A Study of Belzutifan (MK-6482) as Monotherapy and in Combination With Lenvatinib (E7080/MK-7902) With or Without Pembrolizumab (MK-3475) in China Participants With Advanced Renal Cell Carcinoma (MK-6482-010)
- Conditions
- Renal Cell Carcinoma
- Interventions
- Registration Number
- NCT05030506
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profiles, and preliminary efficacy of belzutifan as monotherapy followed by belzutifan+lenvatinib combination therapy, as well as belzutifan combined with lenvatinib and pembrolizumab in China participants with advanced renal cell carcinoma.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 45
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Belzutifan + Lenvatinib Belzutifan Participants will receive a daily oral dose of 120 mg of belzutifan monotherapy for 3 weeks, followed by a combination of a daily oral dose of 120 mg of belzutifan with a daily oral dose of 20 mg of lenvatinib until progressive disease or discontinuation. Belzutifan + Lenvatinib Lenvatinib Participants will receive a daily oral dose of 120 mg of belzutifan monotherapy for 3 weeks, followed by a combination of a daily oral dose of 120 mg of belzutifan with a daily oral dose of 20 mg of lenvatinib until progressive disease or discontinuation. Belzutifan + Lenvatinib + Pembrolizumab Pembrolizumab Participants will receive an intravenous dose of 400 mg of pembrolizumab once every six weeks for up to 18 infusions (up to 2 years) in combination with a daily oral dose of 120 mg of belzutifan and a daily oral dose of 20 mg of lenvatinib until progressive disease or discontinuation. Belzutifan + Lenvatinib + Pembrolizumab Lenvatinib Participants will receive an intravenous dose of 400 mg of pembrolizumab once every six weeks for up to 18 infusions (up to 2 years) in combination with a daily oral dose of 120 mg of belzutifan and a daily oral dose of 20 mg of lenvatinib until progressive disease or discontinuation. Belzutifan + Lenvatinib + Pembrolizumab Belzutifan Participants will receive an intravenous dose of 400 mg of pembrolizumab once every six weeks for up to 18 infusions (up to 2 years) in combination with a daily oral dose of 120 mg of belzutifan and a daily oral dose of 20 mg of lenvatinib until progressive disease or discontinuation.
- Primary Outcome Measures
Name Time Method Number of participants who discontinued study treatment due to an AE Up to approximately 20 months An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who discontinued from the study treatment due to an AE will be reported.
Area under the concentration-time curve from 0-24 hours (AUC0-24) of belzutifan after single dose (Cohort 1) Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose 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 drug administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine AUC0-24 of belzutifan.
Maximum concentration (Cmax) of belzutifan after single dose (Cohort 1) Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose Cmax is the maximum concentration of the drug observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmax of belzutifan.
Time at maximum concentration (Tmax) of belzutifan after single dose (Cohort 1) Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose Tmax is the amount of time that a drug is present at the maximum concentration is observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine the Tmax of belzutifan.
Steady state area under the concentration-time curve from 0-24 hours (AUC0-24,ss) of belzutifan after multiple doses (Cohort 1) Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose AUC0-24,ss is a measure of plasma drug concentration and time and is estimated as the area under the plot of plasma concentration against time after drug administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine AUC0-24,ss of belzutifan.
Steady state maximum concentration (Cmax,ss) of belzutifan after multiple doses (Cohort 1) Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose Cmax,ss is the maximum concentration of the drug observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmax,ss of belzutifan.
Time at maximum concentration (Tmax) of belzutifan after multiple doses (Cohort 1) Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose Tmax is the amount of time that a drug is present at the maximum concentration is observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine the Tmax of belzutifan.
Apparent t½ of belzutifan after multiple doses (Cohort 1) Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose. T1/2 is a measure of how long it takes to clear 50% of the drug after reaching Cmax. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine t1/2 of belzutifan.
Steady state trough concentration (Ctrough,ss) of belzutifan after multiple doses (Cohort 1) Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose Ctrough,ss is the lowest concentration reached by a drug before the next dose is administered. Blood samples taken at predose and at specified times post dose will be used to determine Ctrough,ss of belzutifan.
Accumulation ratio (RAC) of belzutifan after multiple doses (Cohort 1) Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose RAC is the ratio of accumulation of a drug under steady state conditions after repeated administration as compared to a single dose. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine RAC of belzutifan.
Apparent oral clearance (CL/F) of belzutifan after multiple doses (Cohort 1) Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose CL/F is the apparent total clearance of the drug from plasma after oral administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine CL/F of belzutifan.
Apparent oral volume (Vz/F) of belzutifan after multiple doses (Cohort 1) Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose Vz/F is the apparent volume of distribution of the drug during terminal phase after non-intravenous administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Vz/F of belzutifan.
Number of participants who experienced dose-limiting toxicities (DLTs) Up to approximately 21 days A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0). Number of participants who experience a DLT per CTCAE 5.0 will be reported.
Number of participants who experienced an adverse event (AE) Up to approximately 20 months An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who experience an AE in the study will be reported.
- Secondary Outcome Measures
Name Time Method Objective response rate (ORR) Up to approximately 20 months ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1.) The percentage of participants who experience a CR or PR as assessed by blinded independent central review based on RECIST 1.1 will be presented.
Duration of response (DOR) Up to approximately 20 months For participants who demonstrate a confirmed Complete Response (CR: Disappearance of all target lesions) or confirmed Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. The DOR as assessed by blinded independent central review will be presented.
Progression-free survival (PFS) Up to approximately 20 months PFS is defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review will be presented.
Overall survival (OS) Up to approximately 20 months OS, defined as the time from first dose of study treatment to death due to any cause, will be presented.
Steady state trough concentration (Ctrough,ss) of belzutifan (Cohort 2) Pre-dose, and 1, 2 and 4 hours postdose Cmin,ss is the minimum plasma drug concentration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmin,ss of belzutifan.
Percent change from baseline in erythropoietin (EPO) level Baseline, up to approximately 6 weeks Percent change from baseline in EPO level will be measured and presented.
Cmax,ss of belzutifan for UGT2B17 and CYP2C19 phenotypes Week 3 Day 7: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose Cmax,ss is the maximum concentration of the drug observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmax,ss of belzutifan for participants with UGT2B17 and CYP2C19 phenotypes.
AUCss of belzutifan for UGT2B17 and CYP2C19 phenotypes Week 3 Day 7: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose AUC0-24,ss is a measure of plasma drug concentration vs time and is estimated as the area under the plot of plasma concentration against time after drug administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine AUC0-24,ss of belzutifan for participants with UGT2B17 and CYP2C19 phenotypes.
Ctrough,ss of belzutifan for UGT2B17 and CYP2C19 phenotypes Week 3 Day 7: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose Ctrough,ss is the lowest concentration reached by a drug before the next dose is administered. Blood samples taken at predose and at specified times post dose will be used to determine Ctrough,ss of belzutifan for participants with UGT2B17 and CYP2C19 phenotypes.
Trial Locations
- Locations (5)
Tianjin Medical University Cancer Institute and Hospital ( Site 0003)
🇨🇳Tianjin, Tianjin, China
Beijing Cancer hospital-Digestive Oncology ( Site 0001)
🇨🇳Beijing, Beijing, China
Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School-Urology ( S
🇨🇳Nanjing, Jiangsu, China
The Second Affiliated hospital of Zhejiang University school of medicine-Urology ( Site 0007)
🇨🇳Hangzhou, Zhejiang, China
SUN YAT-SEN UNIVERSITY CANCER CENTRE-Urology Surgery Department ( Site 0005)
🇨🇳Guangzhou, Guangdong, China