Description:
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).
Title
- Brief Title: A Study of Belzutifan (MK-6482) in Participants With Advanced Clear Cell Renal Cell Carcinoma (MK-6482-018)
- 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)
Clinical Trial IDs
- ORG STUDY ID:
6482-018
- SECONDARY ID:
MK-6482-018
- NCT ID:
NCT04846920
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Belzutifan | MK-6482, PT2977, WELIREG™ | Belzutifan 120 mg QD |
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).
Trial Arms
Name | Type | Description | Interventions |
---|
Belzutifan 160 mg BID | Experimental | Participants will receive belzutifan 160 mg orally twice daily (BID). Treatment will continue until progressive disease or discontinuation. | |
Belzutifan 160 mg TID | Experimental | Participants will receive belzutifan 160 mg orally three times daily (TID). Treatment will continue until progressive disease or discontinuation. | |
Belzutifan 200 mg TID | Experimental | Participants will receive belzutifan 200 mg orally TID. Treatment will continue until progressive disease or discontinuation. | |
Belzutifan 120 mg QD | Experimental | Participants will receive belzutifan 120 mg orally once daily (QD). Treatment will continue until progressive disease or discontinuation. | |
Eligibility 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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Percentage of Participants Who Experience at Least One Adverse Event (AE) |
Time Frame: | Up to ~49.5 months |
Safety Issue: | |
Description: | 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. |
Secondary Outcome Measures
Measure: | 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 |
Safety Issue: | |
Description: | 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. |
Measure: | 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 |
Safety Issue: | |
Description: | 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. |
Measure: | 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 |
Safety Issue: | |
Description: | 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. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Merck Sharp & Dohme Corp. |
Trial Keywords
- Hypoxia inducible factor (HIF)
- Hypoxia inducible factor 2 alpha (HIF-2α)
Last Updated
September 1, 2021