Belzutifan
Drug40 mg tablet administered orally at a dose of 120 mg
Other names: MK-6482, PT2977
NCT Number: NCT05030506
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.
This study is active but is not currently recruiting participants.
Notify Me18 year and older
All sexes
Interventional
Phase 1
Beijing Cancer hospital-Digestive Oncology ( Site 0001), Beijing, Beijing Municipality, China
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Male Participants:
Female Participants:
For Belzutifan + Lenvatinib treatment:
For Belzutifan + Lenvatinib + Pembrolizumab treatment:
Exclusion criteria
For Belzutifan + Lenvatinib + Pembrolizumab treatment:
40 mg tablet administered orally at a dose of 120 mg
Other names: MK-6482, PT2977
25 mg/mL solution for Infusion in a single-dose vial administered intravenously at a dose of 400 mg
Other names: MK-3475 KEYTRUDA®
10 mg capsule administered orally at a dose of 20 mg
Other names: MK-7902, E7080, LENVIMA®
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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 frame: 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.
Time frame: 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.
Time frame: 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 frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to approximately 68 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.
Time frame: Up to approximately 68 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.
Time frame: Up to approximately 68 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.
Time frame: Up to approximately 68 months
OS, defined as the time from first dose of study treatment to death due to any cause, will be presented.
Time frame: 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.
Time frame: Baseline, up to approximately 6 weeks
Percent change from baseline in EPO level will be measured and presented.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Merck Sharp & Dohme LLC
Industry
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
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
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