Solid Tumor
Conditions
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALMK-4166
BIOLOGICALPembrolizumab
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | Cycle 1 (up to 21 days) | 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. |
| Number of Participants Experiencing Adverse Events (AEs) | From first dose up to 90 days post last dose (up to 27 months) | 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. |
| Number of Participants Discontinuing Study Treatment Due to AEs | Up to approximately 24 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | 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) | 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. |
| Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | 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) | 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. |
| Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | 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) | 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. |
| Apparent Clearance (CL) of MK-4166 Over Time | 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) | 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. |
| Apparent Volume of Distribution (V) of MK-4166 Over Time | 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) | 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. |
| Maximum Concentration (Cmax) of Pembrolizumab Over Time | 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) | 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. |
| Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | 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) | 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. |
| Maximum Concentration (Cmax) of MK-4166 Over Time | 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) | 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. |
| Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | 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) | 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. |
| Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | 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) | 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. |
| Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | 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) | 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. |
| Apparent Clearance (CL) of Pembrolizumab Over Time | 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) | 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. |
| Apparent Volume of Distribution (V) of Pembrolizumab Over Time | 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) | 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. |
| Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | 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. | 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. |
| Terminal Half-Life (t ½) of Pembrolizumab Over Time | 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) | 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. |
| Time to Maximum Concentration (Tmax) of MK-4166 Over Time | 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) | 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. |
| Terminal Half-Life (t ½) of MK-4166 Over Time | 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) | 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. |
Participant flow
Pre-assignment details
Of 116 participants that were non-randomly allocated to treatment, 113 participants received treatment and were evaluable for all analyses.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 1 |
| 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. | 1 |
| 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. | 1 |
| 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. | 1 |
| 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. | 1 |
| 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. | 1 |
| 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. | 1 |
| 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. | 1 |
| MK-4166 10 mg Participant received 10 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles. | 1 |
| MK-4166 30 mg Participants received 30 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles. | 6 |
| MK-4166 42 mg Participants received 42 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles. | 3 |
| MK-4166 59 mg Participants received 59 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles. | 3 |
| MK-4166 82 mg Participants received 82 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles. | 4 |
| MK-4166 120 mg Participants received 120 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles. | 3 |
| MK-4166 170 mg Participants received 170 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles. | 3 |
| MK-4166 240 mg Participants received 240 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles. | 5 |
| MK-4166 340 mg Participants received 340 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles. | 4 |
| MK-4166 480 mg Participants received 480 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles. | 3 |
| MK-4166 670 mg Participants received 670 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles. | 3 |
| MK-4166 900 mg Participants received 900 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles. | 4 |
| 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. | 3 |
| 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. | 5 |
| 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. | 3 |
| 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. | 3 |
| 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. | 3 |
| 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. | 3 |
| 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. | 4 |
| 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. | 3 |
| 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. | 3 |
| 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. | 3 |
| 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. | 3 |
| 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. | 3 |
| 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. | 4 |
| 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. | 23 |
| Total | 116 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 | FG019 | FG020 | FG021 | FG022 | FG023 | FG024 | FG025 | FG026 | FG027 | FG028 | FG029 | FG030 | FG031 | FG032 | FG033 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 1 |
| Overall Study | Clinical Progression | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 2 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Excluded Medication | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 3 |
| Overall Study | Progressive Disease | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 3 | 3 | 2 | 2 | 3 | 2 | 1 | 2 | 1 | 3 | 1 | 1 | 3 | 2 | 3 | 0 | 1 | 2 | 1 | 2 | 3 | 1 | 1 | 3 | 6 |
| Overall Study | Screen Failure | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Transferred to Extension Study | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 2 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | MK-4166 0.0015 mg | MK-4166 0.0045 mg | MK-4166 0.014 mg | MK-4166 0.04 mg | MK-4166 0.12 mg | MK-4166 0.37 mg | MK-4166 1.1 mg | MK-4166 3.3 mg | MK-4166 10 mg | MK-4166 30 mg | MK-4166 42 mg | MK-4166 59 mg | MK-4166 82 mg | MK-4166 120 mg | MK-4166 170 mg | MK-4166 240 mg | MK-4166 340 mg | MK-4166 480 mg | MK-4166 670 mg | MK-4166 900 mg | MK-4166 1.1 mg + Pembro | MK-4166 3.3 mg + Pembro | MK-4166 10 mg + Pembro | MK-4166 30 mg + Pembro | MK-4166 42 mg + Pembro | MK-4166 59 mg + Pembro | MK-4166 82 mg + Pembro | MK-4166 120 mg + Pembro | MK-4166 170 mg + Pembro | MK-4166 240 mg + Pembro | MK-4166 340 mg + Pembro | MK-4166 480 mg + Pembro | MK-4166 670 mg + Pembro | MK-4166 900 mg + Pembro | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 45.0 Years STANDARD_DEVIATION 0 | 50.0 Years STANDARD_DEVIATION 0 | 43.0 Years STANDARD_DEVIATION 0 | 47.0 Years STANDARD_DEVIATION 0 | 74.0 Years STANDARD_DEVIATION 0 | 65.0 Years STANDARD_DEVIATION 0 | 72.0 Years STANDARD_DEVIATION 0 | 73.0 Years STANDARD_DEVIATION 0 | 50.0 Years STANDARD_DEVIATION 0 | 64.7 Years STANDARD_DEVIATION 9.3 | 57.3 Years STANDARD_DEVIATION 7.1 | 54.3 Years STANDARD_DEVIATION 12.6 | 66.8 Years STANDARD_DEVIATION 22.5 | 61.7 Years STANDARD_DEVIATION 4.2 | 62.0 Years STANDARD_DEVIATION 11.8 | 64.6 Years STANDARD_DEVIATION 11.7 | 66.0 Years STANDARD_DEVIATION 9.7 | 66.7 Years STANDARD_DEVIATION 12.1 | 64.0 Years STANDARD_DEVIATION 12.2 | 71.8 Years STANDARD_DEVIATION 9.3 | 60.3 Years STANDARD_DEVIATION 7 | 52.2 Years STANDARD_DEVIATION 17.2 | 58.0 Years STANDARD_DEVIATION 11.4 | 48.3 Years STANDARD_DEVIATION 25.5 | 52.3 Years STANDARD_DEVIATION 3.8 | 74.0 Years STANDARD_DEVIATION 6.2 | 49.0 Years STANDARD_DEVIATION 23.2 | 56.3 Years STANDARD_DEVIATION 11.2 | 63.0 Years STANDARD_DEVIATION 9.8 | 49.7 Years STANDARD_DEVIATION 25.1 | 52.7 Years STANDARD_DEVIATION 17.6 | 63.3 Years STANDARD_DEVIATION 24.7 | 60.5 Years STANDARD_DEVIATION 20.5 | 62.0 Years STANDARD_DEVIATION 15.6 | 60.4 Years STANDARD_DEVIATION 14.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 6 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 5 Participants | 4 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 5 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 23 Participants | 116 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 6 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 5 Participants | 4 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 5 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 23 Participants | 116 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 3 Participants | 3 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 6 Participants | 58 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 4 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 4 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 3 Participants | 17 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk | EG021 affected / at risk | EG022 affected / at risk | EG023 affected / at risk | EG024 affected / at risk | EG025 affected / at risk | EG026 affected / at risk | EG027 affected / at risk | EG028 affected / at risk | EG029 affected / at risk | EG030 affected / at risk | EG031 affected / at risk | EG032 affected / at risk | EG033 affected / at risk | EG034 affected / at risk | EG035 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 16 / 50 | 13 / 66 | 0 / 1 | 1 / 1 | 1 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 1 / 1 | 0 / 1 | 3 / 6 | 0 / 3 | 1 / 3 | 0 / 4 | 1 / 3 | 1 / 3 | 2 / 5 | 1 / 4 | 1 / 3 | 1 / 3 | 2 / 4 | 0 / 3 | 1 / 5 | 1 / 3 | 0 / 3 | 0 / 3 | 2 / 3 | 2 / 4 | 0 / 3 | 0 / 3 | 0 / 3 | 1 / 3 | 1 / 3 | 2 / 4 | 3 / 23 |
| other Total, other adverse events | 43 / 48 | 63 / 65 | 0 / 1 | 1 / 1 | 1 / 1 | 1 / 1 | 1 / 1 | 1 / 1 | 1 / 1 | 1 / 1 | 1 / 1 | 4 / 6 | 3 / 3 | 3 / 3 | 2 / 3 | 2 / 3 | 3 / 3 | 5 / 5 | 4 / 4 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 4 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 4 / 4 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 4 / 4 | 22 / 23 |
| serious Total, serious adverse events | 6 / 48 | 21 / 65 | 0 / 1 | 1 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 2 / 6 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 5 | 1 / 4 | 2 / 3 | 0 / 3 | 0 / 3 | 1 / 3 | 1 / 4 | 1 / 3 | 0 / 3 | 2 / 3 | 3 / 3 | 1 / 4 | 0 / 3 | 0 / 3 | 1 / 3 | 1 / 3 | 1 / 3 | 2 / 4 | 7 / 23 |
Outcome results
Primary
Number of Participants Discontinuing Study Treatment Due to AEs
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.
Time frame: Up to approximately 24 months
Population: All allocated participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-4166 0.0015 mg | Number of Participants Discontinuing Study Treatment Due to AEs | 2 Participants |
| MK-4166 0.0045 mg | Number of Participants Discontinuing Study Treatment Due to AEs | 8 Participants |
| MK-4166 0.014 mg | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 0.04 mg | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 0.12 mg | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 0.37 mg | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 1.1 mg | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 3.3 mg | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 10 mg | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 30 mg | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 42 mg | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 59 mg | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 82 mg | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 120 mg | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 170 mg | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 240 mg | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 340 mg | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 480 mg | Number of Participants Discontinuing Study Treatment Due to AEs | 1 Participants |
| MK-4166 670 mg | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 900 mg | Number of Participants Discontinuing Study Treatment Due to AEs | 1 Participants |
| MK-4166 1.1 mg + Pembro | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 3.3 mg + Pembro | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 10 mg + Pembro | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 30 mg + Pembro | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 42 mg + Pembro | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 59 mg + Pembro | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 82 mg + Pembro | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 120 mg + Pembro | Number of Participants Discontinuing Study Treatment Due to AEs | 1 Participants |
| MK-4166 170 mg + Pembro | Number of Participants Discontinuing Study Treatment Due to AEs | 1 Participants |
| MK-4166 240 mg + Pembro | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 340 mg + Pembro | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 480 mg + Pembro | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 670 mg + Pembro | Number of Participants Discontinuing Study Treatment Due to AEs | 1 Participants |
| MK-4166 900 mg + Pembro | Number of Participants Discontinuing Study Treatment Due to AEs | 0 Participants |
| MK-4166 670 mg + Pembro | Number of Participants Discontinuing Study Treatment Due to AEs | 1 Participants |
| MK-4166 900 mg + Pembro | Number of Participants Discontinuing Study Treatment Due to AEs | 4 Participants |
Primary
Number of Participants Experiencing Adverse Events (AEs)
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.
Time frame: From first dose up to 90 days post last dose (up to 27 months)
Population: All allocated participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-4166 0.0015 mg | Number of Participants Experiencing Adverse Events (AEs) | 44 Participants |
| MK-4166 0.0045 mg | Number of Participants Experiencing Adverse Events (AEs) | 63 Participants |
| MK-4166 0.014 mg | Number of Participants Experiencing Adverse Events (AEs) | 0 Participants |
| MK-4166 0.04 mg | Number of Participants Experiencing Adverse Events (AEs) | 1 Participants |
| MK-4166 0.12 mg | Number of Participants Experiencing Adverse Events (AEs) | 1 Participants |
| MK-4166 0.37 mg | Number of Participants Experiencing Adverse Events (AEs) | 1 Participants |
| MK-4166 1.1 mg | Number of Participants Experiencing Adverse Events (AEs) | 1 Participants |
| MK-4166 3.3 mg | Number of Participants Experiencing Adverse Events (AEs) | 1 Participants |
| MK-4166 10 mg | Number of Participants Experiencing Adverse Events (AEs) | 1 Participants |
| MK-4166 30 mg | Number of Participants Experiencing Adverse Events (AEs) | 1 Participants |
| MK-4166 42 mg | Number of Participants Experiencing Adverse Events (AEs) | 1 Participants |
| MK-4166 59 mg | Number of Participants Experiencing Adverse Events (AEs) | 5 Participants |
| MK-4166 82 mg | Number of Participants Experiencing Adverse Events (AEs) | 3 Participants |
| MK-4166 120 mg | Number of Participants Experiencing Adverse Events (AEs) | 3 Participants |
| MK-4166 170 mg | Number of Participants Experiencing Adverse Events (AEs) | 2 Participants |
| MK-4166 240 mg | Number of Participants Experiencing Adverse Events (AEs) | 2 Participants |
| MK-4166 340 mg | Number of Participants Experiencing Adverse Events (AEs) | 3 Participants |
| MK-4166 480 mg | Number of Participants Experiencing Adverse Events (AEs) | 5 Participants |
| MK-4166 670 mg | Number of Participants Experiencing Adverse Events (AEs) | 4 Participants |
| MK-4166 900 mg | Number of Participants Experiencing Adverse Events (AEs) | 3 Participants |
| MK-4166 1.1 mg + Pembro | Number of Participants Experiencing Adverse Events (AEs) | 3 Participants |
| MK-4166 3.3 mg + Pembro | Number of Participants Experiencing Adverse Events (AEs) | 3 Participants |
| MK-4166 10 mg + Pembro | Number of Participants Experiencing Adverse Events (AEs) | 3 Participants |
| MK-4166 30 mg + Pembro | Number of Participants Experiencing Adverse Events (AEs) | 3 Participants |
| MK-4166 42 mg + Pembro | Number of Participants Experiencing Adverse Events (AEs) | 3 Participants |
| MK-4166 59 mg + Pembro | Number of Participants Experiencing Adverse Events (AEs) | 3 Participants |
| MK-4166 82 mg + Pembro | Number of Participants Experiencing Adverse Events (AEs) | 3 Participants |
| MK-4166 120 mg + Pembro | Number of Participants Experiencing Adverse Events (AEs) | 3 Participants |
| MK-4166 170 mg + Pembro | Number of Participants Experiencing Adverse Events (AEs) | 4 Participants |
| MK-4166 240 mg + Pembro | Number of Participants Experiencing Adverse Events (AEs) | 3 Participants |
| MK-4166 340 mg + Pembro | Number of Participants Experiencing Adverse Events (AEs) | 3 Participants |
| MK-4166 480 mg + Pembro | Number of Participants Experiencing Adverse Events (AEs) | 3 Participants |
| MK-4166 670 mg + Pembro | Number of Participants Experiencing Adverse Events (AEs) | 3 Participants |
| MK-4166 900 mg + Pembro | Number of Participants Experiencing Adverse Events (AEs) | 3 Participants |
| MK-4166 670 mg + Pembro | Number of Participants Experiencing Adverse Events (AEs) | 4 Participants |
| MK-4166 900 mg + Pembro | Number of Participants Experiencing Adverse Events (AEs) | 22 Participants |
Primary
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
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.
Time frame: Cycle 1 (up to 21 days)
Population: All allocated participants who received at least 1 dose of study treatment and were evaluable for DLTs in Cycle 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-4166 0.0015 mg | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 0.0045 mg | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 0.014 mg | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 0.04 mg | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 0.12 mg | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 0.37 mg | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 1.1 mg | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 3.3 mg | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 10 mg | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 30 mg | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 1 Participants |
| MK-4166 42 mg | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 59 mg | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 82 mg | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 120 mg | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 170 mg | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 240 mg | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 340 mg | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 480 mg | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 670 mg | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 900 mg | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 1.1 mg + Pembro | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 3.3 mg + Pembro | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 10 mg + Pembro | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 30 mg + Pembro | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 42 mg + Pembro | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 59 mg + Pembro | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 82 mg + Pembro | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 120 mg + Pembro | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 170 mg + Pembro | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 240 mg + Pembro | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 340 mg + Pembro | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 480 mg + Pembro | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 670 mg + Pembro | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
| MK-4166 900 mg + Pembro | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | 0 Participants |
Secondary
Apparent Clearance (CL) of MK-4166 Over Time
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.
