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

June 5, 2023 updated by: Merck Sharp & Dohme LLC

A Phase 1, Dose-escalation Study to Evaluate Safety and Tolerability of Belzutifan (MK-6482) in Participants With Advanced Clear Cell Renal Cell Carcinoma (ccRCC)

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).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

52

Phase

  • Phase 1

Contacts and Locations

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

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center ( Site 1002)
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan ( Site 1006)
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center-Vanderbilt-Ingram Cancer Center ( Site 1005)
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center-Genitourinary Medical Oncology ( Site 1007)

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

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: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Belzutifan 160 mg BID
Participants will receive belzutifan 160 mg orally twice daily (BID). Treatment will continue until progressive disease or discontinuation.
Drug: Belzutifan
40 mg tablet administered orally at a dose of 160 mg, 200 mg, or 120 mg.
Other Names:
  • MK-6482
  • PT2977
  • WELIREG™
Experimental: Belzutifan 160 mg TID
Participants will receive belzutifan 160 mg orally three times daily (TID). Treatment will continue until progressive disease or discontinuation.
Drug: Belzutifan
40 mg tablet administered orally at a dose of 160 mg, 200 mg, or 120 mg.
Other Names:
  • MK-6482
  • PT2977
  • WELIREG™
Experimental: Belzutifan 200 mg TID
Participants will receive belzutifan 200 mg orally TID. Treatment will continue until progressive disease or discontinuation.
Drug: Belzutifan
40 mg tablet administered orally at a dose of 160 mg, 200 mg, or 120 mg.
Other Names:
  • MK-6482
  • PT2977
  • WELIREG™
Experimental: Belzutifan 120 mg QD
Participants will receive belzutifan 120 mg orally once daily (QD). Treatment will continue until progressive disease or discontinuation.
Drug: Belzutifan
40 mg tablet administered orally at a dose of 160 mg, 200 mg, or 120 mg.
Other Names:
  • MK-6482
  • PT2977
  • WELIREG™

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Who Experience at Least One Adverse Event (AE)
Time Frame: Up to ~49.5 months
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
Time Frame: Up to ~48.5 months
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
Time Frame: Up to ~48.5 months
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)
Time Frame: Up to ~21 days
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area Under the Plasma Concentration Time Curve (AUC) of Belzutifan
Time Frame: 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
AUC is a measure of plasma drug concentration and time and is estimated as the area under the plot of plasma concentration against time after belzutifan administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine AUC.
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
Time Frame: 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
Cmax is the maximum concentration of belzutifan observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmax.
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
Time Frame: 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
Cmin is the minimum concentration of belzutifan observed in plasma after its administration and just prior to administration of a subsequent dose. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmin.
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

Collaborators and Investigators

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

Sponsor

Merck Sharp & Dohme LLC

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)

June 14, 2021

Primary Completion (Estimated)

July 17, 2025

Study Completion (Estimated)

July 17, 2025

Study Registration Dates

First Submitted

April 7, 2021

First Submitted That Met QC Criteria

April 13, 2021

First Posted (Actual)

April 15, 2021

Study Record Updates

Last Update Posted (Actual)

June 6, 2023

Last Update Submitted That Met QC Criteria

June 5, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 6482-018
  • MK-6482-018 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

http://engagezone.msd.com/doc/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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