Study of MK-4166 and MK-4166 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4166-001)
12 januari 2021 bijgewerkt door: Merck Sharp & Dohme LLC
Phase 1 Trial of Single Agent MK-4166 and MK-4166 in Combination With Pembrolizumab in Subjects With Advanced Malignancies
This is planned to be a 5-part dose-escalation study to determine the safety and tolerability of MK-4166 monotherapy and MK-4166 plus pembrolizumab combination therapy, and to establish the maximum tolerated dose (MTD) or maximum administered dose (MAD) of MK-4166 and MK-4166 plus pembrolizumab by defining dose-limiting toxicities (DLTs) in participants with advanced solid tumors.
Studie Overzicht
Toestand
Voltooid
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
In Part A, MK-4166 doses will be escalated quickly in successive cohorts and based on safety events may progress to Part B, in which the preliminary MTD will be identified. Based on safety events the study may progress to Part C in which the MTD will be confirmed. In Part D, participants will receive escalating doses of MK-4166 plus a fixed dose of pembrolizumab (MK-3475) 200 mg to determine the MTD for MK-4166 in combination with pembrolizumab. Based on safety events in Part D, the study may progress to Part E in which the MTD for MK-4166 in combination with pembrolizumab will be confirmed.
With Amendments 05/06, the dose confirmation Part C will be removed and the dose confirmation Part E (combination of MK-4166 and pembrolizumab) will be limited to participants with advanced malignant melanoma.
Studietype
Ingrijpend
Inschrijving (Werkelijk)
116
Fase
- Fase 1
Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
18 jaar en ouder (Volwassen, Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Beschrijving
Inclusion criteria:
- Has a histologically- or cytologically-confirmed metastatic solid tumor for which there is no available therapy which may convey clinical benefit. Part E: Has advanced malignant melanoma.
- Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
- Adequate organ function
- Female participants of childbearing potential must have a negative urine or serum pregnancy test and must be surgically sterile or willing to use 2 methods of birth control or abstain from heterosexual activity for the course of the study through 120 days after last dose of study drug
- Male participants must agree to use an adequate method of contraception during sexual contact with females of childbearing potential starting with the first dose of study drug through 180 days after the last dose of study drug
- Submit an evaluable tumor sample for analysis.
Exclusion criteria:
- Chemotherapy, radiation, or biological cancer therapy within 4 weeks prior to the first dose of study drug, or who has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from the adverse events due to cancer therapeutics administered more than 4 weeks earlier
- Currently participating or has participated in a study of an investigational agent or using an investigational device within 28 days of administration of MK-4166
- Expected to require any other form of antineoplastic therapy while on study
- On chronic systemic steroid therapy in excess of replacement doses, or on any other form of immunosuppressive medication
- History of a malignancy for which potentially curative treatment has been completed, with no evidence of malignancy for 5 years excepting successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, or in situ cervical cancer
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Severe hypersensitivity reaction to treatment with another monoclonal antibody
- Active autoimmune disease or a documented history of autoimmune disease, except vitiligo or resolved childhood asthma/atopy
- Active infection requiring therapy
- Current pneumonitis, or a history of (non-infectious) pneumonitis that required steroids
- Prior stem cell or bone marrow transplant
- Positive for human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Regular user (including "recreational use") of any illicit drugs or recent history (within the last year) of substance abuse (including alcohol)
- Symptomatic ascites or pleural effusion
- Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study
- Clinically significant heart disease
- Major surgery in the past 16 weeks
- Received a live vaccine within 30 days prior to first dose of study drug
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Niet-gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: MK-4166 0.0015 mg
Participant received 0.0015 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
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Experimenteel: MK-4166 0.0045 mg
Participant received 0.0045 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
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Experimenteel: MK-4166 0.014 mg
Participant received 0.014 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
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Experimenteel: MK-4166 0.04 mg
Participant received 0.04 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
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Experimenteel: MK-4166 0.12 mg
Participant received 0.12 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
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Experimenteel: MK-4166 0.37 mg
Participant received 0.37 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
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Experimenteel: MK-4166 1.1 mg
Participant received 1.1 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
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Experimenteel: MK-4166 3.3 mg
Participant received 3.3 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
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Experimenteel: MK-4166 10 mg
Participant received 10 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
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Experimenteel: MK-4166 30 mg
Participants received 30 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
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Experimenteel: MK-4166 42 mg
Participants received 42 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
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Experimenteel: MK-4166 59 mg
Participants received 59 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
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Experimenteel: MK-4166 82 mg
Participants received 82 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
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Experimenteel: MK-4166 120 mg
Participants received 120 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
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Experimenteel: MK-4166 170 mg
Participants received 170 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
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Experimenteel: MK-4166 240 mg
Participants received 240 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
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Experimenteel: MK-4166 340 mg
Participants received 340 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
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Experimenteel: MK-4166 480 mg
Participants received 480 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
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Experimenteel: MK-4166 670 mg
Participants received 670 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
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Experimenteel: MK-4166 900 mg
Participants received 900 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
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Experimenteel: MK-4166 1.1 mg + Pembro
Participants received 1.1 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.
