An Open-Label, Phase 1 Study of MK-6482 as Monotherapy and in Combination With Lenvatinib (MK-7902) With or Without Pembrolizumab (MK-3475) in China Participants With Advanced Renal Cell Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 45
- 试验地点
- 5
- 主要终点
- Number of participants who experienced dose-limiting toxicities (DLTs)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Belzutifan + 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.
干预措施: Lenvatinib (Drug)
Belzutifan + 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.
干预措施: Belzutifan (Drug)
Belzutifan + Lenvatinib + 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.
干预措施: Belzutifan (Drug)
Belzutifan + Lenvatinib + 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.
干预措施: Pembrolizumab (Biological)
Belzutifan + Lenvatinib + 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.
干预措施: Lenvatinib (Drug)
结局指标
主要结局
Number of participants who experienced dose-limiting toxicities (DLTs)
时间窗: 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)
时间窗: Up to approximately 68 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.
Number of participants who discontinued study treatment due to an AE
时间窗: Up to approximately 68 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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.
次要结局
- Objective response rate (ORR)(Up to approximately 68 months)
- Duration of response (DOR)(Up to approximately 68 months)
- Progression-free survival (PFS)(Up to approximately 68 months)
- Overall survival (OS)(Up to approximately 68 months)
- Steady state trough concentration (Ctrough,ss) of belzutifan (Cohort 2)(Pre-dose, and 1, 2 and 4 hours postdose)
- Percent change from baseline in erythropoietin (EPO) level(Baseline, up to approximately 6 weeks)
- 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)
- 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)
- 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)