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)
Overview
- Phase
- Phase 1
- Intervention
- Belzutifan
- Conditions
- Carcinoma, Renal Cell
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 52
- Locations
- 4
- Primary Endpoint
- Percentage of Participants Who Modify or Interrupt Study Treatment Due to an AE
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
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).
Investigators
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.
Arms & Interventions
Belzutifan 160 mg BID
Participants will receive belzutifan 160 mg orally twice daily (BID). Treatment will continue until progressive disease or discontinuation.
Intervention: Belzutifan
Belzutifan 160 mg TID
Participants will receive belzutifan 160 mg orally three times daily (TID). Treatment will continue until progressive disease or discontinuation.
Intervention: Belzutifan
Belzutifan 200 mg TID
Participants will receive belzutifan 200 mg orally TID. Treatment will continue until progressive disease or discontinuation.
Intervention: Belzutifan
Belzutifan 120 mg QD
Participants will receive belzutifan 120 mg orally once daily (QD). Treatment will continue until progressive disease or discontinuation.
Intervention: Belzutifan
Outcomes
Primary Outcomes
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.
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.
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.
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.
Secondary Outcomes
- 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)
- 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)
- 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)