Time frame: 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)
Population: All allocated participants who received at least 1 dose of MK-4166 and had evaluable CL samples. Per protocol, %GCV values were not reported for cohorts with n\<2 participants. Participants with samples that were hemolyzed or analyzed outside of stability were excluded from the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-4166 0.0015 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 10.6 Liters (L)/day | — |
| MK-4166 0.0015 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 1.68 Liters (L)/day | — |
| MK-4166 0.0015 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 1.38 Liters (L)/day | — |
| MK-4166 0.0045 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 1.15 Liters (L)/day | — |
| MK-4166 0.014 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.565 Liters (L)/day | — |
| MK-4166 0.04 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 1.02 Liters (L)/day | — |
| MK-4166 0.04 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.319 Liters (L)/day | — |
| MK-4166 0.12 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 1.02 Liters (L)/day | — |
| MK-4166 0.12 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 1.73 Liters (L)/day | — |
| MK-4166 0.12 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.887 Liters (L)/day | — |
| MK-4166 0.37 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.550 Liters (L)/day | — |
| MK-4166 0.37 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.142 Liters (L)/day | — |
| MK-4166 1.1 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.344 Liters (L)/day | — |
| MK-4166 3.3 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.392 Liters (L)/day | — |
| MK-4166 3.3 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.940 Liters (L)/day | — |
| MK-4166 10 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.341 Liters (L)/day | — |
| MK-4166 10 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | NA Liters (L)/day | — |
| MK-4166 10 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | NA Liters (L)/day | — |
| MK-4166 30 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.286 Liters (L)/day | Geometric Coefficient of Variation 54 |
| MK-4166 30 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.617 Liters (L)/day | Geometric Coefficient of Variation 226.2 |
| MK-4166 30 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 1.73 Liters (L)/day | Geometric Coefficient of Variation 711.2 |
| MK-4166 42 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.754 Liters (L)/day | Geometric Coefficient of Variation 733.9 |
| MK-4166 42 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.299 Liters (L)/day | Geometric Coefficient of Variation 55.5 |
| MK-4166 42 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.811 Liters (L)/day | Geometric Coefficient of Variation 660.7 |
| MK-4166 42 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 4 | 2.27 Liters (L)/day | Geometric Coefficient of Variation 8160 |
| MK-4166 59 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 4 | 0.236 Liters (L)/day | — |
| MK-4166 59 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.400 Liters (L)/day | Geometric Coefficient of Variation 37.7 |
| MK-4166 59 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.251 Liters (L)/day | — |
| MK-4166 59 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 4.06 Liters (L)/day | Geometric Coefficient of Variation 19927 |
| MK-4166 82 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.246 Liters (L)/day | Geometric Coefficient of Variation 59.5 |
| MK-4166 82 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.301 Liters (L)/day | Geometric Coefficient of Variation 50.1 |
| MK-4166 82 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.378 Liters (L)/day | Geometric Coefficient of Variation 87 |
| MK-4166 82 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 4 | 1.02 Liters (L)/day | Geometric Coefficient of Variation 247.9 |
| MK-4166 120 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 4 | NA Liters (L)/day | — |
| MK-4166 120 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.392 Liters (L)/day | Geometric Coefficient of Variation 32.2 |
| MK-4166 120 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.538 Liters (L)/day | Geometric Coefficient of Variation 45.6 |
| MK-4166 120 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.348 Liters (L)/day | Geometric Coefficient of Variation 54.4 |
| MK-4166 170 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.982 Liters (L)/day | Geometric Coefficient of Variation 658.5 |
| MK-4166 170 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.305 Liters (L)/day | Geometric Coefficient of Variation 31.1 |
| MK-4166 170 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.424 Liters (L)/day | Geometric Coefficient of Variation 55.9 |
| MK-4166 170 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 4 | 0.338 Liters (L)/day | Geometric Coefficient of Variation 133.9 |
| MK-4166 240 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.479 Liters (L)/day | Geometric Coefficient of Variation 51.5 |
| MK-4166 240 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.321 Liters (L)/day | Geometric Coefficient of Variation 6.8 |
| MK-4166 240 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 4 | 0.335 Liters (L)/day | Geometric Coefficient of Variation 0.4 |
| MK-4166 240 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.279 Liters (L)/day | Geometric Coefficient of Variation 53.4 |
| MK-4166 340 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.304 Liters (L)/day | Geometric Coefficient of Variation 67.1 |
| MK-4166 340 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.288 Liters (L)/day | Geometric Coefficient of Variation 69.4 |
| MK-4166 340 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.293 Liters (L)/day | Geometric Coefficient of Variation 72.1 |
| MK-4166 340 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 4 | 0.241 Liters (L)/day | — |
| MK-4166 480 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.302 Liters (L)/day | Geometric Coefficient of Variation 33.3 |
| MK-4166 480 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.320 Liters (L)/day | Geometric Coefficient of Variation 17.2 |
| MK-4166 480 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.349 Liters (L)/day | — |
| MK-4166 670 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.321 Liters (L)/day | Geometric Coefficient of Variation 19.8 |
| MK-4166 670 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.280 Liters (L)/day | — |
| MK-4166 670 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 4 | 0.477 Liters (L)/day | — |
| MK-4166 670 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.259 Liters (L)/day | Geometric Coefficient of Variation 9.9 |
| MK-4166 900 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.199 Liters (L)/day | Geometric Coefficient of Variation 19.2 |
| MK-4166 900 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.166 Liters (L)/day | Geometric Coefficient of Variation 4 |
| MK-4166 900 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.197 Liters (L)/day | Geometric Coefficient of Variation 21.1 |
| MK-4166 900 mg | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 4 | NA Liters (L)/day | — |
| MK-4166 1.1 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 4 | NA Liters (L)/day | — |
| MK-4166 1.1 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.98 Liters (L)/day | Geometric Coefficient of Variation 120.6 |
| MK-4166 1.1 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.987 Liters (L)/day | Geometric Coefficient of Variation 104.1 |
| MK-4166 1.1 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.142 Liters (L)/day | Geometric Coefficient of Variation 32.8 |
| MK-4166 3.3 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.0973 Liters (L)/day | Geometric Coefficient of Variation 8.86 |
| MK-4166 3.3 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.450 Liters (L)/day | Geometric Coefficient of Variation 150.8 |
| MK-4166 3.3 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.161 Liters (L)/day | Geometric Coefficient of Variation 89.4 |
| MK-4166 10 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 4 | 0.124 Liters (L)/day | — |
| MK-4166 10 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 1.57 Liters (L)/day | Geometric Coefficient of Variation 503154.6 |
| MK-4166 10 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.126 Liters (L)/day | — |
| MK-4166 10 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.249 Liters (L)/day | Geometric Coefficient of Variation 122 |
| MK-4166 30 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.150 Liters (L)/day | Geometric Coefficient of Variation 74.4 |
| MK-4166 30 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 4 | 0.282 Liters (L)/day | Geometric Coefficient of Variation 136.8 |
| MK-4166 30 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.165 Liters (L)/day | Geometric Coefficient of Variation 81.4 |
| MK-4166 30 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.182 Liters (L)/day | Geometric Coefficient of Variation 60.1 |
| MK-4166 42 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.341 Liters (L)/day | Geometric Coefficient of Variation 156.1 |
| MK-4166 42 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.296 Liters (L)/day | Geometric Coefficient of Variation 90.1 |
| MK-4166 42 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.362 Liters (L)/day | Geometric Coefficient of Variation 121.4 |
| MK-4166 42 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 4 | 0.119 Liters (L)/day | — |
| MK-4166 59 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 4 | 0.398 Liters (L)/day | Geometric Coefficient of Variation 24.9 |
| MK-4166 59 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.388 Liters (L)/day | Geometric Coefficient of Variation 11.5 |
| MK-4166 59 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.315 Liters (L)/day | Geometric Coefficient of Variation 46 |
| MK-4166 59 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.273 Liters (L)/day | Geometric Coefficient of Variation 32.4 |
| MK-4166 82 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.294 Liters (L)/day | Geometric Coefficient of Variation 37.1 |
| MK-4166 82 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.244 Liters (L)/day | Geometric Coefficient of Variation 23.4 |
| MK-4166 82 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.273 Liters (L)/day | Geometric Coefficient of Variation 27.7 |
| MK-4166 120 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.364 Liters (L)/day | Geometric Coefficient of Variation 79.3 |
| MK-4166 120 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.302 Liters (L)/day | Geometric Coefficient of Variation 51.3 |
| MK-4166 120 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 4 | 0.305 Liters (L)/day | Geometric Coefficient of Variation 66 |
| MK-4166 120 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.430 Liters (L)/day | Geometric Coefficient of Variation 84.3 |
| MK-4166 170 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 4 | 0.296 Liters (L)/day | — |
| MK-4166 170 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.269 Liters (L)/day | Geometric Coefficient of Variation 10.4 |
| MK-4166 170 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.233 Liters (L)/day | Geometric Coefficient of Variation 15.9 |
| MK-4166 170 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.286 Liters (L)/day | Geometric Coefficient of Variation 27.1 |
| MK-4166 240 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.183 Liters (L)/day | Geometric Coefficient of Variation 18.8 |
| MK-4166 240 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.193 Liters (L)/day | Geometric Coefficient of Variation 12.4 |
| MK-4166 240 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 4 | 0.152 Liters (L)/day | Geometric Coefficient of Variation 46.2 |
| MK-4166 240 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.205 Liters (L)/day | Geometric Coefficient of Variation 15.1 |
| MK-4166 340 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.502 Liters (L)/day | Geometric Coefficient of Variation 305.7 |
| MK-4166 340 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.491 Liters (L)/day | Geometric Coefficient of Variation 277.7 |
| MK-4166 340 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 4 | 0.145 Liters (L)/day | — |
| MK-4166 340 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.262 Liters (L)/day | Geometric Coefficient of Variation 52.3 |
| MK-4166 480 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.217 Liters (L)/day | — |
| MK-4166 480 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.230 Liters (L)/day | Geometric Coefficient of Variation 26.2 |
| MK-4166 480 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.272 Liters (L)/day | Geometric Coefficient of Variation 11.9 |
| MK-4166 670 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 4 | 0.176 Liters (L)/day | — |
| MK-4166 670 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.204 Liters (L)/day | Geometric Coefficient of Variation 5.1 |
| MK-4166 670 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.195 Liters (L)/day | Geometric Coefficient of Variation 7.9 |
| MK-4166 670 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.287 Liters (L)/day | Geometric Coefficient of Variation 77 |
| MK-4166 900 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 1 | 0.279 Liters (L)/day | Geometric Coefficient of Variation 40.9 |
| MK-4166 900 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 4 | 0.206 Liters (L)/day | Geometric Coefficient of Variation 33.7 |
| MK-4166 900 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 3 | 0.238 Liters (L)/day | Geometric Coefficient of Variation 28.7 |
| MK-4166 900 mg + Pembro | Apparent Clearance (CL) of MK-4166 Over Time | Cycle 2 | 0.313 Liters (L)/day | Geometric Coefficient of Variation 49 |
Secondary
Apparent Clearance (CL) of Pembrolizumab Over Time
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.
Time frame: 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)
Population: All allocated participants who received ≥1 dose of pembrolizumab and had evaluable CL samples. Per protocol, %GCV values were not reported for cohorts with n\<2 participants, and MK-4166 monotherapy dose cohorts were not analyzed. Participants with samples that were hemolyzed or analyzed outside of stability were excluded from the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-4166 1.1 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 1 | 0.203 L/Day | Geometric Coefficient of Variation 28 |
| MK-4166 1.1 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 3 | 0.219 L/Day | Geometric Coefficient of Variation 53.8 |
| MK-4166 1.1 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 2 | 0.236 L/Day | Geometric Coefficient of Variation 33.5 |
| MK-4166 1.1 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 4 | 0.130 L/Day | — |
| MK-4166 3.3 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 3 | 0.302 L/Day | Geometric Coefficient of Variation 38.5 |
| MK-4166 3.3 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 4 | 0.408 L/Day | — |
| MK-4166 3.3 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 2 | 0.298 L/Day | Geometric Coefficient of Variation 45.4 |
| MK-4166 3.3 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 1 | 0.282 L/Day | Geometric Coefficient of Variation 46.3 |
| MK-4166 10 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 4 | 0.326 L/Day | — |
| MK-4166 10 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 3 | 0.322 L/Day | Geometric Coefficient of Variation 2.3 |
| MK-4166 10 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 1 | 0.309 L/Day | Geometric Coefficient of Variation 11.8 |
| MK-4166 10 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 2 | 0.494 L/Day | Geometric Coefficient of Variation 62.7 |
| MK-4166 30 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 3 | 0.178 L/Day | Geometric Coefficient of Variation 14.1 |
| MK-4166 30 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 2 | 0.210 L/Day | Geometric Coefficient of Variation 12.6 |
| MK-4166 30 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 4 | 0.190 L/Day | Geometric Coefficient of Variation 38.6 |
| MK-4166 30 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 1 | 0.143 L/Day | Geometric Coefficient of Variation 15.6 |
| MK-4166 42 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 4 | 0.146 L/Day | — |
| MK-4166 42 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 3 | 0.316 L/Day | Geometric Coefficient of Variation 59.5 |
| MK-4166 42 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 2 | 0.346 L/Day | Geometric Coefficient of Variation 46.1 |
| MK-4166 42 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 1 | 0.344 L/Day | Geometric Coefficient of Variation 65.7 |
| MK-4166 59 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 3 | 0.216 L/Day | Geometric Coefficient of Variation 8.1 |
| MK-4166 59 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 1 | 0.301 L/Day | Geometric Coefficient of Variation 54.4 |
| MK-4166 59 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 4 | 0.198 L/Day | Geometric Coefficient of Variation 14.7 |
| MK-4166 59 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 2 | 0.230 L/Day | Geometric Coefficient of Variation 16.5 |
| MK-4166 82 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 1 | 0.270 L/Day | Geometric Coefficient of Variation 39 |
| MK-4166 82 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 2 | 0.267 L/Day | Geometric Coefficient of Variation 47.9 |
| MK-4166 82 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 3 | 0.271 L/Day | Geometric Coefficient of Variation 37.4 |
| MK-4166 120 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 3 | 0.222 L/Day | Geometric Coefficient of Variation 50.7 |
| MK-4166 120 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 2 | 0.271 L/Day | Geometric Coefficient of Variation 48.9 |
| MK-4166 120 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 4 | 0.207 L/Day | Geometric Coefficient of Variation 41.9 |
| MK-4166 120 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 1 | 0.255 L/Day | Geometric Coefficient of Variation 37.6 |
| MK-4166 170 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 1 | 0.284 L/Day | Geometric Coefficient of Variation 36 |
| MK-4166 170 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 3 | 0.266 L/Day | Geometric Coefficient of Variation 27.4 |
| MK-4166 170 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 2 | 0.280 L/Day | Geometric Coefficient of Variation 27.9 |
| MK-4166 240 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 1 | 0.184 L/Day | Geometric Coefficient of Variation 22.9 |
| MK-4166 240 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 2 | 0.217 L/Day | Geometric Coefficient of Variation 18.1 |
| MK-4166 240 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 4 | 0.147 L/Day | — |
| MK-4166 240 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 3 | 0.164 L/Day | — |
| MK-4166 340 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 4 | 0.137 L/Day | — |
| MK-4166 340 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 3 | 0.243 L/Day | Geometric Coefficient of Variation 30.1 |
| MK-4166 340 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 2 | 0.242 L/Day | Geometric Coefficient of Variation 20.9 |
| MK-4166 340 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 1 | 0.233 L/Day | Geometric Coefficient of Variation 58.3 |
| MK-4166 480 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 3 | 0.227 L/Day | Geometric Coefficient of Variation 25.5 |
| MK-4166 480 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 2 | 0.202 L/Day | Geometric Coefficient of Variation 14.5 |
| MK-4166 480 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 1 | 0.283 L/Day | Geometric Coefficient of Variation 148.4 |
| MK-4166 670 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 2 | 0.216 L/Day | Geometric Coefficient of Variation 7.5 |
| MK-4166 670 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 3 | 0.207 L/Day | Geometric Coefficient of Variation 6.3 |
| MK-4166 670 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 1 | 0.234 L/Day | Geometric Coefficient of Variation 55.9 |
| MK-4166 670 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 4 | 0.247 L/Day | Geometric Coefficient of Variation 27.7 |
| MK-4166 900 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 4 | 0.224 L/Day | Geometric Coefficient of Variation 59.3 |
| MK-4166 900 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 1 | 0.176 L/Day | Geometric Coefficient of Variation 68.7 |
| MK-4166 900 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 2 | 0.242 L/Day | Geometric Coefficient of Variation 32.1 |
| MK-4166 900 mg + Pembro | Apparent Clearance (CL) of Pembrolizumab Over Time | Cycle 3 | 0.199 L/Day | Geometric Coefficient of Variation 25.2 |
Secondary
Apparent Volume of Distribution (V) of MK-4166 Over Time
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.
Time frame: 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)
Population: All allocated participants who received at least 1 dose of MK-4166 and had evaluable V samples. Per protocol, %GCV values were not reported for cohorts with n\<2 participants. Participants with samples that were hemolyzed or analyzed outside of stability were excluded from the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-4166 0.0015 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | NA Liters | — |
| MK-4166 0.0015 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 5.19 Liters | — |
| MK-4166 0.0015 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 3.58 Liters | — |
| MK-4166 0.0045 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 4.55 Liters | — |
| MK-4166 0.014 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 2.18 Liters | — |
| MK-4166 0.04 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 1.10 Liters | — |
| MK-4166 0.04 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 5.11 Liters | — |
| MK-4166 0.12 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 1.99 Liters | — |
| MK-4166 0.12 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 2.49 Liters | — |
| MK-4166 0.12 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 6.80 Liters | — |
| MK-4166 0.37 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 1.67 Liters | — |
| MK-4166 0.37 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 0.722 Liters | — |
| MK-4166 1.1 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 1.68 Liters | — |
| MK-4166 3.3 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 2.41 Liters | — |
| MK-4166 3.3 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 1.87 Liters | — |
| MK-4166 10 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 3.74 Liters | — |
| MK-4166 10 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | NA Liters | — |
| MK-4166 10 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | NA Liters | — |
| MK-4166 30 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 3.20 Liters | Geometric Coefficient of Variation 32.6 |
| MK-4166 30 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 6.13 Liters | Geometric Coefficient of Variation 84.5 |
| MK-4166 30 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 3.75 Liters | Geometric Coefficient of Variation 27.1 |
| MK-4166 42 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 4 | 3.32 Liters | — |
| MK-4166 42 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 3.23 Liters | Geometric Coefficient of Variation 48.9 |
| MK-4166 42 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 6.59 Liters | Geometric Coefficient of Variation 46.1 |
| MK-4166 42 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 4.76 Liters | Geometric Coefficient of Variation 34.1 |
| MK-4166 59 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 4 | 3.00 Liters | — |
| MK-4166 59 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 1.69 Liters | Geometric Coefficient of Variation 49.7 |
| MK-4166 59 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 3.91 Liters | — |
| MK-4166 59 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 4.15 Liters | — |
| MK-4166 82 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 4.56 Liters | Geometric Coefficient of Variation 35.4 |
| MK-4166 82 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 4 | 4.03 Liters | Geometric Coefficient of Variation 16.5 |
| MK-4166 82 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 3.62 Liters | Geometric Coefficient of Variation 28.9 |
| MK-4166 82 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 4.25 Liters | Geometric Coefficient of Variation 11 |
| MK-4166 120 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 5.14 Liters | Geometric Coefficient of Variation 17.2 |
| MK-4166 120 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 3.19 Liters | Geometric Coefficient of Variation 69.7 |
| MK-4166 120 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 4 | NA Liters | — |
| MK-4166 120 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 4.40 Liters | Geometric Coefficient of Variation 14.9 |
| MK-4166 170 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 5.54 Liters | Geometric Coefficient of Variation 8.6 |
| MK-4166 170 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 3.37 Liters | Geometric Coefficient of Variation 19.3 |
| MK-4166 170 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 5.10 Liters | Geometric Coefficient of Variation 2.5 |
| MK-4166 170 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 4 | 3.55 Liters | Geometric Coefficient of Variation 5 |
| MK-4166 240 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 4 | 3.97 Liters | Geometric Coefficient of Variation 12 |
| MK-4166 240 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 5.25 Liters | Geometric Coefficient of Variation 11.9 |
| MK-4166 240 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 3.57 Liters | Geometric Coefficient of Variation 79.9 |
| MK-4166 240 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 4.41 Liters | Geometric Coefficient of Variation 263 |
| MK-4166 340 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 4.87 Liters | Geometric Coefficient of Variation 83.3 |
| MK-4166 340 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 4 | 6.16 Liters | — |
| MK-4166 340 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 5.44 Liters | Geometric Coefficient of Variation 88.1 |
| MK-4166 340 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 5.27 Liters | Geometric Coefficient of Variation 67.9 |
| MK-4166 480 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 4.42 Liters | Geometric Coefficient of Variation 21.1 |
| MK-4166 480 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 5.53 Liters | — |
| MK-4166 480 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 5.21 Liters | Geometric Coefficient of Variation 34.4 |
| MK-4166 670 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 4 | 2.82 Liters | — |
| MK-4166 670 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 4.24 Liters | — |
| MK-4166 670 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 4.92 Liters | Geometric Coefficient of Variation 48.4 |
| MK-4166 670 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 5.19 Liters | Geometric Coefficient of Variation 75.3 |
| MK-4166 900 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 4.11 Liters | Geometric Coefficient of Variation 63.3 |
| MK-4166 900 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 3.54 Liters | Geometric Coefficient of Variation 17.1 |
| MK-4166 900 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 5.2 Liters | Geometric Coefficient of Variation 61.6 |
| MK-4166 900 mg | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 4 | NA Liters | — |
| MK-4166 1.1 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 5.45 Liters | Geometric Coefficient of Variation 862.6 |
| MK-4166 1.1 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 5.61 Liters | Geometric Coefficient of Variation 3589.3 |
| MK-4166 1.1 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 0.587 Liters | Geometric Coefficient of Variation 30.2 |
| MK-4166 1.1 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 4 | NA Liters | — |
| MK-4166 3.3 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 0.499 Liters | Geometric Coefficient of Variation 111.2 |
| MK-4166 3.3 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 0.844 Liters | Geometric Coefficient of Variation 55.6 |
| MK-4166 3.3 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 0.870 Liters | Geometric Coefficient of Variation 13.1 |
| MK-4166 10 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 2.97 Liters | Geometric Coefficient of Variation 96.8 |
| MK-4166 10 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 2.21 Liters | Geometric Coefficient of Variation 33.9 |
| MK-4166 10 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 3.01 Liters | — |
| MK-4166 10 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 4 | 1.27 Liters | — |
| MK-4166 30 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 4 | 2.71 Liters | Geometric Coefficient of Variation 16.6 |
| MK-4166 30 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 2.5 Liters | Geometric Coefficient of Variation 42.7 |
| MK-4166 30 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 2.76 Liters | Geometric Coefficient of Variation 3.1 |
| MK-4166 30 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 2.61 Liters | Geometric Coefficient of Variation 10.8 |
| MK-4166 42 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 3.12 Liters | Geometric Coefficient of Variation 46.6 |
| MK-4166 42 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 4 | 2.22 Liters | — |
| MK-4166 42 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 3.67 Liters | Geometric Coefficient of Variation 35.8 |
| MK-4166 42 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 3.56 Liters | Geometric Coefficient of Variation 62.3 |
| MK-4166 59 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 2.41 Liters | Geometric Coefficient of Variation 3 |
| MK-4166 59 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 3.91 Liters | Geometric Coefficient of Variation 22.6 |
| MK-4166 59 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 2.90 Liters | Geometric Coefficient of Variation 8.8 |
| MK-4166 59 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 4 | 3.49 Liters | Geometric Coefficient of Variation 32.9 |
| MK-4166 82 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 4.9 Liters | Geometric Coefficient of Variation 40.3 |
| MK-4166 82 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 3.11 Liters | Geometric Coefficient of Variation 28.8 |
| MK-4166 82 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 3.10 Liters | Geometric Coefficient of Variation 39.1 |
| MK-4166 120 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 4.96 Liters | Geometric Coefficient of Variation 69.5 |
| MK-4166 120 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 5.89 Liters | Geometric Coefficient of Variation 18.4 |
| MK-4166 120 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 4 | 5.93 Liters | Geometric Coefficient of Variation 23.7 |
| MK-4166 120 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 4.73 Liters | Geometric Coefficient of Variation 21.2 |
| MK-4166 170 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 4.01 Liters | Geometric Coefficient of Variation 27.1 |
| MK-4166 170 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 4.77 Liters | Geometric Coefficient of Variation 58.9 |
| MK-4166 170 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 4.62 Liters | Geometric Coefficient of Variation 50.2 |
| MK-4166 170 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 4 | 6.29 Liters | — |
| MK-4166 240 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 5.7 Liters | Geometric Coefficient of Variation 25.2 |
| MK-4166 240 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 3.62 Liters | Geometric Coefficient of Variation 14 |
| MK-4166 240 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 4 | 3.61 Liters | Geometric Coefficient of Variation 16.4 |
| MK-4166 240 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 4.58 Liters | Geometric Coefficient of Variation 10.6 |
| MK-4166 340 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 2.95 Liters | Geometric Coefficient of Variation 48.8 |
| MK-4166 340 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 3.97 Liters | Geometric Coefficient of Variation 12.2 |
| MK-4166 340 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 4.36 Liters | Geometric Coefficient of Variation 23.7 |
| MK-4166 340 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 4 | 2.72 Liters | — |
| MK-4166 480 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 4.68 Liters | Geometric Coefficient of Variation 2 |
| MK-4166 480 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 4.44 Liters | Geometric Coefficient of Variation 10.4 |
| MK-4166 480 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 5.41 Liters | — |
| MK-4166 670 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 3.74 Liters | Geometric Coefficient of Variation 1 |
| MK-4166 670 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 4.83 Liters | Geometric Coefficient of Variation 0.5 |
| MK-4166 670 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 4.38 Liters | Geometric Coefficient of Variation 25.2 |
| MK-4166 670 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 4 | 3.04 Liters | — |
| MK-4166 900 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 3 | 7.23 Liters | Geometric Coefficient of Variation 61.1 |
| MK-4166 900 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 2 | 5.94 Liters | Geometric Coefficient of Variation 36.7 |
| MK-4166 900 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 4 | 5.14 Liters | Geometric Coefficient of Variation 37.4 |
| MK-4166 900 mg + Pembro | Apparent Volume of Distribution (V) of MK-4166 Over Time | Cycle 1 | 4.85 Liters | Geometric Coefficient of Variation 38.1 |
Secondary
Apparent Volume of Distribution (V) of Pembrolizumab Over Time
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.
