A Study of Belzutifan (MK-6482) in Participants With Advanced Clear Cell Renal Cell Carcinoma (MK-6482-018)

NCT04846920 | Completed Phase 1 FDA Drug

• 2 other identifiers: 6482-018MK-6482-018
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 4

Brief Summary

The goal of this study is to evaluate the safety, tolerability and pharmacokinetics of escalating doses of belzutifan as second line positive (2L+) treatment in participants with advanced clear cell renal cell carcinoma (ccRCC).

Conditions

Carcinoma, Renal Cell

Keywords

Hypoxia inducible factor (HIF); Hypoxia inducible factor 2 alpha (HIF-2α)

Outcome Measures

Primary Outcomes (4)

• Percentage of Participants Who Experience at Least One Adverse Event (AE)

  An AE is 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 percentage of participants who experience at least one AE will be reported.

  Up to ~49.5 months

• Percentage of Participants Who Discontinue Study Treatment Due to an AE

  An AE is 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 percentage of participants who discontinue study treatment due to an AE will be reported.

  Up to ~48.5 months

• Percentage of Participants Who Modify or Interrupt Study Treatment Due to an AE

  An AE is 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 percentage of participants who modify or interrupt study treatment due to an AE will be reported.

  Up to ~48.5 months

• Percentage of Participants Who Experience at Least One Dose-limiting Toxicity (DLT)

  A DLT consists of one or more of the following toxicities: (1) Grade 3 or 4 hypoxia or dyspnea (2) Grade 3 or 4 nausea, vomiting, or diarrhea if persistent for \>48 hours despite therapy (3) Grade 3 or 4 cardiovascular, vascular, or thrombotic events (4) Nonhematologic AE ≥Grade 3 in severity (5) Grade 4 nonhematologic toxicity (6) Grade 3 or 4 hematologic toxicities (7) Grade 3 or 4 febrile neutropenia (8) Grade 3 or 4 nonhematologic laboratory value (9) \>2 weeks delay in dosing due to intervention-related toxicity (10) Intervention-related toxicity causing intervention discontinuation in the first 21 days of dosing (11) Missing \>20% of belzutifan doses due to drug-related AEs in the first 21 days. (12) Grade 5 toxicity. The percentage of participants who experience at least one DLT will be reported.

  Up to ~21 days

Secondary Outcomes (3)

• Area Under the Plasma Concentration Time Curve (AUC) of Belzutifan

  Day 1, Day 21: pre-dose, 0.5, 1, 1.5, 2, 4, and 6 hours post-dose; Day 2: pre-dose and 2 hours post-dose

• Maximum Observed Plasma Concentration (Cmax) of Belzutifan

  Day 1, Day 21: pre-dose, 0.5, 1, 1.5, 2, 4, and 6 hours post-dose; Day 2: pre-dose and 2 hours post-dose

• Minimum Observed Plasma Concentration (Cmin) of Belzutifan

  Day 1, Day 21: pre-dose, 0.5, 1, 1.5, 2, 4, and 6 hours post-dose; Day 2: pre-dose and 2 hours post-dose

Study Arms (4)

Belzutifan 160 mg BID

EXPERIMENTAL

Participants will receive belzutifan 160 mg orally twice daily (BID). Treatment will continue until progressive disease or discontinuation.

Drug: Belzutifan

Belzutifan 160 mg TID

EXPERIMENTAL

Participants will receive belzutifan 160 mg orally three times daily (TID). Treatment will continue until progressive disease or discontinuation.

Drug: Belzutifan

Belzutifan 200 mg TID

EXPERIMENTAL

Participants will receive belzutifan 200 mg orally TID. Treatment will continue until progressive disease or discontinuation.

Drug: Belzutifan

Belzutifan 120 mg QD

EXPERIMENTAL

Participants will receive belzutifan 120 mg orally once daily (QD). Treatment will continue until progressive disease or discontinuation.

Drug: Belzutifan

Interventions

Belzutifan DRUG

40 mg tablet administered orally at a dose of 160 mg, 200 mg, or 120 mg.

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

Belzutifan 120 mg QD; Belzutifan 160 mg BID; Belzutifan 160 mg TID; Belzutifan 200 mg TID

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, locally advanced/metastatic RCC with clear cell component (with or without sarcomatoid features) (may include participants with a diagnosis of von Hippel-Lindau \[VHL\] associated ccRCC).
• Has experienced disease progression on or after having received at least one previous systemic treatment for advanced ccRCC.
• Shows adequate organ function.
• Male participants are eligible to participate if they are abstinent from heterosexual intercourse or agree 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 or breastfeeding, and is not a woman of childbearing potential (WOCBP) or is a WOCBP and using contraception or is abstinent from heterosexual intercourse during the intervention period and for at least 30 days after the last dose of study intervention.

You may not qualify if:

• Has hypoxia, or 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. Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in situ cancers.
• Has any history of or current brain or meningeal metastasis.
• Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass graft surgery (CABG) ≤6 months from Day 1 of study drug administration, or New York Heart Association Class III or IV congestive heart failure. Medically controlled arrhythmia stable on medication is permitted.
• Has moderate to severe hepatic impairment.
• Has an active infection requiring therapy (includes tuberculosis).
• Has known human immunodeficiency virus (HIV) and/or hepatitis B or C infections or is known to be positive for hepatitis B surface antigen (HBsAg)/hepatitis B virus (HBV) deoxy ribonucleic acid (DNA) or hepatitis C antibody or ribonucleic acid (RNA).
• Has a history or current evidence of a gastrointestinal (GI) condition (eg, inflammatory bowel disease, Crohn's disease, ulcerative colitis) or impaired liver function.
• Has had major surgery ≤3 weeks prior to first dose of study intervention.
• Has received prior treatment with belzutifan.
• Has received any type of systemic anticancer antibody (including investigational antibody) ≤4 weeks prior to the first dose of study intervention.
• Has recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline. Participants with a ≤ Grade 2 neuropathy may be eligible.
• Has received prior radiotherapy within 2 weeks prior to randomization.
• Has received colony-stimulating factors (CSFs) (e.g., granulocyte-CSF \[G-CSF\], granulocyte monocyte-CSF \[GM-CSF\] or recombinant erythropoietin \[EPO\]) ≤28 days prior to the first dose of study intervention.
• Has participated and received study intervention in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been at least 4 weeks since the last dose of the previous investigational agent.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (4)

Beth Israel Deaconess Medical Center ( Site 1002)

Boston, Massachusetts, 02215, United States

Location

University of Michigan ( Site 1006)

Ann Arbor, Michigan, 48109, United States

Location

Vanderbilt University Medical Center-Vanderbilt-Ingram Cancer Center ( Site 1005)

Nashville, Tennessee, 37232, United States

Location

University of Texas MD Anderson Cancer Center-Genitourinary Medical Oncology ( Site 1007)

Houston, Texas, 77030, United States

Location

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The "Belzutifan 160 mg BID", "Belzutifan 160 mg TID" and "Belzutifan 200 mg TID" study arms will be enrolled sequentially; the "Belzutifan 120 mg QD" study arm will be enrolled in parallel to the "Belzutifan 160 mg BID", "Belzutifan 160 mg TID" and "Belzutifan 200 mg TID" arms.

Study Record Dates

• First Submitted: April 7, 2021
• First Posted: April 15, 2021
• Study Start: June 14, 2021
• Primary Completion: April 11, 2026
• Study Completion: April 11, 2026
• Last Updated: May 22, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

US (4)