 84112

  • Sanford Cancer Center Oncology Clinic ( Site 0031)

    Sioux Falls, South Dakota, 57104

  • Baylor Scott & White Medical Center - Temple ( Site 0013)

    Temple, Texas, 76508

  • Georgetown University Medical Center ( Site 0002)

    Washington D.C., District of Columbia, 20007

Other trials in United States

Belgium5 sites

  • Grand Hopital de Charleroi ( Site 2005)

    Charleroi, Hainaut, 6000

  • UZ Gent ( Site 2004)

    Ghent, Oost-Vlaanderen, 9000

  • UZ Leuven ( Site 2001)

    Leuven, Vlaams-Brabant, 3000

  • CHU de Liege ( Site 2002)

    Liège, Liege, 4000

  • GZA Sint Augustinus ( Site 2003)

    Wilrijk, Antwerpen, 2610

Other trials in Belgium

Netherlands5 sites

  • Antoni van Leeuwenhoek Ziekenhuis ( Site 5003)

    Amsterdam, North Holland, 1066 CX

  • Maastricht Universitair Medisch Centrum - MUMC ( Site 5001)

    Maastricht, Limburg, 6202AZ

  • Erasmus MC ( Site 5000)

    Rotterdam, South Holland, 3015 GD

  • Universitair Medisch Centrum Utrecht ( Site 5004)

    Utrecht, 3584 CX

  • Isala klinieken ( Site 5002)

    Zwolle, Overijssel, 8025 AB

Other trials in Netherlands

Israel4 sites

  • Soroka Medical Center ( Site 4004)

    Beersheba, 8410101

  • Rambam Medical Center ( Site 4001)

    Haifa, 3109601

  • Rabin Medical Center ( Site 4002)

    Petah Tikva, 4941492

  • Sourasky Medical Center ( Site 4003)

    Tel Aviv, 6423906

Other trials in Israel

Russia4 sites

  • Federal state budgetary institution Russian Research Centre of radiology and nuclear medicine ( Site

    Moscow, Moscow, 117997

  • City Clinical Oncology Hospital No. 1 ( Site 6004)

    Moscow, Moscow, 129090

  • Clinical Research Center of specialized types medical care-Oncology ( Site 6002)

    Saint Petersburg, Sankt-Peterburg, 197758

  • Russian Scientific Center of Radiology and Surgical Technologies ( Site 6001)

    Saint Petersburg, Sankt-Peterburg, 197758

Other trials in Russia

United Kingdom4 sites

  • Royal Free London NHS Foundation Trust ( Site 9003)

    London, England, NW3 2QG

  • Imperial College Healthcare NHS Trust ( Site 9004)

    London, London, City of, W6 8RF

  • Nottingham University Hospitals NHS Trust. City Hospital Campus ( Site 9001)

    Nottingham, NG5 1PB

  • Churchill Hospital ( Site 9000)

    Oxford, Oxfordshire, OX3 7LE

Other trials in United Kingdom

Australia3 sites

  • Eastern Health - Box Hill Hospital ( Site 1003)

    Box Hill, Victoria, 3128

  • Peninsula Health Frankston Hospital ( Site 1001)

    Frankston, Victoria, 3199

  • Macquarie University ( Site 1007)

    Macquarie University, New South Wales, 2109

Other trials in Australia

Greece3 sites

  • General Hospital of Athens "Alexandra" ( Site 1102)

    Athens, Attica, 115 28

  • Athens University Hospital ATTIKON ( Site 1100)

    Chaïdári, Attica, 12 462

  • University General Hospital of Larissa ( Site 1101)

    Larissa, Thessaly, 411 10

Other trials in Greece

Ireland2 sites

  • Cork University Hospital ( Site 9053)

    Cork, T12 DC4A

  • Tallaght University Hospital ( Site 9051)

    Dublin, D24 NR0A

Other trials in Ireland

About this study

Official title: Phase 2 Study of MK-6482 in Participants With Advanced Renal Cell Carcinoma

This study will compare the efficacy and safety of two doses of belzutifan in participants with advanced renal cell carcinoma (RCC) with clear cell component after prior therapy.

The primary hypothesis is that the higher dose of belzutifan is superior to the standard dose in terms of objective response rate (ORR).