Time frame: 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)
Population: All allocated participants who received ≥1 dose of pembrolizumab and had evaluable V samples. Per protocol, %GCV values were not reported for cohorts with n\<2 participants, and MK-4166 monotherapy dose cohorts were not analyzed. Participants with samples that were hemolyzed or analyzed outside of stability were excluded from the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-4166 1.1 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 1 | 5.03 Liters | Geometric Coefficient of Variation 46.6 |
| MK-4166 1.1 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 4 | 3.10 Liters | — |
| MK-4166 1.1 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 2 | 5.52 Liters | Geometric Coefficient of Variation 17.2 |
| MK-4166 1.1 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 3 | 4.31 Liters | Geometric Coefficient of Variation 10.4 |
| MK-4166 3.3 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 4 | 6.37 Liters | — |
| MK-4166 3.3 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 1 | 4.92 Liters | Geometric Coefficient of Variation 60.7 |
| MK-4166 3.3 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 3 | 4.40 Liters | Geometric Coefficient of Variation 50.6 |
| MK-4166 3.3 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 2 | 8.13 Liters | Geometric Coefficient of Variation 53.3 |
| MK-4166 10 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 3 | 6.81 Liters | Geometric Coefficient of Variation 44.4 |
| MK-4166 10 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 1 | 6.55 Liters | Geometric Coefficient of Variation 21.6 |
| MK-4166 10 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 2 | 7.76 Liters | Geometric Coefficient of Variation 54.5 |
| MK-4166 10 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 4 | 4.92 Liters | — |
| MK-4166 30 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 3 | 3.94 Liters | Geometric Coefficient of Variation 39.5 |
| MK-4166 30 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 1 | 4.85 Liters | Geometric Coefficient of Variation 37.3 |
| MK-4166 30 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 4 | 4.78 Liters | Geometric Coefficient of Variation 54.9 |
| MK-4166 30 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 2 | 5.29 Liters | Geometric Coefficient of Variation 9.3 |
| MK-4166 42 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 4 | 7.05 Liters | — |
| MK-4166 42 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 3 | 6.73 Liters | Geometric Coefficient of Variation 53.6 |
| MK-4166 42 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 1 | 5.84 Liters | Geometric Coefficient of Variation 28.1 |
| MK-4166 42 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 2 | 6.82 Liters | Geometric Coefficient of Variation 32.9 |
| MK-4166 59 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 1 | 4.10 Liters | Geometric Coefficient of Variation 6.1 |
| MK-4166 59 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 2 | 4.92 Liters | Geometric Coefficient of Variation 11.1 |
| MK-4166 59 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 4 | 4.47 Liters | — |
| MK-4166 59 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 3 | 4.40 Liters | Geometric Coefficient of Variation 7.7 |
| MK-4166 82 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 3 | 3.62 Liters | Geometric Coefficient of Variation 55 |
| MK-4166 82 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 1 | 4.25 Liters | Geometric Coefficient of Variation 37.9 |
| MK-4166 82 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 2 | 5.70 Liters | Geometric Coefficient of Variation 44.1 |
| MK-4166 120 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 3 | 6.51 Liters | Geometric Coefficient of Variation 62.6 |
| MK-4166 120 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 1 | 6.50 Liters | Geometric Coefficient of Variation 19.5 |
| MK-4166 120 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 2 | 7.34 Liters | Geometric Coefficient of Variation 92.9 |
| MK-4166 120 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 4 | 6.85 Liters | Geometric Coefficient of Variation 6.4 |
| MK-4166 170 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 1 | 4.62 Liters | Geometric Coefficient of Variation 23.8 |
| MK-4166 170 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 2 | 4.88 Liters | Geometric Coefficient of Variation 41.7 |
| MK-4166 170 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 3 | 3.63 Liters | Geometric Coefficient of Variation 20.5 |
| MK-4166 240 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 2 | 4.96 Liters | Geometric Coefficient of Variation 20 |
| MK-4166 240 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 3 | 3.24 Liters | — |
| MK-4166 240 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 1 | 4.27 Liters | Geometric Coefficient of Variation 4.5 |
| MK-4166 240 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 4 | 4.31 Liters | — |
| MK-4166 340 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 2 | 4.71 Liters | Geometric Coefficient of Variation 23.3 |
| MK-4166 340 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 1 | 4.43 Liters | Geometric Coefficient of Variation 4.2 |
| MK-4166 340 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 4 | 3.17 Liters | — |
| MK-4166 340 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 3 | 4.01 Liters | Geometric Coefficient of Variation 15.4 |
| MK-4166 480 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 1 | 3.61 Liters | Geometric Coefficient of Variation 30 |
| MK-4166 480 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 2 | 5.36 Liters | Geometric Coefficient of Variation 16.6 |
| MK-4166 480 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 3 | 2.64 Liters | Geometric Coefficient of Variation 33.9 |
| MK-4166 670 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 4 | 2.46 Liters | Geometric Coefficient of Variation 7.2 |
| MK-4166 670 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 3 | 5.66 Liters | Geometric Coefficient of Variation 14.9 |
| MK-4166 670 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 2 | 5.24 Liters | Geometric Coefficient of Variation 22.5 |
| MK-4166 670 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 1 | 3.78 Liters | Geometric Coefficient of Variation 16.7 |
| MK-4166 900 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 1 | 4.84 Liters | Geometric Coefficient of Variation 32.3 |
| MK-4166 900 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 3 | 7.09 Liters | Geometric Coefficient of Variation 73.6 |
| MK-4166 900 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 4 | 5.48 Liters | Geometric Coefficient of Variation 44.7 |
| MK-4166 900 mg + Pembro | Apparent Volume of Distribution (V) of Pembrolizumab Over Time | Cycle 2 | 5.79 Liters | Geometric Coefficient of Variation 38.6 |
Secondary
Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time
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.
Time frame: 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)
Population: All allocated participants who received at least 1 dose of MK-4166 and had evaluable AUC0-21 samples. Per protocol, %GCV values were not reported for cohorts with n\<2 participants. Participants with samples that were hemolyzed or analyzed outside of stability were excluded from the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-4166 0.0015 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 0.141 Days•ng/mL | — |
| MK-4166 0.0015 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 1.08 Days•ng/mL | — |
| MK-4166 0.0015 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 0.893 Days•ng/mL | — |
| MK-4166 0.0045 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 3.91 Days•ng/mL | — |
| MK-4166 0.014 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 24.7 Days•ng/mL | — |
| MK-4166 0.04 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 39.0 Days•ng/mL | — |
| MK-4166 0.04 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 126 Days•ng/mL | — |
| MK-4166 0.12 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 69.4 Days•ng/mL | — |
| MK-4166 0.12 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 118 Days•ng/mL | — |
| MK-4166 0.12 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 135 Days•ng/mL | — |
| MK-4166 0.37 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 2610 Days•ng/mL | — |
| MK-4166 0.37 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 672 Days•ng/mL | — |
| MK-4166 1.1 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 3140 Days•ng/mL | — |
| MK-4166 3.3 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 3510 Days•ng/mL | — |
| MK-4166 3.3 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 8300 Days•ng/mL | — |
| MK-4166 10 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 19100 Days•ng/mL | — |
| MK-4166 10 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | NA Days•ng/mL | — |
| MK-4166 10 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | NA Days•ng/mL | — |
| MK-4166 30 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 84700 Days•ng/mL | Geometric Coefficient of Variation 36.5 |
| MK-4166 30 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 48600 Days•ng/mL | Geometric Coefficient of Variation 226.2 |
| MK-4166 30 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 17400 Days•ng/mL | Geometric Coefficient of Variation 711.2 |
| MK-4166 42 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 55700 Days•ng/mL | Geometric Coefficient of Variation 733.9 |
| MK-4166 42 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 51800 Days•ng/mL | Geometric Coefficient of Variation 660.7 |
| MK-4166 42 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 18500 Days•ng/mL | Geometric Coefficient of Variation 8160 |
| MK-4166 42 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 111000 Days•ng/mL | Geometric Coefficient of Variation 32.9 |
| MK-4166 59 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 250000 Days•ng/mL | — |
| MK-4166 59 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 235000 Days•ng/mL | — |
| MK-4166 59 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 142000 Days•ng/mL | Geometric Coefficient of Variation 31.1 |
| MK-4166 59 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 14500 Days•ng/mL | Geometric Coefficient of Variation 19927 |
| MK-4166 82 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 217000 Days•ng/mL | Geometric Coefficient of Variation 87 |
| MK-4166 82 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 80600 Days•ng/mL | Geometric Coefficient of Variation 247.9 |
| MK-4166 82 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 226000 Days•ng/mL | Geometric Coefficient of Variation 46.3 |
| MK-4166 82 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 273000 Days•ng/mL | Geometric Coefficient of Variation 50.1 |
| MK-4166 120 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 223000 Days•ng/mL | Geometric Coefficient of Variation 45.6 |
| MK-4166 120 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | NA Days•ng/mL | — |
| MK-4166 120 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 291000 Days•ng/mL | Geometric Coefficient of Variation 39.6 |
| MK-4166 120 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 306000 Days•ng/mL | Geometric Coefficient of Variation 32.2 |
| MK-4166 170 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 503000 Days•ng/mL | Geometric Coefficient of Variation 133.9 |
| MK-4166 170 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 457000 Days•ng/mL | Geometric Coefficient of Variation 23.3 |
| MK-4166 170 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 401000 Days•ng/mL | Geometric Coefficient of Variation 55.9 |
| MK-4166 170 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 173000 Days•ng/mL | Geometric Coefficient of Variation 658.5 |
| MK-4166 240 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 426000 Days•ng/mL | Geometric Coefficient of Variation 30.4 |
| MK-4166 240 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 860000 Days•ng/mL | Geometric Coefficient of Variation 53.4 |
| MK-4166 240 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 749000 Days•ng/mL | Geometric Coefficient of Variation 6.8 |
| MK-4166 240 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 716000 Days•ng/mL | Geometric Coefficient of Variation 0.359 |
| MK-4166 340 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 770000 Days•ng/mL | Geometric Coefficient of Variation 59 |
| MK-4166 340 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 1160000 Days•ng/mL | Geometric Coefficient of Variation 72.1 |
| MK-4166 340 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 1180000 Days•ng/mL | Geometric Coefficient of Variation 69.4 |
| MK-4166 340 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 1410000 Days•ng/mL | — |
| MK-4166 480 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 1110000 Days•ng/mL | Geometric Coefficient of Variation 21.4 |
| MK-4166 480 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 1370000 Days•ng/mL | — |
| MK-4166 480 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 1590000 Days•ng/mL | Geometric Coefficient of Variation 33.3 |
| MK-4166 670 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 2390000 Days•ng/mL | — |
| MK-4166 670 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 1400000 Days•ng/mL | — |
| MK-4166 670 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 2090000 Days•ng/mL | Geometric Coefficient of Variation 19.8 |
| MK-4166 670 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 1730000 Days•ng/mL | Geometric Coefficient of Variation 28.7 |
| MK-4166 900 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 3110000 Days•ng/mL | Geometric Coefficient of Variation 17.5 |
| MK-4166 900 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | NA Days•ng/mL | — |
| MK-4166 900 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 5410000 Days•ng/mL | Geometric Coefficient of Variation 4.01 |
| MK-4166 900 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 4580000 Days•ng/mL | Geometric Coefficient of Variation 21.1 |
| MK-4166 1.1 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 7700 Days•ng/mL | Geometric Coefficient of Variation 32.6 |
| MK-4166 1.1 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 1120 Days•ng/mL | Geometric Coefficient of Variation 120.6 |
| MK-4166 1.1 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | NA Days•ng/mL | — |
| MK-4166 1.1 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 1110 Days•ng/mL | Geometric Coefficient of Variation 104.1 |
| MK-4166 3.3 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 7330 Days•ng/mL | Geometric Coefficient of Variation 150.8 |
| MK-4166 3.3 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 19900 Days•ng/mL | Geometric Coefficient of Variation 87.1 |
| MK-4166 3.3 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 33900 Days•ng/mL | Geometric Coefficient of Variation 8.86 |
| MK-4166 10 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 79300 Days•ng/mL | — |
| MK-4166 10 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 6380 Days•ng/mL | Geometric Coefficient of Variation 503154.6 |
| MK-4166 10 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 80400 Days•ng/mL | — |
| MK-4166 10 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 33800 Days•ng/mL | Geometric Coefficient of Variation 89.1 |
| MK-4166 30 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 107000 Days•ng/mL | Geometric Coefficient of Variation 136.8 |
| MK-4166 30 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 167000 Days•ng/mL | Geometric Coefficient of Variation 56.9 |
| MK-4166 30 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 182000 Days•ng/mL | Geometric Coefficient of Variation 81.4 |
| MK-4166 30 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 137000 Days•ng/mL | Geometric Coefficient of Variation 41.4 |
| MK-4166 42 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 116000 Days•ng/mL | Geometric Coefficient of Variation 121.4 |
| MK-4166 42 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 353000 Days•ng/mL | — |
| MK-4166 42 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 119000 Days•ng/mL | Geometric Coefficient of Variation 71.4 |
| MK-4166 42 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 123000 Days•ng/mL | Geometric Coefficient of Variation 156.1 |
| MK-4166 59 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 152000 Days•ng/mL | Geometric Coefficient of Variation 11.5 |
| MK-4166 59 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 216000 Days•ng/mL | Geometric Coefficient of Variation 32.4 |
| MK-4166 59 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 148000 Days•ng/mL | Geometric Coefficient of Variation 24.9 |
| MK-4166 59 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 147000 Days•ng/mL | Geometric Coefficient of Variation 25.9 |
| MK-4166 82 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 301000 Days•ng/mL | Geometric Coefficient of Variation 27.7 |
| MK-4166 82 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 271000 Days•ng/mL | Geometric Coefficient of Variation 25 |
| MK-4166 82 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 278000 Days•ng/mL | Geometric Coefficient of Variation 37.1 |
| MK-4166 120 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 279000 Days•ng/mL | Geometric Coefficient of Variation 84.3 |
| MK-4166 120 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 394000 Days•ng/mL | Geometric Coefficient of Variation 66 |
| MK-4166 120 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 248000 Days•ng/mL | Geometric Coefficient of Variation 57.6 |
| MK-4166 120 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 330000 Days•ng/mL | Geometric Coefficient of Variation 79.3 |
| MK-4166 170 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 516000 Days•ng/mL | Geometric Coefficient of Variation 21.1 |
| MK-4166 170 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 594000 Days•ng/mL | Geometric Coefficient of Variation 27.1 |
| MK-4166 170 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 631000 Days•ng/mL | Geometric Coefficient of Variation 10.4 |
| MK-4166 170 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 575000 Days•ng/mL | — |
| MK-4166 240 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 1170000 Days•ng/mL | Geometric Coefficient of Variation 15.1 |
| MK-4166 240 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 1580000 Days•ng/mL | Geometric Coefficient of Variation 46.2 |
| MK-4166 240 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 1310000 Days•ng/mL | Geometric Coefficient of Variation 18.8 |
| MK-4166 240 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 832000 Days•ng/mL | Geometric Coefficient of Variation 11.4 |
| MK-4166 340 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 692000 Days•ng/mL | Geometric Coefficient of Variation 277.7 |
| MK-4166 340 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 2350000 Days•ng/mL | — |
| MK-4166 340 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 986000 Days•ng/mL | Geometric Coefficient of Variation 26.2 |
| MK-4166 340 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 678000 Days•ng/mL | Geometric Coefficient of Variation 305.7 |
| MK-4166 480 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 137000 Days•ng/mL | Geometric Coefficient of Variation 7.7 |
| MK-4166 480 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 1760000 Days•ng/mL | Geometric Coefficient of Variation 11.9 |
| MK-4166 480 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 2220000 Days•ng/mL | — |
| MK-4166 670 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 3440000 Days•ng/mL | Geometric Coefficient of Variation 7.9 |
| MK-4166 670 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 3280000 Days•ng/mL | Geometric Coefficient of Variation 5.08 |
| MK-4166 670 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 1740000 Days•ng/mL | Geometric Coefficient of Variation 50.3 |
| MK-4166 670 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 3800000 Days•ng/mL | — |
| MK-4166 900 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 2880000 Days•ng/mL | Geometric Coefficient of Variation 49 |
| MK-4166 900 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 3790000 Days•ng/mL | Geometric Coefficient of Variation 28.7 |
| MK-4166 900 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 2130000 Days•ng/mL | Geometric Coefficient of Variation 27.5 |
| MK-4166 900 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 4360000 Days•ng/mL | Geometric Coefficient of Variation 33.7 |
Secondary
Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time
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.
