Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04846920
Recruitment Status : Recruiting
First Posted : April 15, 2021
Last Update Posted : October 22, 2021
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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).

Condition or disease Intervention/treatment Phase
Carcinoma, Renal Cell Drug: Belzutifan Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 52 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : June 14, 2021
Estimated Primary Completion Date : July 17, 2025
Estimated Study Completion Date : July 17, 2025


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™




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04846920


Contacts
Layout table for location contacts
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
Layout table for location information
United States, Massachusetts
Beth Israel Deaconess Medical Center ( Site 1002) Recruiting
Boston, Massachusetts, United States, 02215
Contact: Study Coordinator    617-632-8543      
United States, Michigan
University of Michigan ( Site 1006) Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Study Coordinator    734-764-8195      
United States, Tennessee
Vanderbilt University Medical Center-Vanderbilt-Ingram Cancer Center ( Site 1005) Recruiting
Nashville, Tennessee, United States, 37232
Contact: Study Coordinator    615-322-4967      
United States, Texas
University of Texas MD Anderson Cancer Center-Genitourinary Medical Oncology ( Site 1007) Recruiting
Houston, Texas, United States, 77030
Contact: Study Coordinator    713-563-1930      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme Corp.
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT04846920    
Other Study ID Numbers: 6482-018
MK-6482-018 ( Other Identifier: Merck )
First Posted: April 15, 2021    Key Record Dates
Last Update Posted: October 22, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Sharp & Dohme Corp.:
Hypoxia inducible factor (HIF)
Hypoxia inducible factor 2 alpha (HIF-2α)
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases