Purpose

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 Design

Phase
Phase 1
Study Type
Interventional
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.
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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™

Recruiting Locations

Vanderbilt University Medical Center-Vanderbilt-Ingram Cancer Center ( Site 1005)
Nashville, Tennessee 37232
Contact:
Study Coordinator
615-322-4967

More Details

Status
Recruiting
Sponsor
Merck Sharp & Dohme Corp.

Study Contact

Toll Free Number
1-888-577-8839
Trialsites@merck.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.