Time frame: 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)
Population: All allocated participants who received at least 1 dose of MK-4166 and had evaluable AUC0-inf samples. Per protocol, %GCV values were not reported for cohorts with n\<2 participants. Participants with samples that were hemolyzed or analyzed outside of stability were excluded from the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-4166 0.0015 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 1.09 Days•ng/mL | — |
| MK-4166 0.0015 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | NA Days•ng/mL | — |
| MK-4166 0.0015 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 0.896 Days•ng/mL | — |
| MK-4166 0.0045 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 3.92 Days•ng/mL | — |
| MK-4166 0.014 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 24.8 Days•ng/mL | — |
| MK-4166 0.04 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 126 Days•ng/mL | — |
| MK-4166 0.04 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 39.3 Days•ng/mL | — |
| MK-4166 0.12 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 118 Days•ng/mL | — |
| MK-4166 0.12 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 69.5 Days•ng/mL | — |
| MK-4166 0.12 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 135 Days•ng/mL | — |
| MK-4166 0.37 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 673 Days•ng/mL | — |
| MK-4166 0.37 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 2660 Days•ng/mL | — |
| MK-4166 1.1 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 3190 Days•ng/mL | — |
| MK-4166 3.3 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 8420 Days•ng/mL | — |
| MK-4166 3.3 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 3490 Days•ng/mL | — |
| MK-4166 10 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | NA Days•ng/mL | — |
| MK-4166 10 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 29400 Days•ng/mL | — |
| MK-4166 10 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | NA Days•ng/mL | — |
| MK-4166 30 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 18700 Days•ng/mL | Geometric Coefficient of Variation 896 |
| MK-4166 30 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 105000 Days•ng/mL | Geometric Coefficient of Variation 54 |
| MK-4166 30 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 58600 Days•ng/mL | Geometric Coefficient of Variation 326.9 |
| MK-4166 42 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 18200 Days•ng/mL | Geometric Coefficient of Variation 20134.8 |
| MK-4166 42 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 68800 Days•ng/mL | Geometric Coefficient of Variation 1111.6 |
| MK-4166 42 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 70000 Days•ng/mL | Geometric Coefficient of Variation 1119.8 |
| MK-4166 42 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 141000 Days•ng/mL | Geometric Coefficient of Variation 55.5 |
| MK-4166 59 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 15400 Days•ng/mL | Geometric Coefficient of Variation 28630.7 |
| MK-4166 59 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 309000 Days•ng/mL | — |
| MK-4166 59 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 330000 Days•ng/mL | — |
| MK-4166 59 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 148000 Days•ng/mL | Geometric Coefficient of Variation 37.7 |
| MK-4166 82 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 333000 Days•ng/mL | Geometric Coefficient of Variation 59.5 |
| MK-4166 82 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 360000 Days•ng/mL | Geometric Coefficient of Variation 68.6 |
| MK-4166 82 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 251000 Days•ng/mL | Geometric Coefficient of Variation 105.1 |
| MK-4166 82 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 85500 Days•ng/mL | Geometric Coefficient of Variation 284.2 |
| MK-4166 120 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | NA Days•ng/mL | — |
| MK-4166 120 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 396000 Days•ng/mL | Geometric Coefficient of Variation 53.5 |
| MK-4166 120 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 345000 Days•ng/mL | Geometric Coefficient of Variation 54.4 |
| MK-4166 120 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 252000 Days•ng/mL | Geometric Coefficient of Variation 59.2 |
| MK-4166 170 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 644000 Days•ng/mL | Geometric Coefficient of Variation 228.9 |
| MK-4166 170 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 216000 Days•ng/mL | Geometric Coefficient of Variation 1232.6 |
| MK-4166 170 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 558000 Days•ng/mL | Geometric Coefficient of Variation 31.1 |
| MK-4166 170 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 503000 Days•ng/mL | Geometric Coefficient of Variation 78.7 |
| MK-4166 240 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 501000 Days•ng/mL | Geometric Coefficient of Variation 51.5 |
| MK-4166 240 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 1050000 Days•ng/mL | Geometric Coefficient of Variation 2.7 |
| MK-4166 240 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 862000 Days•ng/mL | Geometric Coefficient of Variation 4.6 |
| MK-4166 240 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 1280000 Days•ng/mL | Geometric Coefficient of Variation 6.1 |
| MK-4166 340 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 1120000 Days•ng/mL | Geometric Coefficient of Variation 67.1 |
| MK-4166 340 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 2520000 Days•ng/mL | — |
| MK-4166 340 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 1690000 Days•ng/mL | Geometric Coefficient of Variation 69.9 |
| MK-4166 340 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 1740000 Days•ng/mL | Geometric Coefficient of Variation 71.9 |
| MK-4166 480 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 2090000 Days•ng/mL | Geometric Coefficient of Variation 39.2 |
| MK-4166 480 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 1880000 Days•ng/mL | — |
| MK-4166 480 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 1500000 Days•ng/mL | Geometric Coefficient of Variation 17.2 |
| MK-4166 670 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 1460000 Days•ng/mL | — |
| MK-4166 670 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 3190000 Days•ng/mL | — |
| MK-4166 670 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 2580000 Days•ng/mL | Geometric Coefficient of Variation 9.88 |
| MK-4166 670 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 2950000 Days•ng/mL | Geometric Coefficient of Variation 4.1 |
| MK-4166 900 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 4520000 Days•ng/mL | Geometric Coefficient of Variation 19.2 |
| MK-4166 900 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 11300000 Days•ng/mL | Geometric Coefficient of Variation 33.8 |
| MK-4166 900 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 7270000 Days•ng/mL | Geometric Coefficient of Variation 0.2 |
| MK-4166 900 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | NA Days•ng/mL | — |
| MK-4166 1.1 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 7750 Days•ng/mL | Geometric Coefficient of Variation 32.8 |
| MK-4166 1.1 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | NA Days•ng/mL | — |
| MK-4166 1.1 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 1550 Days•ng/mL | Geometric Coefficient of Variation 49.7 |
| MK-4166 1.1 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 1210 Days•ng/mL | Geometric Coefficient of Variation 104.1 |
| MK-4166 3.3 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 35700 Days•ng/mL | Geometric Coefficient of Variation 1.4 |
| MK-4166 3.3 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 20600 Days•ng/mL | Geometric Coefficient of Variation 89.4 |
| MK-4166 3.3 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 7010 Days•ng/mL | Geometric Coefficient of Variation 176.2 |
| MK-4166 10 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 7660 Days•ng/mL | Geometric Coefficient of Variation 2164569 |
| MK-4166 10 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 136000 Days•ng/mL | — |
| MK-4166 10 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 40200 Days•ng/mL | Geometric Coefficient of Variation 121.9 |
| MK-4166 10 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 92300 Days•ng/mL | — |
| MK-4166 30 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 129000 Days•ng/mL | Geometric Coefficient of Variation 200.9 |
| MK-4166 30 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 232000 Days•ng/mL | Geometric Coefficient of Variation 92 |
| MK-4166 30 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 200000 Days•ng/mL | Geometric Coefficient of Variation 74.6 |
| MK-4166 30 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 261000 Days•ng/mL | Geometric Coefficient of Variation 123.7 |
| MK-4166 42 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 155000 Days•ng/mL | Geometric Coefficient of Variation 236.1 |
| MK-4166 42 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 524000 Days•ng/mL | — |
| MK-4166 42 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 141000 Days•ng/mL | Geometric Coefficient of Variation 168.9 |
| MK-4166 42 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 142000 Days•ng/mL | Geometric Coefficient of Variation 90.1 |
| MK-4166 59 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 162000 Days•ng/mL | Geometric Coefficient of Variation 15.6 |
| MK-4166 59 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 187000 Days•ng/mL | Geometric Coefficient of Variation 46 |
| MK-4166 59 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 164000 Days•ng/mL | Geometric Coefficient of Variation 22.9 |
| MK-4166 59 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 238000 Days•ng/mL | Geometric Coefficient of Variation 40.4 |
| MK-4166 82 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 392000 Days•ng/mL | Geometric Coefficient of Variation 38.9 |
| MK-4166 82 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 336000 Days•ng/mL | Geometric Coefficient of Variation 23.4 |
| MK-4166 82 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 360000 Days•ng/mL | Geometric Coefficient of Variation 28.9 |
| MK-4166 120 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 609000 Days•ng/mL | Geometric Coefficient of Variation 96.4 |
| MK-4166 120 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 430000 Days•ng/mL | Geometric Coefficient of Variation 86.6 |
| MK-4166 120 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 385000 Days•ng/mL | Geometric Coefficient of Variation 150 |
| MK-4166 120 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 338000 Days•ng/mL | Geometric Coefficient of Variation 76.2 |
| MK-4166 170 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 730000 Days•ng/mL | Geometric Coefficient of Variation 15.9 |
| MK-4166 170 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 849000 Days•ng/mL | Geometric Coefficient of Variation 15.3 |
| MK-4166 170 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 915000 Days•ng/mL | Geometric Coefficient of Variation 17.1 |
| MK-4166 170 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 914000 Days•ng/mL | — |
| MK-4166 240 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 2740000 Days•ng/mL | Geometric Coefficient of Variation 52.3 |
| MK-4166 240 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 1930000 Days•ng/mL | Geometric Coefficient of Variation 20.7 |
| MK-4166 240 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 2720000 Days•ng/mL | Geometric Coefficient of Variation 67.4 |
| MK-4166 240 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 1240000 Days•ng/mL | Geometric Coefficient of Variation 12.4 |
| MK-4166 340 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 3480000 Days•ng/mL | — |
| MK-4166 340 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 1300000 Days•ng/mL | Geometric Coefficient of Variation 52.3 |
| MK-4166 340 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 909000 Days•ng/mL | Geometric Coefficient of Variation 438.2 |
| MK-4166 340 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 874000 Days•ng/mL | Geometric Coefficient of Variation 450.1 |
| MK-4166 480 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 2500000 Days•ng/mL | Geometric Coefficient of Variation 18.6 |
| MK-4166 480 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 2090000 Days•ng/mL | Geometric Coefficient of Variation 26.2 |
| MK-4166 480 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 3910000 Days•ng/mL | — |
| MK-4166 670 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 5690000 Days•ng/mL | Geometric Coefficient of Variation 2.23 |
| MK-4166 670 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 5400000 Days•ng/mL | — |
| MK-4166 670 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 5570000 Days•ng/mL | Geometric Coefficient of Variation 8.3 |
| MK-4166 670 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 2340000 Days•ng/mL | Geometric Coefficient of Variation 77 |
| MK-4166 900 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 3200000 Days•ng/mL | Geometric Coefficient of Variation 43 |
| MK-4166 900 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 4520000 Days•ng/mL | Geometric Coefficient of Variation 70.6 |
| MK-4166 900 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 7910000 Days•ng/mL | Geometric Coefficient of Variation 54.9 |
| MK-4166 900 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 8000000 Days•ng/mL | Geometric Coefficient of Variation 82.8 |
Secondary
Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time
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.
Time frame: 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)
Population: All allocated participants who received at least 1 dose of MK-4166 and had evaluable AUC0-last samples. Per protocol, %GCV values were not reported for cohorts with n\<2 participants. Participants with samples that were hemolyzed or analyzed outside of stability were excluded from the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-4166 0.0015 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 0.879 Days•ng/mL | — |
| MK-4166 0.0015 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 0.0632 Days•ng/mL | — |
| MK-4166 0.0015 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 1.08 Days•ng/mL | — |
| MK-4166 0.0045 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 3.89 Days•ng/mL | — |
| MK-4166 0.014 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 24.6 Days•ng/mL | — |
| MK-4166 0.04 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 86.9 Days•ng/mL | — |
| MK-4166 0.04 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 39.0 Days•ng/mL | — |
| MK-4166 0.12 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 69.4 Days•ng/mL | — |
| MK-4166 0.12 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 118 Days•ng/mL | — |
| MK-4166 0.12 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 135 Days•ng/mL | — |
| MK-4166 0.37 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 672 Days•ng/mL | — |
| MK-4166 0.37 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 2010 Days•ng/mL | — |
| MK-4166 1.1 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 3010 Days•ng/mL | — |
| MK-4166 3.3 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 1780 Days•ng/mL | — |
| MK-4166 3.3 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 8300 Days•ng/mL | — |
| MK-4166 10 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 21.1 Days•ng/mL | — |
| MK-4166 10 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 7.48 Days•ng/mL | — |
| MK-4166 10 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 14300 Days•ng/mL | — |
| MK-4166 30 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 79500 Days•ng/mL | Geometric Coefficient of Variation 34.6 |
| MK-4166 30 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 19600 Days•ng/mL | Geometric Coefficient of Variation 351.9 |
| MK-4166 30 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 48600 Days•ng/mL | Geometric Coefficient of Variation 226.2 |
| MK-4166 42 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 51400 Days•ng/mL | Geometric Coefficient of Variation 640.7 |
| MK-4166 42 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 111000 Days•ng/mL | Geometric Coefficient of Variation 32.7 |
| MK-4166 42 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 51600 Days•ng/mL | Geometric Coefficient of Variation 660.6 |
| MK-4166 42 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 11500 Days•ng/mL | Geometric Coefficient of Variation 4140.6 |
| MK-4166 59 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 14600 Days•ng/mL | Geometric Coefficient of Variation 18895.8 |
| MK-4166 59 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 14400 Days•ng/mL | Geometric Coefficient of Variation 20883.7 |
| MK-4166 59 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 141000 Days•ng/mL | Geometric Coefficient of Variation 31.6 |
| MK-4166 59 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 25300 Days•ng/mL | Geometric Coefficient of Variation 14504.2 |
| MK-4166 82 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 226000 Days•ng/mL | Geometric Coefficient of Variation 46.4 |
| MK-4166 82 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 268000 Days•ng/mL | Geometric Coefficient of Variation 49.1 |
| MK-4166 82 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 172000 Days•ng/mL | Geometric Coefficient of Variation 69.1 |
| MK-4166 82 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 61500 Days•ng/mL | Geometric Coefficient of Variation 136.5 |
| MK-4166 120 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 79100 Days•ng/mL | Geometric Coefficient of Variation 265 |
| MK-4166 120 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 281000 Days•ng/mL | Geometric Coefficient of Variation 19.5 |
| MK-4166 120 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 290000 Days•ng/mL | Geometric Coefficient of Variation 39.4 |
| MK-4166 120 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 223000 Days•ng/mL | Geometric Coefficient of Variation 45.3 |
| MK-4166 170 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 168000 Days•ng/mL | Geometric Coefficient of Variation 728.3 |
| MK-4166 170 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 184000 Days•ng/mL | Geometric Coefficient of Variation 174.6 |
| MK-4166 170 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 451000 Days•ng/mL | Geometric Coefficient of Variation 23.9 |
| MK-4166 170 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 128000 Days•ng/mL | Geometric Coefficient of Variation 759 |
| MK-4166 240 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 864000 Days•ng/mL | Geometric Coefficient of Variation 54.7 |
| MK-4166 240 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 354000 Days•ng/mL | Geometric Coefficient of Variation 51.6 |
| MK-4166 240 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 756000 Days•ng/mL | Geometric Coefficient of Variation 5 |
| MK-4166 240 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 379000 Days•ng/mL | Geometric Coefficient of Variation 5.5 |
| MK-4166 340 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 677000 Days•ng/mL | Geometric Coefficient of Variation 82.2 |
| MK-4166 340 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 1160000 Days•ng/mL | Geometric Coefficient of Variation 72.3 |
| MK-4166 340 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 1110000 Days•ng/mL | Geometric Coefficient of Variation 59.1 |
| MK-4166 340 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 254000 Days•ng/mL | Geometric Coefficient of Variation 175 |
| MK-4166 480 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 1110000 Days•ng/mL | — |
| MK-4166 480 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 635000 Days•ng/mL | Geometric Coefficient of Variation 247.7 |
| MK-4166 480 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 1170000 Days•ng/mL | Geometric Coefficient of Variation 31.1 |
| MK-4166 670 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 2400000 Days•ng/mL | — |
| MK-4166 670 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 433000 Days•ng/mL | — |
| MK-4166 670 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 1720000 Days•ng/mL | Geometric Coefficient of Variation 29 |
| MK-4166 670 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 1790000 Days•ng/mL | Geometric Coefficient of Variation 31.7 |
| MK-4166 900 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 469000 Days•ng/mL | — |
| MK-4166 900 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 2620000 Days•ng/mL | Geometric Coefficient of Variation 116.6 |
| MK-4166 900 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 3310000 Days•ng/mL | Geometric Coefficient of Variation 17.1 |
| MK-4166 900 mg | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 1910000 Days•ng/mL | Geometric Coefficient of Variation 294 |
| MK-4166 1.1 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 740 Days•ng/mL | Geometric Coefficient of Variation 53.9 |
| MK-4166 1.1 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 1110 Days•ng/mL | Geometric Coefficient of Variation 118.9 |
| MK-4166 1.1 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 7700 Days•ng/mL | Geometric Coefficient of Variation 32.6 |
| MK-4166 1.1 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 1.72 Days•ng/mL | — |
| MK-4166 3.3 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 14100 Days•ng/mL | Geometric Coefficient of Variation 57.6 |
| MK-4166 3.3 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 4070 Days•ng/mL | Geometric Coefficient of Variation 18558.6 |
| MK-4166 3.3 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 6510 Days•ng/mL | Geometric Coefficient of Variation 182.3 |
| MK-4166 10 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 5130 Days•ng/mL | Geometric Coefficient of Variation 177486.3 |
| MK-4166 10 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 46000 Days•ng/mL | — |
| MK-4166 10 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 31900 Days•ng/mL | Geometric Coefficient of Variation 88.8 |
| MK-4166 10 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 309 Days•ng/mL | Geometric Coefficient of Variation 4954684876.5 |
| MK-4166 30 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 137000 Days•ng/mL | Geometric Coefficient of Variation 41.5 |
| MK-4166 30 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 162000 Days•ng/mL | Geometric Coefficient of Variation 63.3 |
| MK-4166 30 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 167000 Days•ng/mL | Geometric Coefficient of Variation 56.9 |
| MK-4166 30 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 80800 Days•ng/mL | Geometric Coefficient of Variation 140.8 |
| MK-4166 42 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 12600 Days•ng/mL | Geometric Coefficient of Variation 1377431.1 |
| MK-4166 42 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 120000 Days•ng/mL | Geometric Coefficient of Variation 71 |
| MK-4166 42 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 118000 Days•ng/mL | Geometric Coefficient of Variation 153.4 |
| MK-4166 42 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 115000 Days•ng/mL | Geometric Coefficient of Variation 121.4 |
| MK-4166 59 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 142000 Days•ng/mL | Geometric Coefficient of Variation 31.9 |
| MK-4166 59 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 142000 Days•ng/mL | Geometric Coefficient of Variation 39.4 |
| MK-4166 59 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 228000 Days•ng/mL | Geometric Coefficient of Variation 40.9 |
| MK-4166 59 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 153000 Days•ng/mL | Geometric Coefficient of Variation 12.2 |
| MK-4166 82 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 219000 Days•ng/mL | Geometric Coefficient of Variation 18.5 |
| MK-4166 82 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 200000 Days•ng/mL | Geometric Coefficient of Variation 76.6 |
| MK-4166 82 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 280000 Days•ng/mL | Geometric Coefficient of Variation 35.7 |
| MK-4166 120 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 365000 Days•ng/mL | Geometric Coefficient of Variation 44.1 |
| MK-4166 120 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 323000 Days•ng/mL | Geometric Coefficient of Variation 80.9 |
| MK-4166 120 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 280000 Days•ng/mL | Geometric Coefficient of Variation 83.6 |
| MK-4166 120 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 248000 Days•ng/mL | Geometric Coefficient of Variation 57.5 |
| MK-4166 170 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 579000 Days•ng/mL | Geometric Coefficient of Variation 14.8 |
| MK-4166 170 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 616000 Days•ng/mL | Geometric Coefficient of Variation 25.9 |
| MK-4166 170 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 477000 Days•ng/mL | Geometric Coefficient of Variation 16.2 |
| MK-4166 170 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 574000 Days•ng/mL | — |
| MK-4166 240 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 830000 Days•ng/mL | Geometric Coefficient of Variation 11.3 |
| MK-4166 240 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 638000 Days•ng/mL | Geometric Coefficient of Variation 195.6 |
| MK-4166 240 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 1170000 Days•ng/mL | Geometric Coefficient of Variation 13.7 |
| MK-4166 240 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 1580000 Days•ng/mL | Geometric Coefficient of Variation 46.6 |
| MK-4166 340 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 967000 Days•ng/mL | Geometric Coefficient of Variation 25.3 |
| MK-4166 340 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 2280000 Days•ng/mL | — |
| MK-4166 340 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 681000 Days•ng/mL | Geometric Coefficient of Variation 307 |
| MK-4166 340 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 443000 Days•ng/mL | Geometric Coefficient of Variation 353.2 |
| MK-4166 480 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 738000 Days•ng/mL | Geometric Coefficient of Variation 141.5 |
| MK-4166 480 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 473000 Days•ng/mL | Geometric Coefficient of Variation 480 |
| MK-4166 480 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 1710000 Days•ng/mL | Geometric Coefficient of Variation 15.7 |
| MK-4166 670 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 975000 Days•ng/mL | Geometric Coefficient of Variation 99.2 |
| MK-4166 670 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 3770000 Days•ng/mL | Geometric Coefficient of Variation 25.4 |
| MK-4166 670 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 1280000 Days•ng/mL | Geometric Coefficient of Variation 126.2 |
| MK-4166 670 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 3480000 Days•ng/mL | Geometric Coefficient of Variation 6.2 |
| MK-4166 900 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 3920000 Days•ng/mL | Geometric Coefficient of Variation 29.1 |
| MK-4166 900 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 1710000 Days•ng/mL | Geometric Coefficient of Variation 371.9 |
| MK-4166 900 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 2750000 Days•ng/mL | Geometric Coefficient of Variation 135.4 |
| MK-4166 900 mg + Pembro | Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 2140000 Days•ng/mL | Geometric Coefficient of Variation 27.5 |
Secondary
Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time
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.