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Experimenteel: MK-4166 3.3 mg + Pembro
Participants received 3.3 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.
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Experimenteel: MK-4166 10 mg + Pembro
Participants received 10 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.
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Experimenteel: MK-4166 30 mg + Pembro
Participants received 30 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.
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Experimenteel: MK-4166 42 mg + Pembro
Participants received 42 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.
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Experimenteel: MK-4166 59 mg + Pembro
Participants received 59 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.
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Experimenteel: MK-4166 82 mg + Pembro
Participants received 82 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.
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Experimenteel: MK-4166 120 mg + Pembro
Participants received 120 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.
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Experimenteel: MK-4166 170 mg + Pembro
Participants received 170 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.
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Experimenteel: MK-4166 240 mg + Pembro
Participants received 240 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.
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Experimenteel: MK-4166 340 mg + Pembro
Participants received 340 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.
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Experimenteel: MK-4166 480 mg + Pembro
Participants received 480 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.
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Experimenteel: MK-4166 670 mg + Pembro
Participants received 670 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.
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Experimenteel: MK-4166 900 mg + Pembro
Participants received 900 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles plus pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
Tijdsspanne: Cycle 1 (up to 21 days)
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DLT's were assessed during the first cycle (21 days) for each dose level and included the following if assessed by the Investigator to be possibly, probably or definitely related to MK-4166 or MK-4166 plus pembrolizumab combination: Grade 4 non-hematologic toxicity; Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia (Grade 4 thrombocytopenia of any duration or Grade 3 thrombocytopenia if associated with bleeding); Grade 3 non-hematologic toxicity lasting >3 days despite optimal supportive care; Grade 3 nausea, vomiting or diarrhea if >3 days despite optimal supportive care; any Grade 3 or Grade 4 non-hematologic laboratory abnormality if medical intervention is required or if leading to hospitalization or if persisting for >1 week; febrile neutropenia Grade 3 or Grade 4; any drug-related AE which caused participant to discontinue treatment during Cycle 1; Grade 5 toxicity; any treatment-related toxicity which caused a >2 week delay in initiation of Cycle 2.
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Cycle 1 (up to 21 days)
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Number of Participants Experiencing Adverse Events (AEs)
Tijdsspanne: From first dose up to 90 days post last dose (up to 27 months)
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An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable 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 (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. Per protocol, the number of participants experiencing an AE was assessed and reported by arm (MK-4166 monotherapy and MK-4166 plus pembrolizumab combination therapy) as well as by dose cohort. |
From first dose up to 90 days post last dose (up to 27 months)
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Number of Participants Discontinuing Study Treatment Due to AEs
Tijdsspanne: Up to approximately 24 months
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An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable 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 (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. Per protocol, the number of participants discontinuing study treatment due to AEs was assessed and reported by arm (MK-4166 monotherapy and MK-4166 plus pembrolizumab combination therapy) as well as by dose cohort. |
Up to approximately 24 months
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Maximum Concentration (Cmax) of MK-4166 Over Time
Tijdsspanne: Cycles 1-4: Day 1 pre-dose, at end of MK-4166 infusion (up to 10 minutes), 2 hours; Days 2, 3, 5 (Cohorts 1-9 only), 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Blood samples were collected at pre-specified time points during Cycles 1-4 and plasma isolated for analysis of MK-4166 Cmax.
