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

NCT04489771 | Active Not Recruiting Phase 2 Results FDA Drug

• 4 other identifiers: 6482-013MK-6482-0132022-502123-21-002020-001907-18
• Study Type: interventional
• Target: 154
• Locations: 9 countries
• Sites: 48

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

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

Outcome Measures

Primary Outcomes (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.

  Up to approximately 27 months

Secondary Outcomes (8)

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

  Up to approximately 27 months

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

  Up to approximately 27 months

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

  Up to approximately 27 months

• Overall Survival (OS)

  Up to approximately 27 months

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

  Up to approximately 27 months

Study Arms (2)

Belzutifan 200 mg

EXPERIMENTAL

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

Drug: Belzutifan

Belzutifan 120 mg

EXPERIMENTAL

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

Drug: Belzutifan

Interventions

Belzutifan DRUG

Oral administration

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

Belzutifan 120 mg; Belzutifan 200 mg

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 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (48)

Georgetown University Medical Center ( Site 0002)

Washington D.C., District of Columbia, 20007, United States

Location

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

Miami, Florida, 33136, United States

Location

Norton Cancer Institute - St. Matthews ( Site 0025)

Louisville, Kentucky, 40207, United States

Location

Weinberg Cancer Institute at Franklin Square ( Site 0007)

Baltimore, Maryland, 21237, United States

Location

Cancer Partners of Nebraska ( Site 0003)

Lincoln, Nebraska, 68510, United States

Location

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

Omaha, Nebraska, 68130, United States

Location

New York Oncology Hematology P.C ( Site 0028)

Albany, New York, 12206, United States

Location

Roswell Park Cancer Institute ( Site 0038)

Buffalo, New York, 14263, United States

Location

Fox Chase Cancer Center ( Site 0026)

Philadelphia, Pennsylvania, 19111, United States

Location

Sanford Cancer Center Oncology Clinic ( Site 0031)

Sioux Falls, South Dakota, 57104, United States

Location

UT West Cancer Center ( Site 0032)

Germantown, Tennessee, 38138, United States

Location

Urology Associates ( Site 0015)

Nashville, Tennessee, 37209, United States

Location

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

Dallas, Texas, 75390, United States

Location

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

Temple, Texas, 76508, United States

Location

Huntsman Cancer Institute ( Site 0037)

Salt Lake City, Utah, 84112, United States

Location

Inova Schar Cancer Institute ( Site 0001)

Fairfax, Virginia, 22031, United States

Location

Blue Ridge Cancer Care - Roanoke ( Site 0017)

Roanoke, Virginia, 24014, United States

Location

Kadlec Clinic Hematology and Oncology ( Site 0008)

Kennewick, Washington, 99336, United States

Location

Macquarie University ( Site 1007)

Macquarie University, New South Wales, 2109, Australia

Location

Eastern Health - Box Hill Hospital ( Site 1003)

Box Hill, Victoria, 3128, Australia

Location

Peninsula Health Frankston Hospital ( Site 1001)

Frankston, Victoria, 3199, Australia

Location

GZA Sint Augustinus ( Site 2003)

Wilrijk, Antwerpen, 2610, Belgium

Location

Grand Hopital de Charleroi ( Site 2005)

Charleroi, Hainaut, 6000, Belgium

Location

CHU de Liege ( Site 2002)

Liège, Liege, 4000, Belgium

Location

UZ Gent ( Site 2004)

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

UZ Leuven ( Site 2001)

Leuven, Vlaams-Brabant, 3000, Belgium

Location

General Hospital of Athens "Alexandra" ( Site 1102)

Athens, Attica, 115 28, Greece

Location

Athens University Hospital ATTIKON ( Site 1100)

Chaïdári, Attica, 12 462, Greece

Location

University General Hospital of Larissa ( Site 1101)

Larissa, Thessaly, 411 10, Greece

Location

Cork University Hospital ( Site 9053)

Cork, T12 DC4A, Ireland

Location

Tallaght University Hospital ( Site 9051)

Dublin, D24 NR0A, Ireland

Location

Soroka Medical Center ( Site 4004)

Beersheba, 8410101, Israel

Location

Rambam Medical Center ( Site 4001)

Haifa, 3109601, Israel

Location

Rabin Medical Center ( Site 4002)

Petah Tikva, 4941492, Israel

Location

Sourasky Medical Center ( Site 4003)

Tel Aviv, 6423906, Israel

Location

Maastricht Universitair Medisch Centrum - MUMC ( Site 5001)

Maastricht, Limburg, 6202AZ, Netherlands

Location

Antoni van Leeuwenhoek Ziekenhuis ( Site 5003)

Amsterdam, North Holland, 1066 CX, Netherlands

Location

Isala klinieken ( Site 5002)

Zwolle, Overijssel, 8025 AB, Netherlands

Location

Erasmus MC ( Site 5000)

Rotterdam, South Holland, 3015 GD, Netherlands

Location

Universitair Medisch Centrum Utrecht ( Site 5004)

Utrecht, 3584 CX, Netherlands

Location

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

Moscow, Moscow, 117997, Russia

Location

City Clinical Oncology Hospital No. 1 ( Site 6004)

Moscow, Moscow, 129090, Russia

Location

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

Saint Petersburg, Sankt-Peterburg, 197758, Russia

Location

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

Saint Petersburg, Sankt-Peterburg, 197758, Russia

Location

Royal Free London NHS Foundation Trust ( Site 9003)

London, England, NW3 2QG, United Kingdom

Location

Imperial College Healthcare NHS Trust ( Site 9004)

London, London, City of, W6 8RF, United Kingdom

Location

Churchill Hospital ( Site 9000)

Oxford, Oxfordshire, OX3 7LE, United Kingdom

Location

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

Nottingham, NG5 1PB, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 39233312 RESULT

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms

Interventions

belzutifan

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; 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

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2020
• First Posted: July 28, 2020
• Study Start: September 13, 2020
• Primary Completion: February 10, 2023
• Study Completion (Estimated): October 4, 2026
• Last Updated: February 11, 2025
• Results First Posted: February 28, 2024

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

BE (5); GR (3); NL (5); IL (4); RU (4); AU (3); GB (4); US (18); IE (2)