Time frame: 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)
Population: All allocated participants who received ≥1 dose of pembrolizumab and had evaluable AUC0-21 samples. Per protocol, %GCV values were not reported for cohorts with n\<2 participants, and MK-4166 monotherapy dose cohorts were not analyzed. Participants with samples that were hemolyzed or analyzed outside of stability were excluded from the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-4166 1.1 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 587000 Days•ng/mL | Geometric Coefficient of Variation 36 |
| MK-4166 1.1 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 913000 Days•ng/mL | Geometric Coefficient of Variation 53.8 |
| MK-4166 1.1 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 1540000 Days•ng/mL | — |
| MK-4166 1.1 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 847000 Days•ng/mL | Geometric Coefficient of Variation 33.5 |
| MK-4166 3.3 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 484000 Days•ng/mL | Geometric Coefficient of Variation 33.8 |
| MK-4166 3.3 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 662000 Days•ng/mL | Geometric Coefficient of Variation 38.5 |
| MK-4166 3.3 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 490000 Days•ng/mL | — |
| MK-4166 3.3 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 672000 Days•ng/mL | Geometric Coefficient of Variation 45.4 |
| MK-4166 10 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 405000 Days•ng/mL | Geometric Coefficient of Variation 62.8 |
| MK-4166 10 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 622000 Days•ng/mL | Geometric Coefficient of Variation 2.3 |
| MK-4166 10 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 408000 Days•ng/mL | Geometric Coefficient of Variation 10.7 |
| MK-4166 10 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 613000 Days•ng/mL | — |
| MK-4166 30 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 1050000 Days•ng/mL | Geometric Coefficient of Variation 38.7 |
| MK-4166 30 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 664000 Days•ng/mL | Geometric Coefficient of Variation 15.8 |
| MK-4166 30 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 952000 Days•ng/mL | Geometric Coefficient of Variation 12.6 |
| MK-4166 30 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 1120000 Days•ng/mL | Geometric Coefficient of Variation 14.1 |
| MK-4166 42 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 1370000 Days•ng/mL | — |
| MK-4166 42 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 633000 Days•ng/mL | Geometric Coefficient of Variation 59.6 |
| MK-4166 42 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 404000 Days•ng/mL | Geometric Coefficient of Variation 46.4 |
| MK-4166 42 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 579000 Days•ng/mL | Geometric Coefficient of Variation 46.1 |
| MK-4166 59 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 1010000 Days•ng/mL | Geometric Coefficient of Variation 14.7 |
| MK-4166 59 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 927000 Days•ng/mL | Geometric Coefficient of Variation 8.1 |
| MK-4166 59 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 871000 Days•ng/mL | Geometric Coefficient of Variation 16.5 |
| MK-4166 59 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 511000 Days•ng/mL | Geometric Coefficient of Variation 32.3 |
| MK-4166 82 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 738000 Days•ng/mL | Geometric Coefficient of Variation 37.4 |
| MK-4166 82 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 535000 Days•ng/mL | Geometric Coefficient of Variation 31.1 |
| MK-4166 82 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 750000 Days•ng/mL | Geometric Coefficient of Variation 47.9 |
| MK-4166 120 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 454000 Days•ng/mL | Geometric Coefficient of Variation 26 |
| MK-4166 120 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 739000 Days•ng/mL | Geometric Coefficient of Variation 48.8 |
| MK-4166 120 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 964000 Days•ng/mL | Geometric Coefficient of Variation 41.8 |
| MK-4166 120 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 903000 Days•ng/mL | Geometric Coefficient of Variation 50.6 |
| MK-4166 170 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 516000 Days•ng/mL | Geometric Coefficient of Variation 29 |
| MK-4166 170 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 752000 Days•ng/mL | Geometric Coefficient of Variation 27.4 |
| MK-4166 170 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 715000 Days•ng/mL | Geometric Coefficient of Variation 27.9 |
| MK-4166 240 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 1220000 Days•ng/mL | — |
| MK-4166 240 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 664000 Days•ng/mL | Geometric Coefficient of Variation 9.7 |
| MK-4166 240 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 921000 Days•ng/mL | Geometric Coefficient of Variation 18.1 |
| MK-4166 240 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 1370000 Days•ng/mL | — |
| MK-4166 340 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 560000 Days•ng/mL | Geometric Coefficient of Variation 26.5 |
| MK-4166 340 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 822000 Days•ng/mL | Geometric Coefficient of Variation 30.2 |
| MK-4166 340 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 825000 Days•ng/mL | Geometric Coefficient of Variation 21 |
| MK-4166 340 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 1460000 Days•ng/mL | — |
| MK-4166 480 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 991000 Days•ng/mL | Geometric Coefficient of Variation 14.5 |
| MK-4166 480 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 485000 Days•ng/mL | Geometric Coefficient of Variation 92.9 |
| MK-4166 480 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 883000 Days•ng/mL | Geometric Coefficient of Variation 25.5 |
| MK-4166 670 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 599000 Days•ng/mL | Geometric Coefficient of Variation 34.6 |
| MK-4166 670 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 967000 Days•ng/mL | Geometric Coefficient of Variation 6.3 |
| MK-4166 670 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 925000 Days•ng/mL | Geometric Coefficient of Variation 7.5 |
| MK-4166 670 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 810000 Days•ng/mL | Geometric Coefficient of Variation 27.7 |
| MK-4166 900 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 1 | 619000 Days•ng/mL | Geometric Coefficient of Variation 33.9 |
| MK-4166 900 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 3 | 1010000 Days•ng/mL | Geometric Coefficient of Variation 25.2 |
| MK-4166 900 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 4 | 892000 Days•ng/mL | Geometric Coefficient of Variation 59.3 |
| MK-4166 900 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time | Cycle 2 | 825000 Days•ng/mL | Geometric Coefficient of Variation 32.1 |
Secondary
Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time
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.
Time frame: 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)
Population: All allocated participants who received ≥1 dose of pembrolizumab and had evaluable AUC0-inf samples. Per protocol, %GCV values were not reported for cohorts with n\<2 participants, and MK-4166 monotherapy dose cohorts were not analyzed. Participants with samples that were hemolyzed or analyzed outside of stability were excluded from the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-4166 1.1 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 985000 Days•ng/mL | Geometric Coefficient of Variation 28 |
| MK-4166 1.1 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 1440000 Days•ng/mL | Geometric Coefficient of Variation 94.2 |
| MK-4166 1.1 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 1450000 Days•ng/mL | Geometric Coefficient of Variation 51.4 |
| MK-4166 1.1 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 2670000 Days•ng/mL | — |
| MK-4166 3.3 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 890000 Days•ng/mL | Geometric Coefficient of Variation 44.1 |
| MK-4166 3.3 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 667000 Days•ng/mL | — |
| MK-4166 3.3 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 1280000 Days•ng/mL | Geometric Coefficient of Variation 47.7 |
| MK-4166 3.3 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 709000 Days•ng/mL | Geometric Coefficient of Variation 46.3 |
| MK-4166 10 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 816000 Days•ng/mL | — |
| MK-4166 10 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 1000000 Days•ng/mL | Geometric Coefficient of Variation 21.1 |
| MK-4166 10 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 647000 Days•ng/mL | Geometric Coefficient of Variation 11.8 |
| MK-4166 10 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 655000 Days•ng/mL | Geometric Coefficient of Variation 104.6 |
| MK-4166 30 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 1870000 Days•ng/mL | Geometric Coefficient of Variation 36.7 |
| MK-4166 30 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 1700000 Days•ng/mL | Geometric Coefficient of Variation 21.3 |
| MK-4166 30 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 1980000 Days•ng/mL | Geometric Coefficient of Variation 118.7 |
| MK-4166 30 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 1400000 Days•ng/mL | Geometric Coefficient of Variation 15.6 |
| MK-4166 42 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 3890000 Days•ng/mL | — |
| MK-4166 42 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 1110000 Days•ng/mL | Geometric Coefficient of Variation 149 |
| MK-4166 42 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 915000 Days•ng/mL | Geometric Coefficient of Variation 75.1 |
| MK-4166 42 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 582000 Days•ng/mL | Geometric Coefficient of Variation 65.7 |
| MK-4166 59 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 1450000 Days•ng/mL | Geometric Coefficient of Variation 7 |
| MK-4166 59 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 666000 Days•ng/mL | Geometric Coefficient of Variation 54.4 |
| MK-4166 59 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 1430000 Days•ng/mL | — |
| MK-4166 59 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 1410000 Days•ng/mL | Geometric Coefficient of Variation 19.6 |
| MK-4166 82 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 740000 Days•ng/mL | Geometric Coefficient of Variation 39 |
| MK-4166 82 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 1210000 Days•ng/mL | Geometric Coefficient of Variation 50.6 |
| MK-4166 82 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 949000 Days•ng/mL | Geometric Coefficient of Variation 37 |
| MK-4166 120 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 1770000 Days•ng/mL | Geometric Coefficient of Variation 41.9 |
| MK-4166 120 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 1390000 Days•ng/mL | Geometric Coefficient of Variation 24.5 |
| MK-4166 120 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 2070000 Days•ng/mL | Geometric Coefficient of Variation 71.7 |
| MK-4166 120 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 786000 Days•ng/mL | Geometric Coefficient of Variation 37.5 |
| MK-4166 170 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 703000 Days•ng/mL | Geometric Coefficient of Variation 36 |
| MK-4166 170 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 954000 Days•ng/mL | Geometric Coefficient of Variation 30.3 |
| MK-4166 170 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 1030000 Days•ng/mL | Geometric Coefficient of Variation 19.3 |
| MK-4166 240 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 1090000 Days•ng/mL | Geometric Coefficient of Variation 23 |
| MK-4166 240 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 1540000 Days•ng/mL | Geometric Coefficient of Variation 16.3 |
| MK-4166 240 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 2710000 Days•ng/mL | — |
| MK-4166 240 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 1870000 Days•ng/mL | — |
| MK-4166 340 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 2440000 Days•ng/mL | — |
| MK-4166 340 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 1160000 Days•ng/mL | Geometric Coefficient of Variation 56.1 |
| MK-4166 340 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 1260000 Days•ng/mL | Geometric Coefficient of Variation 23.3 |
| MK-4166 340 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 858000 Days•ng/mL | Geometric Coefficient of Variation 58.4 |
| MK-4166 480 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 1090000 Days•ng/mL | Geometric Coefficient of Variation 48.3 |
| MK-4166 480 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 1820000 Days•ng/mL | Geometric Coefficient of Variation 13.2 |
| MK-4166 480 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 707000 Days•ng/mL | Geometric Coefficient of Variation 148.2 |
| MK-4166 670 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 1620000 Days•ng/mL | Geometric Coefficient of Variation 27.2 |
| MK-4166 670 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 1820000 Days•ng/mL | Geometric Coefficient of Variation 0.2 |
| MK-4166 670 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 855000 Days•ng/mL | Geometric Coefficient of Variation 55.9 |
| MK-4166 670 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 931000 Days•ng/mL | Geometric Coefficient of Variation 38.4 |
| MK-4166 900 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 4 | 1730000 Days•ng/mL | Geometric Coefficient of Variation 112.9 |
| MK-4166 900 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 1 | 1130000 Days•ng/mL | Geometric Coefficient of Variation 68.7 |
| MK-4166 900 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 2 | 1470000 Days•ng/mL | Geometric Coefficient of Variation 57.8 |
| MK-4166 900 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time | Cycle 3 | 2340000 Days•ng/mL | Geometric Coefficient of Variation 55.1 |
Secondary
Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time
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.
Time frame: 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)
Population: All allocated participants who received ≥1 dose of pembrolizumab and had evaluable AUC0-last samples. Per protocol, %GCV values were not reported for cohorts with n\<2 participants, and MK-4166 monotherapy dose cohorts were not analyzed. Participants with samples that were hemolyzed or analyzed outside of stability were excluded from the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-4166 1.1 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 1550000 Days•ng/mL | — |
| MK-4166 1.1 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 466000 Days•ng/mL | Geometric Coefficient of Variation 258.9 |
| MK-4166 1.1 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 847000 Days•ng/mL | Geometric Coefficient of Variation 33.4 |
| MK-4166 1.1 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 587000 Days•ng/mL | Geometric Coefficient of Variation 36 |
| MK-4166 3.3 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 664000 Days•ng/mL | Geometric Coefficient of Variation 45 |
| MK-4166 3.3 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 490000 Days•ng/mL | — |
| MK-4166 3.3 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 515000 Days•ng/mL | Geometric Coefficient of Variation 43 |
| MK-4166 3.3 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 356000 Days•ng/mL | Geometric Coefficient of Variation 79.5 |
| MK-4166 10 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 304000 Days•ng/mL | — |
| MK-4166 10 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 398000 Days•ng/mL | Geometric Coefficient of Variation 14.3 |
| MK-4166 10 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 554000 Days•ng/mL | Geometric Coefficient of Variation 14 |
| MK-4166 10 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 321000 Days•ng/mL | Geometric Coefficient of Variation 125.7 |
| MK-4166 30 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 775000 Days•ng/mL | Geometric Coefficient of Variation 110.7 |
| MK-4166 30 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 663000 Days•ng/mL | Geometric Coefficient of Variation 16.1 |
| MK-4166 30 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 949000 Days•ng/mL | Geometric Coefficient of Variation 12.7 |
| MK-4166 30 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 998000 Days•ng/mL | Geometric Coefficient of Variation 4.5 |
| MK-4166 42 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 410000 Days•ng/mL | Geometric Coefficient of Variation 44.5 |
| MK-4166 42 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 98800 Days•ng/mL | Geometric Coefficient of Variation 96422.3 |
| MK-4166 42 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 603000 Days•ng/mL | Geometric Coefficient of Variation 64.7 |
| MK-4166 42 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 573000 Days•ng/mL | Geometric Coefficient of Variation 47.1 |
| MK-4166 59 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 491000 Days•ng/mL | Geometric Coefficient of Variation 39.9 |
| MK-4166 59 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 985000 Days•ng/mL | Geometric Coefficient of Variation 34.7 |
| MK-4166 59 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 938000 Days•ng/mL | Geometric Coefficient of Variation 6.3 |
| MK-4166 59 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 1120000 Days•ng/mL | Geometric Coefficient of Variation 72.3 |
| MK-4166 82 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 482000 Days•ng/mL | Geometric Coefficient of Variation 48.7 |
| MK-4166 82 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 454000 Days•ng/mL | Geometric Coefficient of Variation 20.5 |
| MK-4166 82 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 759000 Days•ng/mL | Geometric Coefficient of Variation 47.9 |
| MK-4166 120 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 567000 Days•ng/mL | Geometric Coefficient of Variation 62.3 |
| MK-4166 120 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 1020000 Days•ng/mL | Geometric Coefficient of Variation 33.7 |
| MK-4166 120 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 414000 Days•ng/mL | Geometric Coefficient of Variation 35.3 |
| MK-4166 120 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 747000 Days•ng/mL | Geometric Coefficient of Variation 32.3 |
| MK-4166 170 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 604000 Days•ng/mL | Geometric Coefficient of Variation 26.5 |
| MK-4166 170 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 766000 Days•ng/mL | Geometric Coefficient of Variation 18 |
| MK-4166 170 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 415000 Days•ng/mL | Geometric Coefficient of Variation 73.7 |
| MK-4166 240 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 663000 Days•ng/mL | Geometric Coefficient of Variation 9.5 |
| MK-4166 240 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 932000 Days•ng/mL | Geometric Coefficient of Variation 15.8 |
| MK-4166 240 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 1280000 Days•ng/mL | Geometric Coefficient of Variation 8 |
| MK-4166 240 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 455000 Days•ng/mL | Geometric Coefficient of Variation 192.8 |
| MK-4166 340 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 1410000 Days•ng/mL | — |
| MK-4166 340 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 873000 Days•ng/mL | Geometric Coefficient of Variation 14.4 |
| MK-4166 340 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 492000 Days•ng/mL | Geometric Coefficient of Variation 88.7 |
| MK-4166 340 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 549000 Days•ng/mL | Geometric Coefficient of Variation 18.7 |
| MK-4166 480 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 264000 Days•ng/mL | Geometric Coefficient of Variation 343.2 |
| MK-4166 480 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 389000 Days•ng/mL | Geometric Coefficient of Variation 162.2 |
| MK-4166 480 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 958000 Days•ng/mL | Geometric Coefficient of Variation 9.49 |
| MK-4166 670 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 284000 Days•ng/mL | Geometric Coefficient of Variation 95.5 |
| MK-4166 670 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 981000 Days•ng/mL | Geometric Coefficient of Variation 8.1 |
| MK-4166 670 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 1080000 Days•ng/mL | Geometric Coefficient of Variation 29.5 |
| MK-4166 670 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 416000 Days•ng/mL | Geometric Coefficient of Variation 119.9 |
| MK-4166 900 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 3 | 1080000 Days•ng/mL | Geometric Coefficient of Variation 33.4 |
| MK-4166 900 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 1 | 624000 Days•ng/mL | Geometric Coefficient of Variation 34.3 |
| MK-4166 900 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 4 | 664000 Days•ng/mL | Geometric Coefficient of Variation 132.9 |
| MK-4166 900 mg + Pembro | Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time | Cycle 2 | 635000 Days•ng/mL | Geometric Coefficient of Variation 78.4 |
Secondary
Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration
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.