Cmax was defined as the maximum concentration of MK-4166 reached.
MK-4166 Cmax was reported by dose cohort.
Per protocol, percent geometric coefficient of variation (%GCV) values were not reported for cohorts with n<2 participants.
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Cycles 1-4: Day 1 pre-dose, at end of MK-4166 infusion (up to 10 minutes), 2 hours; Days 2, 3, 5 (Cohorts 1-9 only), 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Time to Maximum Concentration (Tmax) of MK-4166 Over Time
Tijdsspanne: Cycles 1-4: Day 1 pre-dose, at end of MK-4166 infusion (up to 10 minutes), 2 hours; Days 2, 3, 5 (Cohorts 1-9 only), 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Blood samples were collected at pre-specified time points during Cycles 1-4 and plasma isolated for analysis of MK-4166 Tmax.
Tmax was defined as time to the maximum concentration of MK-4166 reached.
MK-4166 Tmax was reported by dose cohort.
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Cycles 1-4: Day 1 pre-dose, at end of MK-4166 infusion (up to 10 minutes), 2 hours; Days 2, 3, 5 (Cohorts 1-9 only), 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Terminal Half-Life (t ½) of MK-4166 Over Time
Tijdsspanne: Cycles 1-4: Day 1 pre-dose, at end of MK-4166 infusion (up to 10 minutes), 2 hours; Days 2, 3, 5 (Cohorts 1-9 only), 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Blood samples were collected at pre-specified time points during Cycles 1-4 and plasma isolated for analysis of MK-4166 t½.
t½ was defined as the time required to divide the MK-4166 plasma concentration by two after reaching pseudo-equilibrium, following a single dose of MK-4166.
MK-4166 t½ was reported by dose cohort.
Per protocol, % GCV values were not reported for cohorts with n<2 participants.
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Cycles 1-4: Day 1 pre-dose, at end of MK-4166 infusion (up to 10 minutes), 2 hours; Days 2, 3, 5 (Cohorts 1-9 only), 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time
Tijdsspanne: Cycles 1-4: Day 1 pre-dose, at end of MK-4166 infusion (up to 10 minutes), 2 hours; Day 2. Each cycle was 21 days. (Up to ~3 months)
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Blood samples were collected at pre-specified time points during Cycles 1-4 and plasma isolated for analysis of MK-4166 AUC0-21.
AUC0-21 was defined as the area under the concentration-time curve of MK-4166 from time zero to 21 hours after dosing.
MK-4166 AUC0-21 was reported by dose cohort.
Per protocol, % GCV values were not reported for cohorts with n<2 participants.
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Cycles 1-4: Day 1 pre-dose, at end of MK-4166 infusion (up to 10 minutes), 2 hours; Day 2. Each cycle was 21 days. (Up to ~3 months)
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Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time
Tijdsspanne: Cycles 1-4: Day 1 pre-dose, at end of MK-4166 infusion (up to 10 minutes), 2 hours; Days 2, 3, 5 (Cohorts 1-9 only), 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Blood samples were collected at pre-specified time points during Cycles 1-4 and plasma isolated for analysis of MK-4166 AUC0-last.
AUC0-last was defined as the area under the concentration-time curve of MK-4166 from time zero to the last quantifiable sample.
MK-4166 AUC0-last was reported by dose cohort.
Per protocol, % GCV values were not reported for cohorts with n<2 participants.
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Cycles 1-4: Day 1 pre-dose, at end of MK-4166 infusion (up to 10 minutes), 2 hours; Days 2, 3, 5 (Cohorts 1-9 only), 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time
Tijdsspanne: Cycles 1-4: Day 1 pre-dose, at end of MK-4166 infusion (up to 10 minutes), 2 hours; Days 2, 3, 5 (Cohorts 1-9 only), 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Blood samples were collected at pre-specified time points during Cycles 1-4 and plasma isolated for analysis of MK-4166 AUC0-inf.
