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

NCT ID: NCT04489771

Last Updated: 2025-02-11

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 154 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-13
• Study Completion Date: 2026-10-04

Brief 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).

Conditions

Carcinoma, Renal Cell

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Belzutifan 200 mg

Participants receive 200 mg of belzutifan by oral administration, once a day (QD), until disease progression or discontinuation.

Group Type: EXPERIMENTAL

Belzutifan

Intervention Type: DRUG

Oral administration

Belzutifan 120 mg

Participants receive 120 mg of belzutifan by oral administration, QD, until disease progression or discontinuation.

Group Type: EXPERIMENTAL

Belzutifan

Intervention Type: DRUG

Oral administration

Interventions

Belzutifan

Oral administration

Intervention Type: DRUG

Other Intervention Names

MK-6482; PT2977; WELIREG™

Eligibility Criteria

Inclusion Criteria

• 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
• 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

Exclusion Criteria

• 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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Georgetown University Medical Center ( Site 0002)

Washington D.C., District of Columbia, United States

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

Miami, Florida, United States

Norton Cancer Institute - St. Matthews ( Site 0025)

Louisville, Kentucky, United States

Weinberg Cancer Institute at Franklin Square ( Site 0007)

Baltimore, Maryland, United States

Cancer Partners of Nebraska ( Site 0003)

Lincoln, Nebraska, United States

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

Omaha, Nebraska, United States

New York Oncology Hematology P.C ( Site 0028)

Albany, New York, United States

Roswell Park Cancer Institute ( Site 0038)

Buffalo, New York, United States

Fox Chase Cancer Center ( Site 0026)

Philadelphia, Pennsylvania, United States

Sanford Cancer Center Oncology Clinic ( Site 0031)

Sioux Falls, South Dakota, United States

UT West Cancer Center ( Site 0032)

Germantown, Tennessee, United States

Urology Associates ( Site 0015)

Nashville, Tennessee, United States

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

Dallas, Texas, United States

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

Temple, Texas, United States

Huntsman Cancer Institute ( Site 0037)

Salt Lake City, Utah, United States

Inova Schar Cancer Institute ( Site 0001)

Fairfax, Virginia, United States

Blue Ridge Cancer Care - Roanoke ( Site 0017)

Roanoke, Virginia, United States

Kadlec Clinic Hematology and Oncology ( Site 0008)

Kennewick, Washington, United States

Macquarie University ( Site 1007)

Macquarie University, New South Wales, Australia

Eastern Health - Box Hill Hospital ( Site 1003)

Box Hill, Victoria, Australia

Peninsula Health Frankston Hospital ( Site 1001)

Frankston, Victoria, Australia

GZA Sint Augustinus ( Site 2003)

Wilrijk, Antwerpen, Belgium

Grand Hopital de Charleroi ( Site 2005)

Charleroi, Hainaut, Belgium

CHU de Liege ( Site 2002)

Liège, Liege, Belgium

UZ Gent ( Site 2004)

Ghent, Oost-Vlaanderen, Belgium

UZ Leuven ( Site 2001)

Leuven, Vlaams-Brabant, Belgium

General Hospital of Athens "Alexandra" ( Site 1102)

Athens, Attica, Greece

Athens University Hospital ATTIKON ( Site 1100)

Chaïdári, Attica, Greece

University General Hospital of Larissa ( Site 1101)

Larissa, Thessaly, Greece

Cork University Hospital ( Site 9053)

Cork, , Ireland

Tallaght University Hospital ( Site 9051)

Dublin, , Ireland

Soroka Medical Center ( Site 4004)

Beersheba, , Israel

Rambam Medical Center ( Site 4001)

Haifa, , Israel

Rabin Medical Center ( Site 4002)

Petah Tikva, , Israel

Sourasky Medical Center ( Site 4003)

Tel Aviv, , Israel

Maastricht Universitair Medisch Centrum - MUMC ( Site 5001)

Maastricht, Limburg, Netherlands

Antoni van Leeuwenhoek Ziekenhuis ( Site 5003)

Amsterdam, North Holland, Netherlands

Isala klinieken ( Site 5002)

Zwolle, Overijssel, Netherlands

Erasmus MC ( Site 5000)

Rotterdam, South Holland, Netherlands

Universitair Medisch Centrum Utrecht ( Site 5004)

Utrecht, , Netherlands

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

Moscow, Moscow, Russia

City Clinical Oncology Hospital No. 1 ( Site 6004)

Moscow, Moscow, Russia

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

Saint Petersburg, Sankt-Peterburg, Russia

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

Saint Petersburg, Sankt-Peterburg, Russia

Royal Free London NHS Foundation Trust ( Site 9003)

London, England, United Kingdom

Imperial College Healthcare NHS Trust ( Site 9004)

London, London, City of, United Kingdom

Churchill Hospital ( Site 9000)

Oxford, Oxfordshire, United Kingdom

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

Nottingham, , United Kingdom

Countries

United States; Australia; Belgium; Greece; Ireland; Israel; Netherlands; Russia; United Kingdom

References

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.

Reference Type: RESULT

PMID: 39233312 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.merckclinicaltrials.com/

Merck Clinical Trials Information

https://msd.trialsummaries.com/Study/StudyDetails?id=26234&tenant=MT_MSD_9011

Plain Language Summary

Other Identifiers

MK-6482-013

Identifier Type: OTHER

Identifier Source: secondary_id

2022-502123-21-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

2020-001907-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

6482-013

Identifier Type: -

Identifier Source: org_study_id