Time frame: 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.
Population: All allocated participants who received at least 1 dose of MK-4166 and had evaluable flow cytometry data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MK-4166 0.0015 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 107.0 Percentage GITR receptor availability | — |
| MK-4166 0.0015 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 3 | 109.1 Percentage GITR receptor availability | — |
| MK-4166 0.0015 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 5 | 97.5 Percentage GITR receptor availability | — |
| MK-4166 0.0015 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 103.7 Percentage GITR receptor availability | — |
| MK-4166 0.0015 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; 2 hours Post Infusion | 102.5 Percentage GITR receptor availability | — |
| MK-4166 0.0015 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 100.2 Percentage GITR receptor availability | — |
| MK-4166 0.0015 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 106.0 Percentage GITR receptor availability | — |
| MK-4166 0.014 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 59.5 Percentage GITR receptor availability | — |
| MK-4166 0.014 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 5 | 107.1 Percentage GITR receptor availability | — |
| MK-4166 0.014 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 123.9 Percentage GITR receptor availability | — |
| MK-4166 0.014 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; 2 hours Post Infusion | 63.2 Percentage GITR receptor availability | — |
| MK-4166 0.014 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 52.8 Percentage GITR receptor availability | — |
| MK-4166 0.014 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 3 | 108.3 Percentage GITR receptor availability | — |
| MK-4166 0.014 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 103.4 Percentage GITR receptor availability | — |
| MK-4166 0.04 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 92.5 Percentage GITR receptor availability | — |
| MK-4166 0.04 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 122.9 Percentage GITR receptor availability | — |
| MK-4166 0.04 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 114.9 Percentage GITR receptor availability | — |
| MK-4166 0.04 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 5 | 111.6 Percentage GITR receptor availability | — |
| MK-4166 0.04 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 3 | 85.4 Percentage GITR receptor availability | — |
| MK-4166 0.04 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 114.9 Percentage GITR receptor availability | — |
| MK-4166 0.04 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 96.9 Percentage GITR receptor availability | — |
| MK-4166 0.04 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; 2 hours Post Infusion | 91.7 Percentage GITR receptor availability | — |
| MK-4166 0.12 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 3 | 72.4 Percentage GITR receptor availability | — |
| MK-4166 0.12 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 89.2 Percentage GITR receptor availability | — |
| MK-4166 0.12 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; 2 hours Post Infusion | 42.7 Percentage GITR receptor availability | — |
| MK-4166 0.12 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 92.2 Percentage GITR receptor availability | — |
| MK-4166 0.12 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 55.4 Percentage GITR receptor availability | — |
| MK-4166 0.12 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 51.9 Percentage GITR receptor availability | — |
| MK-4166 0.12 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 5 | 83.0 Percentage GITR receptor availability | — |
| MK-4166 0.12 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 94.8 Percentage GITR receptor availability | — |
| MK-4166 0.37 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 3 | 5.4 Percentage GITR receptor availability | — |
| MK-4166 0.37 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; 2 hours Post Infusion | 17.0 Percentage GITR receptor availability | — |
| MK-4166 0.37 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 15.0 Percentage GITR receptor availability | — |
| MK-4166 0.37 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 8.8 Percentage GITR receptor availability | — |
| MK-4166 0.37 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 5 | 8.8 Percentage GITR receptor availability | — |
| MK-4166 0.37 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 80.3 Percentage GITR receptor availability | — |
| MK-4166 0.37 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 74.8 Percentage GITR receptor availability | — |
| MK-4166 0.37 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 9.5 Percentage GITR receptor availability | — |
| MK-4166 1.1 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 2.2 Percentage GITR receptor availability | — |
| MK-4166 1.1 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 4.6 Percentage GITR receptor availability | — |
| MK-4166 1.1 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; 2 hours Post Infusion | 2.4 Percentage GITR receptor availability | — |
| MK-4166 1.1 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 71.4 Percentage GITR receptor availability | — |
| MK-4166 1.1 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 3 | 2.6 Percentage GITR receptor availability | — |
| MK-4166 1.1 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 5 | 1.7 Percentage GITR receptor availability | — |
| MK-4166 1.1 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 8.2 Percentage GITR receptor availability | — |
| MK-4166 10 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 84.8 Percentage GITR receptor availability | — |
| MK-4166 10 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 3 | 0.9 Percentage GITR receptor availability | — |
| MK-4166 10 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 5 | 4.5 Percentage GITR receptor availability | — |
| MK-4166 10 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 71.2 Percentage GITR receptor availability | — |
| MK-4166 10 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; 2 hours Post Infusion | 1.2 Percentage GITR receptor availability | — |
| MK-4166 10 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 3.0 Percentage GITR receptor availability | — |
| MK-4166 10 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 3.3 Percentage GITR receptor availability | — |
| MK-4166 30 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 49.3 Percentage GITR receptor availability | Standard Deviation 84.6 |
| MK-4166 30 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 46.2 Percentage GITR receptor availability | Standard Deviation 86.4 |
| MK-4166 30 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 26.3 Percentage GITR receptor availability | Standard Deviation 32 |
| MK-4166 30 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 3 | 50.0 Percentage GITR receptor availability | Standard Deviation 70.1 |
| MK-4166 30 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 169.3 Percentage GITR receptor availability | Standard Deviation 301.5 |
| MK-4166 30 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; 2 hours Post Infusion | 0.7 Percentage GITR receptor availability | — |
| MK-4166 30 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 148.6 Percentage GITR receptor availability | Standard Deviation 281.6 |
| MK-4166 42 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 15.2 Percentage GITR receptor availability | Standard Deviation 3 |
| MK-4166 42 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 2.2 Percentage GITR receptor availability | Standard Deviation 1.6 |
| MK-4166 42 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 10.8 Percentage GITR receptor availability | Standard Deviation 9.9 |
| MK-4166 42 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 57.1 Percentage GITR receptor availability | Standard Deviation 52.9 |
| MK-4166 42 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 5.8 Percentage GITR receptor availability | Standard Deviation 4.3 |
| MK-4166 59 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 9.1 Percentage GITR receptor availability | Standard Deviation 3.2 |
| MK-4166 59 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 67.4 Percentage GITR receptor availability | Standard Deviation 91.5 |
| MK-4166 59 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 4.8 Percentage GITR receptor availability | Standard Deviation 1 |
| MK-4166 59 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; 2 hours Post Infusion | 6.9 Percentage GITR receptor availability | — |
| MK-4166 59 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 6.3 Percentage GITR receptor availability | Standard Deviation 5.1 |
| MK-4166 59 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 3 | 4.3 Percentage GITR receptor availability | — |
| MK-4166 59 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 4.0 Percentage GITR receptor availability | — |
| MK-4166 82 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 17.4 Percentage GITR receptor availability | Standard Deviation 24.6 |
| MK-4166 82 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 40.9 Percentage GITR receptor availability | Standard Deviation 28.1 |
| MK-4166 82 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 7.6 Percentage GITR receptor availability | Standard Deviation 5.5 |
| MK-4166 82 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 10.0 Percentage GITR receptor availability | Standard Deviation 8.3 |
| MK-4166 82 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 4.2 Percentage GITR receptor availability | Standard Deviation 2.7 |
| MK-4166 120 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 6.5 Percentage GITR receptor availability | — |
| MK-4166 120 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 10.2 Percentage GITR receptor availability | Standard Deviation 3.6 |
| MK-4166 120 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 30.4 Percentage GITR receptor availability | Standard Deviation 34.6 |
| MK-4166 120 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 41.9 Percentage GITR receptor availability | Standard Deviation 4.7 |
| MK-4166 120 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 7.8 Percentage GITR receptor availability | Standard Deviation 3.8 |
| MK-4166 170 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 2.2 Percentage GITR receptor availability | Standard Deviation 0.4 |
| MK-4166 170 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 8.9 Percentage GITR receptor availability | Standard Deviation 13.8 |
| MK-4166 170 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 29.3 Percentage GITR receptor availability | Standard Deviation 28.1 |
| MK-4166 170 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 5.8 Percentage GITR receptor availability | Standard Deviation 5.2 |
| MK-4166 170 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 7.4 Percentage GITR receptor availability | Standard Deviation 5.9 |
| MK-4166 240 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 44.8 Percentage GITR receptor availability | Standard Deviation 62.4 |
| MK-4166 240 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 15.2 Percentage GITR receptor availability | Standard Deviation 15.9 |
| MK-4166 240 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 9.5 Percentage GITR receptor availability | Standard Deviation 6.5 |
| MK-4166 240 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 16.0 Percentage GITR receptor availability | Standard Deviation 9.4 |
| MK-4166 240 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 14.7 Percentage GITR receptor availability | Standard Deviation 7.1 |
| MK-4166 340 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 19.3 Percentage GITR receptor availability | Standard Deviation 15.3 |
| MK-4166 340 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 17.7 Percentage GITR receptor availability | Standard Deviation 5.7 |
| MK-4166 340 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 12.0 Percentage GITR receptor availability | Standard Deviation 8.9 |
| MK-4166 340 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 13.9 Percentage GITR receptor availability | Standard Deviation 3.4 |
| MK-4166 340 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 8.1 Percentage GITR receptor availability | Standard Deviation 6.7 |
| MK-4166 480 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 39.0 Percentage GITR receptor availability | Standard Deviation 50 |
| MK-4166 480 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 15.0 Percentage GITR receptor availability | Standard Deviation 9.8 |
| MK-4166 480 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 6.7 Percentage GITR receptor availability | Standard Deviation 2.6 |
| MK-4166 480 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 4.8 Percentage GITR receptor availability | Standard Deviation 2.7 |
| MK-4166 480 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 22.5 Percentage GITR receptor availability | Standard Deviation 12.6 |
| MK-4166 670 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 26.0 Percentage GITR receptor availability | — |
| MK-4166 670 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 77.0 Percentage GITR receptor availability | — |
| MK-4166 670 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 82.9 Percentage GITR receptor availability | — |
| MK-4166 670 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 65.8 Percentage GITR receptor availability | — |
| MK-4166 670 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 82.5 Percentage GITR receptor availability | — |
| MK-4166 900 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 7.0 Percentage GITR receptor availability | Standard Deviation 3.6 |
| MK-4166 900 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 15.5 Percentage GITR receptor availability | Standard Deviation 11.3 |
| MK-4166 900 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 15.5 Percentage GITR receptor availability | Standard Deviation 5.6 |
| MK-4166 900 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 14.4 Percentage GITR receptor availability | Standard Deviation 15.1 |
| MK-4166 900 mg | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 20.0 Percentage GITR receptor availability | Standard Deviation 10.7 |
| MK-4166 1.1 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; 2 hours Post Infusion | 4.9 Percentage GITR receptor availability | Standard Deviation 2.5 |
| MK-4166 1.1 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 10.2 Percentage GITR receptor availability | Standard Deviation 8.9 |
| MK-4166 1.1 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 109.9 Percentage GITR receptor availability | Standard Deviation 37.2 |
| MK-4166 1.1 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 39.9 Percentage GITR receptor availability | Standard Deviation 49.1 |
| MK-4166 1.1 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 6.1 Percentage GITR receptor availability | Standard Deviation 3.1 |
| MK-4166 1.1 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 3 | 7.2 Percentage GITR receptor availability | Standard Deviation 3.5 |
| MK-4166 1.1 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 6.9 Percentage GITR receptor availability | Standard Deviation 3.2 |
| MK-4166 3.3 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 74.1 Percentage GITR receptor availability | Standard Deviation 36.4 |
| MK-4166 3.3 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 3 | 2.4 Percentage GITR receptor availability | Standard Deviation 1.3 |
| MK-4166 3.3 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; 2 hours Post Infusion | 3.0 Percentage GITR receptor availability | Standard Deviation 2.1 |
| MK-4166 3.3 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 4.8 Percentage GITR receptor availability | Standard Deviation 1.8 |
| MK-4166 3.3 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 2.9 Percentage GITR receptor availability | Standard Deviation 2.3 |
| MK-4166 3.3 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 2.4 Percentage GITR receptor availability | Standard Deviation 0.3 |
| MK-4166 3.3 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 4.2 Percentage GITR receptor availability | Standard Deviation 1.5 |
| MK-4166 10 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; 2 hours Post Infusion | 8.1 Percentage GITR receptor availability | Standard Deviation 4.8 |
| MK-4166 10 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 8.8 Percentage GITR receptor availability | Standard Deviation 9.2 |
| MK-4166 10 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 5.4 Percentage GITR receptor availability | Standard Deviation 4.6 |
| MK-4166 10 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 7.3 Percentage GITR receptor availability | Standard Deviation 4 |
| MK-4166 10 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 3 | 3.9 Percentage GITR receptor availability | Standard Deviation 1.3 |
| MK-4166 10 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 70.0 Percentage GITR receptor availability | Standard Deviation 51.8 |
| MK-4166 10 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 7.3 Percentage GITR receptor availability | Standard Deviation 3.6 |
| MK-4166 30 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 12.8 Percentage GITR receptor availability | Standard Deviation 7.1 |
| MK-4166 30 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 7.6 Percentage GITR receptor availability | Standard Deviation 6.8 |
| MK-4166 30 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; 2 hours Post Infusion | 9.1 Percentage GITR receptor availability | — |
| MK-4166 30 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 7.1 Percentage GITR receptor availability | Standard Deviation 1.2 |
| MK-4166 30 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 3 | 1.6 Percentage GITR receptor availability | — |
| MK-4166 30 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 11.4 Percentage GITR receptor availability | Standard Deviation 8.7 |
| MK-4166 30 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 11.7 Percentage GITR receptor availability | Standard Deviation 7.9 |
| MK-4166 42 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 6.5 Percentage GITR receptor availability | Standard Deviation 0.2 |
| MK-4166 42 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 12.6 Percentage GITR receptor availability | Standard Deviation 6.9 |
| MK-4166 42 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 3.8 Percentage GITR receptor availability | Standard Deviation 1.8 |
| MK-4166 42 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 7.0 Percentage GITR receptor availability | Standard Deviation 2.6 |
| MK-4166 42 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 5.0 Percentage GITR receptor availability | Standard Deviation 4.3 |
| MK-4166 59 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 4.6 Percentage GITR receptor availability | Standard Deviation 2.3 |
| MK-4166 59 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 7.4 Percentage GITR receptor availability | Standard Deviation 2.2 |
| MK-4166 59 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 6.0 Percentage GITR receptor availability | Standard Deviation 4.9 |
| MK-4166 59 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 9.1 Percentage GITR receptor availability | Standard Deviation 4.8 |
| MK-4166 59 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 13.5 Percentage GITR receptor availability | — |
| MK-4166 82 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 51.2 Percentage GITR receptor availability | — |
| MK-4166 82 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 28.6 Percentage GITR receptor availability | — |
| MK-4166 82 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 19.9 Percentage GITR receptor availability | Standard Deviation 15.4 |
| MK-4166 82 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 6.7 Percentage GITR receptor availability | Standard Deviation 4.6 |
| MK-4166 82 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 9.3 Percentage GITR receptor availability | Standard Deviation 4.9 |
| MK-4166 120 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 8.3 Percentage GITR receptor availability | Standard Deviation 5.8 |
| MK-4166 120 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 8.6 Percentage GITR receptor availability | — |
| MK-4166 120 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 12.5 Percentage GITR receptor availability | — |
| MK-4166 170 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 4.0 Percentage GITR receptor availability | — |
| MK-4166 170 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 5.9 Percentage GITR receptor availability | Standard Deviation 0.9 |
| MK-4166 170 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 46.5 Percentage GITR receptor availability | Standard Deviation 54.5 |
| MK-4166 170 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 22.2 Percentage GITR receptor availability | — |
| MK-4166 170 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 7.3 Percentage GITR receptor availability | Standard Deviation 9.3 |
| MK-4166 240 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 11.8 Percentage GITR receptor availability | Standard Deviation 7 |
| MK-4166 240 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 3.8 Percentage GITR receptor availability | Standard Deviation 1.5 |
| MK-4166 240 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 13.0 Percentage GITR receptor availability | Standard Deviation 12.5 |
| MK-4166 240 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 11.4 Percentage GITR receptor availability | Standard Deviation 4.2 |
| MK-4166 240 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 8.8 Percentage GITR receptor availability | Standard Deviation 5.3 |
| MK-4166 340 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 26.8 Percentage GITR receptor availability | Standard Deviation 18.4 |
| MK-4166 340 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 40.8 Percentage GITR receptor availability | Standard Deviation 54.4 |
| MK-4166 340 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 12.0 Percentage GITR receptor availability | Standard Deviation 5.6 |
| MK-4166 340 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 23.0 Percentage GITR receptor availability | Standard Deviation 3.4 |
| MK-4166 340 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 55.5 Percentage GITR receptor availability | Standard Deviation 43.2 |
| MK-4166 480 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 26.0 Percentage GITR receptor availability | Standard Deviation 32.2 |
| MK-4166 480 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 22.5 Percentage GITR receptor availability | Standard Deviation 8.7 |
| MK-4166 480 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 8.0 Percentage GITR receptor availability | Standard Deviation 7.8 |
| MK-4166 480 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 28.4 Percentage GITR receptor availability | Standard Deviation 28.3 |
| MK-4166 480 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 3 | 9.9 Percentage GITR receptor availability | — |
| MK-4166 480 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 25.3 Percentage GITR receptor availability | Standard Deviation 3 |
| MK-4166 670 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 8.8 Percentage GITR receptor availability | — |
| MK-4166 670 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 13.7 Percentage GITR receptor availability | — |
| MK-4166 670 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 10.5 Percentage GITR receptor availability | Standard Deviation 8.9 |
| MK-4166 670 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 27.4 Percentage GITR receptor availability | Standard Deviation 19.2 |
| MK-4166 670 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 21.9 Percentage GITR receptor availability | Standard Deviation 17.6 |
| MK-4166 900 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 15 | 13.0 Percentage GITR receptor availability | Standard Deviation 14 |
| MK-4166 900 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1:Day 1; End of Infusion | 13.3 Percentage GITR receptor availability | Standard Deviation 17.4 |
| MK-4166 900 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 2 | 15.6 Percentage GITR receptor availability | Standard Deviation 20.8 |
| MK-4166 900 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 1: Day 8 | 11.3 Percentage GITR receptor availability | Standard Deviation 13.1 |
| MK-4166 900 mg + Pembro | Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration | Cycle 2: Day 1; Pre-dose | 9.2 Percentage GITR receptor availability | Standard Deviation 9.4 |
Secondary
Maximum Concentration (Cmax) of MK-4166 Over Time
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.