AUC0-inf was defined as the area under the concentration-time curve of MK-4166 from time zero to infinity.
MK-4166 AUC0-inf was reported by dose cohort.
Per protocol, % GCV values were not reported for cohorts with n<2 participants.
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Cycles 1-4: Day 1 pre-dose, at end of MK-4166 infusion (up to 10 minutes), 2 hours; Days 2, 3, 5 (Cohorts 1-9 only), 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Apparent Clearance (CL) of MK-4166 Over Time
Tijdsspanne: Cycles 1-4: Day 1 pre-dose, at end of MK-4166 infusion (up to 10 minutes), 2 hours; Days 2, 3, 5 (Cohorts 1-9 only), 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Blood samples were collected at pre-specified time points during Cycles 1-4 and plasma isolated for analysis of MK-4166 CL.
CL was defined as the volume of plasma from which MK-4166 is eliminated per unit time following IV MK-4166 administration.
MK-4166 CL was reported by dose cohort.
Per protocol, % GCV values were not reported for cohorts with n<2 participants.
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Cycles 1-4: Day 1 pre-dose, at end of MK-4166 infusion (up to 10 minutes), 2 hours; Days 2, 3, 5 (Cohorts 1-9 only), 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Apparent Volume of Distribution (V) of MK-4166 Over Time
Tijdsspanne: Cycles 1-4: Day 1 pre-dose, at end of MK-4166 infusion (up to 10 minutes), 2 hours; Days 2, 3, 5 (Cohorts 1-9 only), 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Blood samples were collected at pre-specified time points during Cycles 1-4 and plasma isolated for analysis of MK-4166 V. V was defined as the theoretical volume that would be necessary to contain the total amount of administered MK-4166 at the same concentration that it is observed in the blood plasma.
MK-4166 V was reported by dose cohort.
Per protocol, % GCV values were not reported for cohorts with n<2 participants.
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Cycles 1-4: Day 1 pre-dose, at end of MK-4166 infusion (up to 10 minutes), 2 hours; Days 2, 3, 5 (Cohorts 1-9 only), 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Maximum Concentration (Cmax) of Pembrolizumab Over Time
Tijdsspanne: Cycles 1-4: Day 1 pre-dose, at end of pembro infusion (up to 10 minutes), at end of MK-4166 infusion (up to 10 minutes), ~2 hours after start of MK-4166 infusion, Days 2, 3, 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Blood samples were collected at pre-specified time points during Cycles 1-4 from MK-4166 plus pembrolizumab combination cohorts only and plasma isolated for analysis of pembrolizumab Cmax.
Cmax was defined as the maximum concentration of pembrolizumab reached.
Pembrolizumab Cmax was reported by dose cohort for all participants that received MK-4166 plus pembrolizumab combination therapy.
Per protocol, participants receiving MK-4166 monotherapy were excluded from this analysis.
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Cycles 1-4: Day 1 pre-dose, at end of pembro infusion (up to 10 minutes), at end of MK-4166 infusion (up to 10 minutes), ~2 hours after start of MK-4166 infusion, Days 2, 3, 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time
Tijdsspanne: Cycles 1-4: Day 1 pre-dose, at end of pembro infusion (up to 10 minutes), at end of MK-4166 infusion (up to 10 minutes), ~2 hours after start of MK-4166 infusion, Days 2, 3, 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Blood samples were collected at pre-specified time points during Cycles 1-4 from MK-4166 plus pembrolizumab combination cohorts only and plasma isolated for analysis of pembrolizumab Tmax.
Tmax was defined as time to the maximum concentration of pembrolizumab reached.
Pembrolizumab Tmax was reported by dose cohort for all participants that received MK-4166 plus pembrolizumab combination therapy.
Per protocol, participants receiving MK-4166 monotherapy were excluded from this analysis.