Being tested
Belzutifan
Keywords
Hypoxia inducible factor (HIF), Hypoxia inducible factor 1B (HIF-1B), Hypoxia inducible factor 2 alpha (HIF-2 alpha), Hypoxia inducible factor 2α (HIF-2α), Renal Cell Carcinoma (RCC), Kidney cancer
Medical subject headings
Carcinoma, Renal Cell, Kidney Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BelzutifanDrug

    Also called MK-6482, PT2977, WELIREG™

    Oral administration

Study groups in NCT04489771
Study groupRoleWhat they receive
Belzutifan 200 mgExperimentalParticipants receive 200 mg of belzutifan by oral administration, once a day (QD), until disease progression or discontinuation.
Receives: Drug: Belzutifan
Belzutifan 120 mgExperimentalParticipants receive 120 mg of belzutifan by oral administration, QD, until disease progression or discontinuation.
Receives: Drug: Belzutifan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)

    ORR was defined as the percentage of participants who had a 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. The percentage of participants who experienced a CR or PR as assessed by blinded independent central review based on RECIST 1.1 was presented.

    Measured: Up to approximately 27 months

Secondary outcomes (8)

  1. Progression-Free Survival (PFS) According to RECIST 1.1 as Assessed by BICR

    PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was 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 was also considered PD. PFS as assessed by blinded independent central review was presented.

    Measured: Up to approximately 27 months

  2. Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR

    For participants who demonstrated a confirmed complete response (CR: Disappearance of all target lesions) or confirmed partial response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. The DOR as assessed by blinded independent central review was presented.

    Measured: Up to approximately 27 months

  3. Clinical Benefit Rate (CBR) Per RECIST 1.1 as Assessed by BICR

    CBR is defined as the percentage of participants who have a 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) or stable disease (SD: Neither sufficient decrease to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.) ≥6 months per RECIST 1.1. The percentage of participants with CBR will be presented.

    Measured: Up to approximately 27 months

  4. Overall Survival (OS)

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

    Measured: Up to approximately 27 months

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

    An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experienced one or more AEs was presented.

    Measured: Up to approximately 27 months

  6. Number of Participants Who Discontinue Study Treatment Due to an AE

    An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued study treatment due to an AE was presented.

    Measured: Up to approximately 26 months

  7. Maximum Plasma Concentration (Cmax) of Belzutifan

    Blood samples were obtained at designated time points for the determination of the Cmax of belzutifan.

    Measured: Weeks 1 and 3 on Day 1: predose and 1, 2, and 4 hours. Week 5 on Day 1: predose only

  8. Trough Plasma Concentration (Ctrough) of Belzutifan

    Blood samples were obtained at designated time points for the determination of the Ctrough of belzutifan.

    Measured: Weeks 1 and 3 on Day 1: predose and 1, 2, and 4 hours. Week 5 on Day 1: predose only

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jul 2020
  2. Study start13 Sep 2020
  3. Primary completion10 Feb 2023
  4. Study completion25 Aug 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
154 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04489771
Sponsor's protocol ID
6482-013
Other IDs
MK-6482-013, 2022-502123-21-00, U1111-1283-3731, 2020-001907-18
Status last verified
Sep 2026
First submitted
27 Jul 2020
Last updated
24 Sep 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

  • Agarwal N, Brugarolas J, Ghatalia P, George S, Haanen JB, Gurney H, Ravilla R, Van der Veldt A, Beuselinck B, Pokataev I, Suelmann BBM, Tuthill MH, Vaena D, Zagouri F, Wu J, Perini RF, Liu Y, Merchan J, Atkins MB. Randomized phase II dose comparison LITESPARK-013 study of belzutifan in patients with advanced clear cell renal cell carcinoma. Ann Oncol. 2024 Dec;35(12):1148-1156. doi: 10.1016/j.annonc.2024.08.2338. Epub 2024 Sep 2.

    PubMed 39233312

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Belzutifan in people with Carcinoma, Renal Cell, run by Merck Sharp & Dohme LLC at 48 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 48 sites in United States, Belgium, Netherlands, Israel, Russia and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) (time frame: Up to approximately 27 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04489771, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2026.

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