Time frame: 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)
Population: All allocated participants who received at least 1 dose of MK-4166 and had evaluable Cmax samples. Per protocol, %GCV values were not reported for cohorts with n\<2 participants. Participants with samples that were hemolyzed or analyzed outside of stability were excluded from the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-4166 0.0015 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 0.767 ng/mL | — |
| MK-4166 0.0015 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 0.536 ng/mL | — |
| MK-4166 0.0015 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 0.0225 ng/mL | — |
| MK-4166 0.0045 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 5.18 ng/mL | — |
| MK-4166 0.014 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 17.3 ng/mL | — |
| MK-4166 0.04 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 21.1 ng/mL | — |
| MK-4166 0.04 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 48.2 ng/mL | — |
| MK-4166 0.12 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 34.3 ng/mL | — |
| MK-4166 0.12 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 50.2 ng/mL | — |
| MK-4166 0.12 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 68.8 ng/mL | — |
| MK-4166 0.37 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 533 ng/mL | — |
| MK-4166 0.37 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 205 ng/mL | — |
| MK-4166 1.1 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 585 ng/mL | — |
| MK-4166 3.3 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 1580 ng/mL | — |
| MK-4166 3.3 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 1490 ng/mL | — |
| MK-4166 10 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 3550 ng/mL | — |
| MK-4166 10 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 179 ng/mL | — |
| MK-4166 10 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 607 ng/mL | — |
| MK-4166 30 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 10900 ng/mL | Geometric Coefficient of Variation 37.1 |
| MK-4166 30 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 8940 ng/mL | Geometric Coefficient of Variation 100.6 |
| MK-4166 30 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 11400 ng/mL | Geometric Coefficient of Variation 42 |
| MK-4166 42 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 4 | 7870 ng/mL | Geometric Coefficient of Variation 126.1 |
| MK-4166 42 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 13700 ng/mL | Geometric Coefficient of Variation 46.6 |
| MK-4166 42 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 12300 ng/mL | Geometric Coefficient of Variation 21.8 |
| MK-4166 42 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 13400 ng/mL | Geometric Coefficient of Variation 37.5 |
| MK-4166 59 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 21800 ng/mL | Geometric Coefficient of Variation 13.3 |
| MK-4166 59 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 4 | 13100 ng/mL | Geometric Coefficient of Variation 115.8 |
| MK-4166 59 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 14400 ng/mL | Geometric Coefficient of Variation 92.7 |
| MK-4166 59 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 16200 ng/mL | Geometric Coefficient of Variation 68.9 |
| MK-4166 82 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 23300 ng/mL | Geometric Coefficient of Variation 40.7 |
| MK-4166 82 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 29100 ng/mL | Geometric Coefficient of Variation 53.5 |
| MK-4166 82 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 4 | 20800 ng/mL | Geometric Coefficient of Variation 44.2 |
| MK-4166 82 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 31900 ng/mL | Geometric Coefficient of Variation 27.2 |
| MK-4166 120 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 4 | 38800 ng/mL | Geometric Coefficient of Variation 39.1 |
| MK-4166 120 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 77100 ng/mL | Geometric Coefficient of Variation 140.5 |
| MK-4166 120 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 42000 ng/mL | Geometric Coefficient of Variation 16.3 |
| MK-4166 120 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 38100 ng/mL | Geometric Coefficient of Variation 28.5 |
| MK-4166 170 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 58600 ng/mL | Geometric Coefficient of Variation 16.2 |
| MK-4166 170 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 51500 ng/mL | Geometric Coefficient of Variation 38.3 |
| MK-4166 170 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 4 | 67300 ng/mL | Geometric Coefficient of Variation 47.9 |
| MK-4166 170 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 52700 ng/mL | Geometric Coefficient of Variation 45.8 |
| MK-4166 240 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 115000 ng/mL | Geometric Coefficient of Variation 59.1 |
| MK-4166 240 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 68600 ng/mL | Geometric Coefficient of Variation 25.1 |
| MK-4166 240 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 4 | 88800 ng/mL | Geometric Coefficient of Variation 18.3 |
| MK-4166 240 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 88700 ng/mL | Geometric Coefficient of Variation 11.8 |
| MK-4166 340 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 4 | 86800 ng/mL | Geometric Coefficient of Variation 28.8 |
| MK-4166 340 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 96500 ng/mL | Geometric Coefficient of Variation 25.8 |
| MK-4166 340 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 120000 ng/mL | Geometric Coefficient of Variation 59.2 |
| MK-4166 340 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 115000 ng/mL | Geometric Coefficient of Variation 49.4 |
| MK-4166 480 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 168000 ng/mL | Geometric Coefficient of Variation 20 |
| MK-4166 480 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 149000 ng/mL | Geometric Coefficient of Variation 16.6 |
| MK-4166 480 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 147000 ng/mL | — |
| MK-4166 670 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 4 | 256000 ng/mL | — |
| MK-4166 670 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 247000 ng/mL | — |
| MK-4166 670 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 228000 ng/mL | Geometric Coefficient of Variation 45.7 |
| MK-4166 670 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 195000 ng/mL | Geometric Coefficient of Variation 44.4 |
| MK-4166 900 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 389000 ng/mL | Geometric Coefficient of Variation 24.4 |
| MK-4166 900 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 301000 ng/mL | Geometric Coefficient of Variation 18.8 |
| MK-4166 900 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 4 | 501000 ng/mL | — |
| MK-4166 900 mg | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 364000 ng/mL | Geometric Coefficient of Variation 33.5 |
| MK-4166 1.1 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 1790 ng/mL | Geometric Coefficient of Variation 16.6 |
| MK-4166 1.1 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 803 ng/mL | Geometric Coefficient of Variation 26.2 |
| MK-4166 1.1 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 660 ng/mL | Geometric Coefficient of Variation 46.3 |
| MK-4166 1.1 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 4 | 42.9 ng/mL | — |
| MK-4166 3.3 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 3600 ng/mL | Geometric Coefficient of Variation 361.8 |
| MK-4166 3.3 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 4010 ng/mL | Geometric Coefficient of Variation 11.4 |
| MK-4166 3.3 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 3670 ng/mL | Geometric Coefficient of Variation 72.9 |
| MK-4166 10 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 541 ng/mL | Geometric Coefficient of Variation 31149.1 |
| MK-4166 10 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 4 | 10400 ng/mL | — |
| MK-4166 10 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 2190 ng/mL | Geometric Coefficient of Variation 263.1 |
| MK-4166 10 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 5010 ng/mL | Geometric Coefficient of Variation 39.7 |
| MK-4166 30 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 16300 ng/mL | Geometric Coefficient of Variation 32.2 |
| MK-4166 30 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 4 | 14200 ng/mL | Geometric Coefficient of Variation 48 |
| MK-4166 30 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 18800 ng/mL | Geometric Coefficient of Variation 41.8 |
| MK-4166 30 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 18500 ng/mL | Geometric Coefficient of Variation 17.5 |
| MK-4166 42 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 17900 ng/mL | Geometric Coefficient of Variation 52.5 |
| MK-4166 42 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 16900 ng/mL | Geometric Coefficient of Variation 51.1 |
| MK-4166 42 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 4 | 16900 ng/mL | Geometric Coefficient of Variation 110.1 |
| MK-4166 42 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 17400 ng/mL | Geometric Coefficient of Variation 72.1 |
| MK-4166 59 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 30300 ng/mL | Geometric Coefficient of Variation 11 |
| MK-4166 59 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 20400 ng/mL | Geometric Coefficient of Variation 5.75 |
| MK-4166 59 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 27900 ng/mL | Geometric Coefficient of Variation 7.4 |
| MK-4166 59 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 4 | 26600 ng/mL | Geometric Coefficient of Variation 12.3 |
| MK-4166 82 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 32500 ng/mL | Geometric Coefficient of Variation 36.2 |
| MK-4166 82 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 26300 ng/mL | Geometric Coefficient of Variation 32.1 |
| MK-4166 82 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 37300 ng/mL | Geometric Coefficient of Variation 23.4 |
| MK-4166 120 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 4 | 40600 ng/mL | Geometric Coefficient of Variation 43.7 |
| MK-4166 120 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 28300 ng/mL | Geometric Coefficient of Variation 44.5 |
| MK-4166 120 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 38100 ng/mL | Geometric Coefficient of Variation 25.6 |
| MK-4166 120 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 48800 ng/mL | Geometric Coefficient of Variation 45.6 |
| MK-4166 170 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 65000 ng/mL | Geometric Coefficient of Variation 20.7 |
| MK-4166 170 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 96800 ng/mL | Geometric Coefficient of Variation 62.8 |
| MK-4166 170 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 4 | 43200 ng/mL | — |
| MK-4166 170 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 55200 ng/mL | Geometric Coefficient of Variation 17.2 |
| MK-4166 240 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 105000 ng/mL | Geometric Coefficient of Variation 21.6 |
| MK-4166 240 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 111000 ng/mL | Geometric Coefficient of Variation 20.6 |
| MK-4166 240 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 4 | 126000 ng/mL | Geometric Coefficient of Variation 42.5 |
| MK-4166 240 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 85900 ng/mL | Geometric Coefficient of Variation 12.7 |
| MK-4166 340 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 117000 ng/mL | Geometric Coefficient of Variation 35.7 |
| MK-4166 340 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 109000 ng/mL | Geometric Coefficient of Variation 8.9 |
| MK-4166 340 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 4 | 207000 ng/mL | — |
| MK-4166 340 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 118000 ng/mL | Geometric Coefficient of Variation 14.7 |
| MK-4166 480 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 144000 ng/mL | Geometric Coefficient of Variation 2.8 |
| MK-4166 480 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 193000 ng/mL | Geometric Coefficient of Variation 18.1 |
| MK-4166 480 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 175000 ng/mL | Geometric Coefficient of Variation 3.2 |
| MK-4166 670 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 271000 ng/mL | Geometric Coefficient of Variation 8.1 |
| MK-4166 670 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 321000 ng/mL | Geometric Coefficient of Variation 19.3 |
| MK-4166 670 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 210000 ng/mL | Geometric Coefficient of Variation 11.8 |
| MK-4166 670 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 4 | 318000 ng/mL | Geometric Coefficient of Variation 2 |
| MK-4166 900 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 1 | 234000 ng/mL | Geometric Coefficient of Variation 22.7 |
| MK-4166 900 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 3 | 333000 ng/mL | Geometric Coefficient of Variation 22.4 |
| MK-4166 900 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 2 | 231000 ng/mL | Geometric Coefficient of Variation 173.3 |
| MK-4166 900 mg + Pembro | Maximum Concentration (Cmax) of MK-4166 Over Time | Cycle 4 | 386000 ng/mL | Geometric Coefficient of Variation 22 |
Secondary
Maximum Concentration (Cmax) of Pembrolizumab Over Time
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.
Time frame: 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)
Population: All allocated participants who received ≥1 dose of pembrolizumab and had evaluable Cmax samples. Per protocol, %GCV values were not reported for cohorts with n\<2 participants, and MK-4166 monotherapy dose cohorts were not analyzed. Participants with samples that were hemolyzed or analyzed outside of stability were excluded from the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-4166 1.1 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 1 | 82400 ng/mL | Geometric Coefficient of Variation 27.9 |
| MK-4166 1.1 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 3 | 97200 ng/mL | Geometric Coefficient of Variation 56.3 |
| MK-4166 1.1 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 2 | 90000 ng/mL | Geometric Coefficient of Variation 32.2 |
| MK-4166 1.1 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 4 | 156000 ng/mL | — |
| MK-4166 3.3 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 3 | 78400 ng/mL | Geometric Coefficient of Variation 31.7 |
| MK-4166 3.3 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 4 | 54700 ng/mL | — |
| MK-4166 3.3 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 2 | 76800 ng/mL | Geometric Coefficient of Variation 31.8 |
| MK-4166 3.3 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 1 | 68500 ng/mL | Geometric Coefficient of Variation 32.4 |
| MK-4166 10 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 4 | 57000 ng/mL | — |
| MK-4166 10 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 3 | 61600 ng/mL | Geometric Coefficient of Variation 22.9 |
| MK-4166 10 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 1 | 51700 ng/mL | Geometric Coefficient of Variation 25.7 |
| MK-4166 10 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 2 | 61300 ng/mL | Geometric Coefficient of Variation 17.2 |
| MK-4166 30 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 3 | 97200 ng/mL | Geometric Coefficient of Variation 18.7 |
| MK-4166 30 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 2 | 16200 ng/mL | Geometric Coefficient of Variation 109.6 |
| MK-4166 30 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 4 | 105000 ng/mL | Geometric Coefficient of Variation 17.2 |
| MK-4166 30 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 1 | 81700 ng/mL | Geometric Coefficient of Variation 17.2 |
| MK-4166 42 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 4 | 96500 ng/mL | Geometric Coefficient of Variation 31.6 |
| MK-4166 42 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 3 | 73000 ng/mL | Geometric Coefficient of Variation 56.8 |
| MK-4166 42 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 2 | 73000 ng/mL | Geometric Coefficient of Variation 35.9 |
| MK-4166 42 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 1 | 57600 ng/mL | Geometric Coefficient of Variation 35.7 |
| MK-4166 59 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 3 | 115000 ng/mL | Geometric Coefficient of Variation 9.2 |
| MK-4166 59 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 1 | 78400 ng/mL | Geometric Coefficient of Variation 18.4 |
| MK-4166 59 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 4 | 125000 ng/mL | Geometric Coefficient of Variation 7.9 |
| MK-4166 59 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 2 | 96800 ng/mL | Geometric Coefficient of Variation 14.2 |
| MK-4166 82 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 1 | 72600 ng/mL | Geometric Coefficient of Variation 24.3 |
| MK-4166 82 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 2 | 85700 ng/mL | Geometric Coefficient of Variation 40.7 |
| MK-4166 82 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 3 | 93100 ng/mL | Geometric Coefficient of Variation 33.8 |
| MK-4166 120 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 3 | 79100 ng/mL | Geometric Coefficient of Variation 38.7 |
| MK-4166 120 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 2 | 48700 ng/mL | Geometric Coefficient of Variation 79.3 |
| MK-4166 120 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 4 | 83500 ng/mL | Geometric Coefficient of Variation 57.6 |
| MK-4166 120 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 1 | 57700 ng/mL | Geometric Coefficient of Variation 27.2 |
| MK-4166 170 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 1 | 63300 ng/mL | Geometric Coefficient of Variation 30.7 |
| MK-4166 170 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 3 | 83200 ng/mL | Geometric Coefficient of Variation 22.8 |
| MK-4166 170 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 2 | 78500 ng/mL | Geometric Coefficient of Variation 12.5 |
| MK-4166 240 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 1 | 83700 ng/mL | Geometric Coefficient of Variation 24.8 |
| MK-4166 240 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 2 | 82300 ng/mL | Geometric Coefficient of Variation 25.5 |
| MK-4166 240 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 4 | 90800 ng/mL | Geometric Coefficient of Variation 47.7 |
| MK-4166 240 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 3 | 76000 ng/mL | Geometric Coefficient of Variation 52.2 |
| MK-4166 340 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 4 | 143000 ng/mL | — |
| MK-4166 340 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 3 | 93200 ng/mL | Geometric Coefficient of Variation 13.7 |
| MK-4166 340 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 2 | 86000 ng/mL | Geometric Coefficient of Variation 17.4 |
| MK-4166 340 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 1 | 66900 ng/mL | Geometric Coefficient of Variation 4.1 |
| MK-4166 480 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 3 | 115000 ng/mL | Geometric Coefficient of Variation 11.7 |
| MK-4166 480 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 2 | 96600 ng/mL | Geometric Coefficient of Variation 4.9 |
| MK-4166 480 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 1 | 81600 ng/mL | Geometric Coefficient of Variation 22.5 |
| MK-4166 670 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 2 | 94100 ng/mL | Geometric Coefficient of Variation 12.9 |
| MK-4166 670 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 3 | 94100 ng/mL | Geometric Coefficient of Variation 7.1 |
| MK-4166 670 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 1 | 70400 ng/mL | Geometric Coefficient of Variation 15.1 |
| MK-4166 670 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 4 | 95600 ng/mL | Geometric Coefficient of Variation 4.66 |
| MK-4166 900 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 4 | 97400 ng/mL | Geometric Coefficient of Variation 23.9 |
| MK-4166 900 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 1 | 69900 ng/mL | Geometric Coefficient of Variation 20.9 |
| MK-4166 900 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 2 | 80100 ng/mL | Geometric Coefficient of Variation 25.4 |
| MK-4166 900 mg + Pembro | Maximum Concentration (Cmax) of Pembrolizumab Over Time | Cycle 3 | 94600 ng/mL | Geometric Coefficient of Variation 17.3 |
Secondary
Terminal Half-Life (t ½) of MK-4166 Over Time
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.