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Cycles 1-4: Day 1 pre-dose, at end of pembro infusion (up to 10 minutes), at end of MK-4166 infusion (up to 10 minutes), ~2 hours after start of MK-4166 infusion, Days 2, 3, 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Terminal Half-Life (t ½) of Pembrolizumab Over Time
Tijdsspanne: Cycles 1-4: Day 1 pre-dose, at end of pembro infusion (up to 10 minutes), at end of MK-4166 infusion (up to 10 minutes), ~2 hours after start of MK-4166 infusion, Days 2, 3, 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Blood samples were collected at pre-specified time points during Cycles 1-4 from MK-4166 plus pembrolizumab combination cohorts only and plasma isolated for analysis of pembrolizumab t½.
t½ was defined as the time required to divide the pembrolizumab plasma concentration by two after reaching pseudo-equilibrium, following a single dose of pembrolizumab.
Pembrolizumab t½ was reported by dose cohort for all participants that received MK-4166 plus pembrolizumab combination therapy.
Per protocol, participants receiving MK-4166 monotherapy were excluded from this analysis.
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Cycles 1-4: Day 1 pre-dose, at end of pembro infusion (up to 10 minutes), at end of MK-4166 infusion (up to 10 minutes), ~2 hours after start of MK-4166 infusion, Days 2, 3, 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time
Tijdsspanne: Cycles 1-4: Day 1 pre-dose, at end of pembro infusion (up to 10 minutes), at end of MK-4166 infusion (up to 10 minutes), ~2 hours after start of MK-4166 infusion, Day 2. Each cycle was 21 days. (Up to ~3 months)
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Blood samples were collected at pre-specified time points during Cycles 1-4 from MK-4166 plus pembrolizumab combination cohorts only and plasma isolated for analysis of pembrolizumab AUC0-21.
AUC0-21 was defined as the area under the concentration-time curve of pembrolizumab from time zero to 21 hours after dosing.
Pembrolizumab AUC0-21 was reported by dose cohort for all participants that received MK-4166 plus pembrolizumab combination therapy.
Per protocol, participants receiving MK-4166 monotherapy were excluded from this analysis.
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Cycles 1-4: Day 1 pre-dose, at end of pembro infusion (up to 10 minutes), at end of MK-4166 infusion (up to 10 minutes), ~2 hours after start of MK-4166 infusion, Day 2. Each cycle was 21 days. (Up to ~3 months)
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Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time
Tijdsspanne: Cycles 1-4: Day 1 pre-dose, at end of pembro infusion (up to 10 minutes), at end of MK-4166 infusion (up to 10 minutes), ~2 hours after start of MK-4166 infusion, Days 2, 3, 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Blood samples were collected at pre-specified time points during Cycles 1-4 from MK-4166 plus pembrolizumab combination cohorts only and plasma isolated for analysis of pembrolizumab AUC0-last.
AUC0-last was defined as the area under the concentration-time curve of pembrolizumab from time zero to the last quantifiable sample.
Pembrolizumab AUC0-last was reported by dose cohort for all participants that received MK-4166 plus pembrolizumab combination therapy.
Per protocol, participants receiving MK-4166 monotherapy were excluded from this analysis.
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Cycles 1-4: Day 1 pre-dose, at end of pembro infusion (up to 10 minutes), at end of MK-4166 infusion (up to 10 minutes), ~2 hours after start of MK-4166 infusion, Days 2, 3, 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time
Tijdsspanne: Cycles 1-4: Day 1 pre-dose, at end of pembro infusion (up to 10 minutes), at end of MK-4166 infusion (up to 10 minutes), ~2 hours after start of MK-4166 infusion, Days 2, 3, 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Blood samples were collected at pre-specified time points during Cycles 1-4 from MK-4166 plus pembrolizumab combination cohorts only and plasma isolated for analysis of pembrolizumab AUC0-inf.
AUC0-inf was defined as the area under the concentration-time curve of pembrolizumab from time zero to infinity.
Pembrolizumab AUC0-inf was reported by dose cohort for all participants that received MK-4166 plus pembrolizumab combination therapy.
Per protocol, participants receiving MK-4166 monotherapy were excluded from this analysis.
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Cycles 1-4: Day 1 pre-dose, at end of pembro infusion (up to 10 minutes), at end of MK-4166 infusion (up to 10 minutes), ~2 hours after start of MK-4166 infusion, Days 2, 3, 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Apparent Clearance (CL) of Pembrolizumab Over Time
Tijdsspanne: Cycles 1-4: Day 1 pre-dose, at end of pembro infusion (up to 10 minutes), at end of MK-4166 infusion (up to 10 minutes), ~2 hours after start of MK-4166 infusion, Days 2, 3, 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Blood samples were collected at pre-specified time points during Cycles 1-4 from MK-4166 plus pembrolizumab combination cohorts only and plasma isolated for analysis of pembrolizumab CL.
CL was defined as the volume of plasma from which pembrolizumab is eliminated per unit time following IV pembrolizumab administration.
Pembrolizumab CL was reported by dose cohort for all participants that received MK-4166 plus pembrolizumab combination therapy.
Per protocol, participants receiving MK-4166 monotherapy were excluded from this analysis.
|
Cycles 1-4: Day 1 pre-dose, at end of pembro infusion (up to 10 minutes), at end of MK-4166 infusion (up to 10 minutes), ~2 hours after start of MK-4166 infusion, Days 2, 3, 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Apparent Volume of Distribution (V) of Pembrolizumab Over Time
Tijdsspanne: Cycles 1-4: Day 1 pre-dose, at end of pembro infusion (up to 10 minutes), at end of MK-4166 infusion (up to 10 minutes), ~2 hours after start of MK-4166 infusion, Days 2, 3, 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Blood samples were collected at pre-specified time points during Cycles 1-4 from MK-4166 plus pembrolizumab combination cohorts only and plasma isolated for analysis of pembrolizumab V. V was defined as the theoretical volume that would be necessary to contain the total amount of administered pembrolizumab at the same concentration that it is observed in the blood plasma.
Pembrolizumab V was reported by dose cohort for all participants that received MK-4166 plus pembrolizumab combination therapy.
Per protocol, participants receiving MK-4166 monotherapy were excluded from this analysis.
|
Cycles 1-4: Day 1 pre-dose, at end of pembro infusion (up to 10 minutes), at end of MK-4166 infusion (up to 10 minutes), ~2 hours after start of MK-4166 infusion, Days 2, 3, 8, 15. Each cycle was 21 days. (Up to ~3 months)
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Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration
Tijdsspanne: Cycle 1 Day 1: at end of infusion (up to 10 minutes), 2 hours post-infusion, Cycle 1 Days 2, 3, 5, 8, 15, Cycle 2 Day 1 pre-dose. Each cycle was 21 days.
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GITR protein receptor is internalized upon binding by MK-4166.
To evaluate GITR target engagement, a GITR receptor availability assay was developed to assess the availability of cell surface GITR following administration of MK-4166.
GITR was detected on CD4+CD25+ and CD4+CD95+ T-cell sub-populations in peripheral blood using flow cytometry.
GITR receptor availability on representative CD4+ CD25+ T cell subsets following MK-4166 administration was reported over time for each dose cohort.
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Cycle 1 Day 1: at end of infusion (up to 10 minutes), 2 hours post-infusion, Cycle 1 Days 2, 3, 5, 8, 15, Cycle 2 Day 1 pre-dose. Each cycle was 21 days.
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Publicaties en nuttige links
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Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start (Werkelijk)
27 juni 2014
Primaire voltooiing (Werkelijk)
31 juli 2019
Studie voltooiing (Werkelijk)
31 juli 2019
Studieregistratiedata
Eerst ingediend
5 mei 2014
Eerst ingediend dat voldeed aan de QC-criteria
5 mei 2014
Eerst geplaatst (Schatting)
7 mei 2014
Updates van studierecords
Laatste update geplaatst (Werkelijk)
28 januari 2021
Laatste update ingediend die voldeed aan QC-criteria
12 januari 2021
Laatst geverifieerd
1 januari 2021
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- 4166-001
- MK-4166-001 (Andere identificatie: Merck)
Plan Individuele Deelnemersgegevens (IPD)
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JA
Beschrijving IPD-plan
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .
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