Time frame: 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)
Population: All allocated participants who received at least 1 dose of MK-4166 and had evaluable t½ samples. Per protocol, %GCV values were not reported for cohorts with n\<2 participants. Participants with samples that were hemolyzed or analyzed outside of stability were excluded from the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-4166 0.0015 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 2.61 Days | — |
| MK-4166 0.0015 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | NA Days | — |
| MK-4166 0.0015 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 3.34 Days | — |
| MK-4166 0.0045 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 2.74 Days | — |
| MK-4166 0.014 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 2.68 Days | — |
| MK-4166 0.04 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 2.31 Days | — |
| MK-4166 0.04 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 3.48 Days | — |
| MK-4166 0.12 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 1.76 Days | — |
| MK-4166 0.12 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 2.73 Days | — |
| MK-4166 0.12 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 3.22 Days | — |
| MK-4166 0.37 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 2.10 Days | — |
| MK-4166 0.37 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 3.42 Days | — |
| MK-4166 1.1 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 3.39 Days | — |
| MK-4166 3.3 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 1.88 Days | — |
| MK-4166 3.3 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 3.30 Days | — |
| MK-4166 10 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | NA Days | — |
| MK-4166 10 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 7.62 Days | — |
| MK-4166 10 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | NA Days | — |
| MK-4166 30 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 4.53 Days | Geometric Coefficient of Variation 171.6 |
| MK-4166 30 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 7.7 Days | Geometric Coefficient of Variation 67.2 |
| MK-4166 30 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 3.11 Days | Geometric Coefficient of Variation 120.5 |
| MK-4166 42 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 4.52 Days | Geometric Coefficient of Variation 376.5 |
| MK-4166 42 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 4 | 2.04 Days | Geometric Coefficient of Variation 706.9 |
| MK-4166 42 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 7.21 Days | Geometric Coefficient of Variation 167.8 |
| MK-4166 42 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 7.49 Days | Geometric Coefficient of Variation 107.2 |
| MK-4166 59 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 4 | 8.79 Days | — |
| MK-4166 59 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 1.31 Days | Geometric Coefficient of Variation 2100.9 |
| MK-4166 59 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 11.9 Days | — |
| MK-4166 59 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 2.93 Days | Geometric Coefficient of Variation 85.2 |
| MK-4166 82 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 9.95 Days | Geometric Coefficient of Variation 38.4 |
| MK-4166 82 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 4 | 2.59 Days | Geometric Coefficient of Variation 220.3 |
| MK-4166 82 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 12.8 Days | Geometric Coefficient of Variation 27.6 |
| MK-4166 82 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 6.54 Days | Geometric Coefficient of Variation 54 |
| MK-4166 120 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 6.37 Days | Geometric Coefficient of Variation 87.7 |
| MK-4166 120 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 9.59 Days | Geometric Coefficient of Variation 44.8 |
| MK-4166 120 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 5.82 Days | Geometric Coefficient of Variation 65.6 |
| MK-4166 120 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 4 | NA Days | — |
| MK-4166 170 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 3.61 Days | Geometric Coefficient of Variation 787.8 |
| MK-4166 170 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 7.66 Days | Geometric Coefficient of Variation 31.4 |
| MK-4166 170 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 4 | 7.43 Days | Geometric Coefficient of Variation 139.3 |
| MK-4166 170 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 8.97 Days | Geometric Coefficient of Variation 39.5 |
| MK-4166 240 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 5.17 Days | Geometric Coefficient of Variation 126.5 |
| MK-4166 240 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 11.9 Days | Geometric Coefficient of Variation 12.4 |
| MK-4166 240 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 11.4 Days | Geometric Coefficient of Variation 123.7 |
| MK-4166 240 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 4 | 8.14 Days | Geometric Coefficient of Variation 11.5 |
| MK-4166 340 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 13.1 Days | Geometric Coefficient of Variation 32.8 |
| MK-4166 340 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 4 | 17.8 Days | — |
| MK-4166 340 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 12.0 Days | Geometric Coefficient of Variation 69.2 |
| MK-4166 340 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 11.9 Days | Geometric Coefficient of Variation 29.2 |
| MK-4166 480 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 11.3 Days | — |
| MK-4166 480 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 11.3 Days | Geometric Coefficient of Variation 22.7 |
| MK-4166 480 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 10.2 Days | Geometric Coefficient of Variation 13 |
| MK-4166 670 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 11.2 Days | Geometric Coefficient of Variation 49.6 |
| MK-4166 670 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 13.1 Days | Geometric Coefficient of Variation 37.2 |
| MK-4166 670 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 10.4 Days | — |
| MK-4166 670 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 4 | 3.91 Days | — |
| MK-4166 900 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 12.3 Days | Geometric Coefficient of Variation 4.5 |
| MK-4166 900 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 21.4 Days | Geometric Coefficient of Variation 60 |
| MK-4166 900 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 4 | NA Days | — |
| MK-4166 900 mg | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 14.1 Days | Geometric Coefficient of Variation 36.7 |
| MK-4166 1.1 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 2.86 Days | Geometric Coefficient of Variation 9.63 |
| MK-4166 1.1 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 3.74 Days | Geometric Coefficient of Variation 486.6 |
| MK-4166 1.1 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 4 | NA Days | — |
| MK-4166 1.1 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 2.19 Days | Geometric Coefficient of Variation 394 |
| MK-4166 3.3 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 1.38 Days | Geometric Coefficient of Variation 158.1 |
| MK-4166 3.3 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 3.72 Days | Geometric Coefficient of Variation 88.5 |
| MK-4166 3.3 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 3.64 Days | Geometric Coefficient of Variation 27.7 |
| MK-4166 10 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 6.15 Days | Geometric Coefficient of Variation 78.5 |
| MK-4166 10 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 4.55 Days | Geometric Coefficient of Variation 318 |
| MK-4166 10 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 4 | 7.12 Days | — |
| MK-4166 10 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 16.6 Days | — |
| MK-4166 30 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 4 | 6.68 Days | Geometric Coefficient of Variation 103.1 |
| MK-4166 30 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 10.5 Days | Geometric Coefficient of Variation 62.9 |
| MK-4166 30 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 12.0 Days | Geometric Coefficient of Variation 60.9 |
| MK-4166 30 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 10.4 Days | Geometric Coefficient of Variation 95 |
| MK-4166 42 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 6.92 Days | Geometric Coefficient of Variation 82 |
| MK-4166 42 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 7.31 Days | Geometric Coefficient of Variation 48.9 |
| MK-4166 42 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 7.32 Days | Geometric Coefficient of Variation 92.3 |
| MK-4166 42 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 4 | 13.1 Days | — |
| MK-4166 59 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 5.10 Days | Geometric Coefficient of Variation 23.4 |
| MK-4166 59 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 8.60 Days | Geometric Coefficient of Variation 66.6 |
| MK-4166 59 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 4 | 6.27 Days | Geometric Coefficient of Variation 8.1 |
| MK-4166 59 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 5.82 Days | Geometric Coefficient of Variation 33.3 |
| MK-4166 82 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 11.7 Days | Geometric Coefficient of Variation 14.3 |
| MK-4166 82 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 8.84 Days | Geometric Coefficient of Variation 14.3 |
| MK-4166 82 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 7.91 Days | Geometric Coefficient of Variation 23.9 |
| MK-4166 120 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 9.22 Days | Geometric Coefficient of Variation 106 |
| MK-4166 120 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 10.9 Days | Geometric Coefficient of Variation 28.8 |
| MK-4166 120 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 4 | 13.8 Days | Geometric Coefficient of Variation 34.5 |
| MK-4166 120 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 9.97 Days | Geometric Coefficient of Variation 30.5 |
| MK-4166 170 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 12.3 Days | Geometric Coefficient of Variation 46.1 |
| MK-4166 170 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 4 | 14.8 Days | — |
| MK-4166 170 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 11.9 Days | Geometric Coefficient of Variation 12 |
| MK-4166 170 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 12.4 Days | Geometric Coefficient of Variation 36.6 |
| MK-4166 240 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 13.0 Days | Geometric Coefficient of Variation 10.6 |
| MK-4166 240 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 15.7 Days | Geometric Coefficient of Variation 10.9 |
| MK-4166 240 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 4 | 16.4 Days | Geometric Coefficient of Variation 27.6 |
| MK-4166 240 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 22.1 Days | Geometric Coefficient of Variation 50.8 |
| MK-4166 340 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 7.43 Days | Geometric Coefficient of Variation 111.8 |
| MK-4166 340 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 4 | 13.0 Days | — |
| MK-4166 340 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 7.81 Days | Geometric Coefficient of Variation 120 |
| MK-4166 340 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 5.75 Days | Geometric Coefficient of Variation 269.1 |
| MK-4166 480 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 17.6 Days | — |
| MK-4166 480 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 11.7 Days | Geometric Coefficient of Variation 12.3 |
| MK-4166 480 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 13.4 Days | Geometric Coefficient of Variation 37.4 |
| MK-4166 670 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 16.2 Days | Geometric Coefficient of Variation 5.36 |
| MK-4166 670 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 4 | 12.0 Days | — |
| MK-4166 670 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 15.7 Days | Geometric Coefficient of Variation 18.6 |
| MK-4166 670 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 9.03 Days | Geometric Coefficient of Variation 77.4 |
| MK-4166 900 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 2 | 13.2 Days | Geometric Coefficient of Variation 56.4 |
| MK-4166 900 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 4 | 17.2 Days | Geometric Coefficient of Variation 48.6 |
| MK-4166 900 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 3 | 21.6 Days | Geometric Coefficient of Variation 85.4 |
| MK-4166 900 mg + Pembro | Terminal Half-Life (t ½) of MK-4166 Over Time | Cycle 1 | 12.0 Days | Geometric Coefficient of Variation 70.1 |
Secondary
Terminal Half-Life (t ½) of Pembrolizumab Over Time
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.
Time frame: 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)
Population: All allocated participants who received ≥1 dose of pembrolizumab and had evaluable t½ samples. Per protocol, %GCV values were not reported for cohorts with n\<2 participants, and MK-4166 monotherapy dose cohorts were not analyzed. Participants with samples that were hemolyzed or analyzed outside of stability were excluded from the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-4166 1.1 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 2 | 16.8 Days | Geometric Coefficient of Variation 30.6 |
| MK-4166 1.1 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 1 | 17.2 Days | Geometric Coefficient of Variation 21.8 |
| MK-4166 1.1 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 4 | 17.7 Days | — |
| MK-4166 1.1 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 3 | 14.0 Days | Geometric Coefficient of Variation 59.2 |
| MK-4166 3.3 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 1 | 12.1 Days | Geometric Coefficient of Variation 80.3 |
| MK-4166 3.3 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 3 | 10.5 Days | Geometric Coefficient of Variation 42.1 |
| MK-4166 3.3 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 2 | 21.1 Days | Geometric Coefficient of Variation 22.4 |
| MK-4166 3.3 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 4 | 11.1 Days | — |
| MK-4166 10 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 3 | 14.6 Days | Geometric Coefficient of Variation 39.4 |
| MK-4166 10 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 2 | 10 Days | Geometric Coefficient of Variation 189.6 |
| MK-4166 10 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 1 | 14.7 Days | Geometric Coefficient of Variation 32.7 |
| MK-4166 10 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 4 | 10.5 Days | — |
| MK-4166 30 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 4 | 18.0 Days | Geometric Coefficient of Variation 117.5 |
| MK-4166 30 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 1 | 23.5 Days | Geometric Coefficient of Variation 54.4 |
| MK-4166 30 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 2 | 18.5 Days | Geometric Coefficient of Variation 13.4 |
| MK-4166 30 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 3 | 15.2 Days | Geometric Coefficient of Variation 49.2 |
| MK-4166 42 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 1 | 11.8 Days | Geometric Coefficient of Variation 46.4 |
| MK-4166 42 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 2 | 14.4 Days | Geometric Coefficient of Variation 42.1 |
| MK-4166 42 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 3 | 15.0 Days | Geometric Coefficient of Variation 122.9 |
| MK-4166 42 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 4 | 34.1 Days | — |
| MK-4166 59 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 3 | 14.8 Days | Geometric Coefficient of Variation 5.7 |
| MK-4166 59 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 1 | 9.45 Days | Geometric Coefficient of Variation 61.8 |
| MK-4166 59 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 2 | 16.0 Days | Geometric Coefficient of Variation 4.4 |
| MK-4166 59 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 4 | 14.9 Days | — |
| MK-4166 82 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 1 | 10.9 Days | Geometric Coefficient of Variation 43.5 |
| MK-4166 82 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 3 | 9.45 Days | Geometric Coefficient of Variation 35.3 |
| MK-4166 82 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 2 | 15.0 Days | Geometric Coefficient of Variation 9.17 |
| MK-4166 120 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 3 | 20.8 Days | Geometric Coefficient of Variation 15.4 |
| MK-4166 120 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 2 | 18.6 Days | Geometric Coefficient of Variation 38.1 |
| MK-4166 120 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 4 | 23.3 Days | Geometric Coefficient of Variation 38.1 |
| MK-4166 120 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 1 | 17.7 Days | Geometric Coefficient of Variation 23.1 |
| MK-4166 170 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 2 | 12.7 Days | Geometric Coefficient of Variation 22.4 |
| MK-4166 170 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 3 | 9.38 Days | Geometric Coefficient of Variation 6.03 |
| MK-4166 170 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 1 | 11.3 Days | Geometric Coefficient of Variation 22.9 |
| MK-4166 240 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 4 | 22.4 Days | — |
| MK-4166 240 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 2 | 15.7 Days | Geometric Coefficient of Variation 9.65 |
| MK-4166 240 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 1 | 16.1 Days | Geometric Coefficient of Variation 27.6 |
| MK-4166 240 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 3 | 13.3 Days | — |
| MK-4166 340 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 4 | 15.7 Days | — |
| MK-4166 340 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 2 | 13.7 Days | Geometric Coefficient of Variation 18.6 |
| MK-4166 340 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 1 | 13.2 Days | Geometric Coefficient of Variation 63.6 |
| MK-4166 340 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 3 | 11.3 Days | Geometric Coefficient of Variation 45.2 |
| MK-4166 480 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 1 | 8.84 Days | Geometric Coefficient of Variation 189.6 |
| MK-4166 480 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 2 | 18.9 Days | Geometric Coefficient of Variation 1.03 |
| MK-4166 480 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 3 | 8.11 Days | Geometric Coefficient of Variation 63.8 |
| MK-4166 670 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 3 | 19.8 Days | Geometric Coefficient of Variation 11.1 |
| MK-4166 670 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 4 | 6.94 Days | Geometric Coefficient of Variation 34.8 |
| MK-4166 670 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 2 | 17.6 Days | Geometric Coefficient of Variation 35.9 |
| MK-4166 670 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 1 | 11.2 Days | Geometric Coefficient of Variation 64.2 |
| MK-4166 900 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 2 | 16.7 Days | Geometric Coefficient of Variation 55.1 |
| MK-4166 900 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 1 | 19.0 Days | Geometric Coefficient of Variation 54.1 |
| MK-4166 900 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 4 | 16.6 Days | Geometric Coefficient of Variation 109.6 |
| MK-4166 900 mg + Pembro | Terminal Half-Life (t ½) of Pembrolizumab Over Time | Cycle 3 | 24.9 Days | Geometric Coefficient of Variation 57.4 |
Secondary
Time to Maximum Concentration (Tmax) of MK-4166 Over Time
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.
Time frame: 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)
Population: All allocated participants who received at least 1 dose of MK-4166 and had evaluable Tmax samples. Participants with samples that were hemolyzed or analyzed outside of stability were excluded from the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MK-4166 0.0015 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 6.98 Days |
| MK-4166 0.0015 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.96 Days |
| MK-4166 0.0015 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.08 Days |
| MK-4166 0.0045 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.03 Days |
| MK-4166 0.014 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.03 Days |
| MK-4166 0.04 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.03 Days |
| MK-4166 0.04 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.03 Days |
| MK-4166 0.12 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.04 Days |
| MK-4166 0.12 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.03 Days |
| MK-4166 0.12 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.04 Days |
| MK-4166 0.37 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.03 Days |
| MK-4166 0.37 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.02 Days |
| MK-4166 1.1 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.08 Days |
| MK-4166 3.3 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.02 Days |
| MK-4166 3.3 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.02 Days |
| MK-4166 10 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.03 Days |
| MK-4166 10 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.08 Days |
| MK-4166 10 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.03 Days |
| MK-4166 30 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.05 Days |
| MK-4166 30 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.03 Days |
| MK-4166 30 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.03 Days |
| MK-4166 42 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 4 | 0.06 Days |
| MK-4166 42 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.02 Days |
| MK-4166 42 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.03 Days |
| MK-4166 42 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.03 Days |
| MK-4166 59 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.02 Days |
| MK-4166 59 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.05 Days |
| MK-4166 59 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.05 Days |
| MK-4166 59 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 4 | 0.03 Days |
| MK-4166 82 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.03 Days |
| MK-4166 82 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 4 | 0.02 Days |
| MK-4166 82 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.02 Days |
| MK-4166 82 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.03 Days |
| MK-4166 120 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.02 Days |
| MK-4166 120 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.03 Days |
| MK-4166 120 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 4 | 0.05 Days |
| MK-4166 120 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.02 Days |
| MK-4166 170 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 4 | 0.02 Days |
| MK-4166 170 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.07 Days |
| MK-4166 170 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.03 Days |
| MK-4166 170 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.02 Days |
| MK-4166 240 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.47 Days |
| MK-4166 240 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 4 | 0.03 Days |
| MK-4166 240 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.08 Days |
| MK-4166 240 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.03 Days |
| MK-4166 340 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.08 Days |
| MK-4166 340 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.02 Days |
| MK-4166 340 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.02 Days |
| MK-4166 340 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 4 | 0.06 Days |
| MK-4166 480 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.03 Days |
| MK-4166 480 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.08 Days |
| MK-4166 480 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.03 Days |
| MK-4166 670 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.02 Days |
| MK-4166 670 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.02 Days |
| MK-4166 670 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.02 Days |
| MK-4166 670 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 4 | 0.02 Days |
| MK-4166 900 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.08 Days |
| MK-4166 900 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.02 Days |
| MK-4166 900 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.02 Days |
| MK-4166 900 mg | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 4 | 0.02 Days |
| MK-4166 1.1 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 4 | 0.03 Days |
| MK-4166 1.1 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.03 Days |
| MK-4166 1.1 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.03 Days |
| MK-4166 1.1 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.03 Days |
| MK-4166 3.3 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.03 Days |
| MK-4166 3.3 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.03 Days |
| MK-4166 3.3 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.03 Days |
| MK-4166 10 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.02 Days |
| MK-4166 10 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.08 Days |
| MK-4166 10 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 4 | 0.09 Days |
| MK-4166 10 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.06 Days |
| MK-4166 30 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.08 Days |
| MK-4166 30 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.02 Days |
| MK-4166 30 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.02 Days |
| MK-4166 30 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 4 | 0.08 Days |
| MK-4166 42 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.02 Days |
| MK-4166 42 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.08 Days |
| MK-4166 42 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.08 Days |
| MK-4166 42 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 4 | 0.05 Days |
| MK-4166 59 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.03 Days |
| MK-4166 59 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.03 Days |
| MK-4166 59 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 4 | 0.02 Days |
| MK-4166 59 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.05 Days |
| MK-4166 82 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.03 Days |
| MK-4166 82 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.08 Days |
| MK-4166 82 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.04 Days |
| MK-4166 120 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.03 Days |
| MK-4166 120 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 4 | 0.08 Days |
| MK-4166 120 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.02 Days |
| MK-4166 120 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.03 Days |
| MK-4166 170 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 4 | 0.02 Days |
| MK-4166 170 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.08 Days |
| MK-4166 170 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.08 Days |
| MK-4166 170 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.03 Days |
| MK-4166 240 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.04 Days |
| MK-4166 240 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.08 Days |
| MK-4166 240 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 4 | 0.05 Days |
| MK-4166 240 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.02 Days |
| MK-4166 340 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.03 Days |
| MK-4166 340 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 4 | 0.02 Days |
| MK-4166 340 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.02 Days |
| MK-4166 340 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.02 Days |
| MK-4166 480 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.05 Days |
| MK-4166 480 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.08 Days |
| MK-4166 480 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.08 Days |
| MK-4166 670 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.06 Days |
| MK-4166 670 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.02 Days |
| MK-4166 670 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 4 | 0.08 Days |
| MK-4166 670 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.05 Days |
| MK-4166 900 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 2 | 0.08 Days |
| MK-4166 900 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 4 | 0.08 Days |
| MK-4166 900 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 1 | 0.08 Days |
| MK-4166 900 mg + Pembro | Time to Maximum Concentration (Tmax) of MK-4166 Over Time | Cycle 3 | 0.03 Days |
Secondary
Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time
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.
Time frame: 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)
Population: All allocated participants who received ≥1 dose of pembrolizumab and had evaluable Tmax samples. Per protocol, MK-4166 monotherapy dose cohorts were not analyzed. Participants with samples that were hemolyzed or analyzed outside of stability were excluded from the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MK-4166 1.1 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 1 | 0.03 Days |
| MK-4166 1.1 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 3 | 0.03 Days |
| MK-4166 1.1 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 2 | 0.03 Days |
| MK-4166 1.1 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 4 | 0.13 Days |
| MK-4166 3.3 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 3 | 0.03 Days |
| MK-4166 3.3 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 2 | 0.03 Days |
| MK-4166 3.3 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 4 | 0.08 Days |
| MK-4166 3.3 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 1 | 0.06 Days |
| MK-4166 10 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 1 | 0.02 Days |
| MK-4166 10 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 4 | 0.04 Days |
| MK-4166 10 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 2 | 0.03 Days |
| MK-4166 10 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 3 | 0.03 Days |
| MK-4166 30 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 3 | 0.07 Days |
| MK-4166 30 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 1 | 0.08 Days |
| MK-4166 30 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 2 | 0.03 Days |
| MK-4166 30 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 4 | 0.04 Days |
| MK-4166 42 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 1 | 0.02 Days |
| MK-4166 42 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 4 | 0.04 Days |
| MK-4166 42 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 2 | 0.02 Days |
| MK-4166 42 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 3 | 0.02 Days |
| MK-4166 59 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 2 | 0.05 Days |
| MK-4166 59 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 1 | 0.03 Days |
| MK-4166 59 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 3 | 0.05 Days |
| MK-4166 59 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 4 | 0.07 Days |
| MK-4166 82 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 1 | 0.06 Days |
| MK-4166 82 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 3 | 0.03 Days |
| MK-4166 82 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 2 | 0.03 Days |
| MK-4166 120 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 2 | 0.13 Days |
| MK-4166 120 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 4 | 0.03 Days |
| MK-4166 120 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 3 | 0.05 Days |
| MK-4166 120 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 1 | 0.04 Days |
| MK-4166 170 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 3 | 0.05 Days |
| MK-4166 170 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 1 | 0.02 Days |
| MK-4166 170 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 2 | 0.05 Days |
| MK-4166 240 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 2 | 0.03 Days |
| MK-4166 240 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 4 | 7.07 Days |
| MK-4166 240 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 1 | 0.11 Days |
| MK-4166 240 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 3 | 0.93 Days |
| MK-4166 340 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 4 | 0.10 Days |
| MK-4166 340 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 1 | 0.07 Days |
| MK-4166 340 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 2 | 0.06 Days |
| MK-4166 340 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 3 | 0.02 Days |
| MK-4166 480 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 1 | 0.02 Days |
| MK-4166 480 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 2 | 0.07 Days |
| MK-4166 480 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 3 | 0.08 Days |
| MK-4166 670 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 2 | 0.02 Days |
| MK-4166 670 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 3 | 0.10 Days |
| MK-4166 670 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 4 | 0.02 Days |
| MK-4166 670 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 1 | 0.05 Days |
| MK-4166 900 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 4 | 0.03 Days |
| MK-4166 900 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 2 | 0.03 Days |
| MK-4166 900 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 1 | 0.02 Days |
| MK-4166 900 mg + Pembro | Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time | Cycle 3 | 0.05 Days |