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Study of MK-4166 and MK-4166 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4166-001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02132754
Recruitment Status : Completed
First Posted : May 7, 2014
Results First Posted : July 31, 2020
Last Update Posted : July 31, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.

Condition or disease Intervention/treatment Phase
Solid Tumor Biological: MK-4166 Biological: Pembrolizumab Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 116 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Trial of Single Agent MK-4166 and MK-4166 in Combination With Pembrolizumab in Subjects With Advanced Malignancies
Actual Study Start Date : June 27, 2014
Actual Primary Completion Date : July 31, 2019
Actual Study Completion Date : July 31, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Biological: MK-4166
Experimental: 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.
Biological: MK-4166
Experimental: 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.
Biological: MK-4166
Experimental: 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.
Biological: MK-4166
Experimental: 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.
Biological: MK-4166
Experimental: 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.
Biological: MK-4166
Experimental: 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.
Biological: MK-4166
Experimental: 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.
Biological: MK-4166
Experimental: MK-4166 10 mg
Participant received 10 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
Biological: MK-4166
Experimental: MK-4166 30 mg
Participants received 30 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
Biological: MK-4166
Experimental: MK-4166 42 mg
Participants received 42 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
Biological: MK-4166
Experimental: MK-4166 59 mg
Participants received 59 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
Biological: MK-4166
Experimental: MK-4166 82 mg
Participants received 82 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
Biological: MK-4166
Experimental: MK-4166 120 mg
Participants received 120 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
Biological: MK-4166
Experimental: MK-4166 170 mg
Participants received 170 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
Biological: MK-4166
Experimental: MK-4166 240 mg
Participants received 240 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
Biological: MK-4166
Experimental: MK-4166 340 mg
Participants received 340 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
Biological: MK-4166
Experimental: MK-4166 480 mg
Participants received 480 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
Biological: MK-4166
Experimental: MK-4166 670 mg
Participants received 670 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
Biological: MK-4166
Experimental: MK-4166 900 mg
Participants received 900 mg MK-4166 IV on Day 1 of each 21-day cycle for up to 4 cycles.
Biological: MK-4166
Experimental: 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.
Biological: MK-4166
Biological: Pembrolizumab
Experimental: 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.
Biological: MK-4166
Biological: Pembrolizumab
Experimental: 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.
Biological: MK-4166
Biological: Pembrolizumab
Experimental: 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.
Biological: MK-4166
Biological: Pembrolizumab
Experimental: 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.
Biological: MK-4166
Biological: Pembrolizumab
Experimental: 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.
Biological: MK-4166
Biological: Pembrolizumab
Experimental: 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.
Biological: MK-4166
Biological: Pembrolizumab
Experimental: 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.
Biological: MK-4166
Biological: Pembrolizumab
Experimental: 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.
Biological: MK-4166
Biological: Pembrolizumab
Experimental: 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.
Biological: MK-4166
Biological: Pembrolizumab
Experimental: 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.
Biological: MK-4166
Biological: Pembrolizumab
Experimental: 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.
Biological: MK-4166
Biological: Pembrolizumab
Experimental: 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.
Biological: MK-4166
Biological: Pembrolizumab
Experimental: 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.
Biological: MK-4166
Biological: Pembrolizumab



Primary Outcome Measures :
  1. Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) [ Time Frame: 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.

  2. Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: 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.


  3. Number of Participants Discontinuing Study Treatment Due to AEs [ Time Frame: 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 Outcome Measures :
  1. Maximum Concentration (Cmax) of MK-4166 Over Time [ 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) ]
    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.

  2. Time to Maximum Concentration (Tmax) of MK-4166 Over Time [ 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) ]
    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.

  3. Terminal Half-Life (t ½) of MK-4166 Over Time [ 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) ]
    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.

  4. Area Under the Concentration-Time Curve of MK-4166 From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time [ 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) ]
    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.

  5. Area Under the Concentration-Time Curve of MK-4166 From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time [ 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) ]
    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.

  6. Area Under the Concentration-Time Curve of MK-4166 From Time Zero to Infinity (AUC 0-inf) Over Time [ 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) ]
    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.

  7. Apparent Clearance (CL) of MK-4166 Over Time [ 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) ]
    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.

  8. Apparent Volume of Distribution (V) of MK-4166 Over Time [ 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) ]
    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.

  9. Maximum Concentration (Cmax) of Pembrolizumab Over Time [ 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) ]
    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.

  10. Time to Maximum Concentration (Tmax) of Pembrolizumab Over Time [ 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) ]
    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.

  11. Terminal Half-Life (t ½) of Pembrolizumab Over Time [ 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) ]
    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.

  12. Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to 21 Hours After Dosing (AUC 0-21) Over Time [ 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) ]
    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.

  13. Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to The Last Quantifiable Sample (AUC 0-last) Over Time [ 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) ]
    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.

  14. Area Under the Concentration-Time Curve of Pembrolizumab From Time Zero to Infinity (AUC 0-inf) Over Time [ 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) ]
    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.

  15. Apparent Clearance (CL) of Pembrolizumab Over Time [ 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) ]
    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.

  16. Apparent Volume of Distribution (V) of Pembrolizumab Over Time [ 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) ]
    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.

  17. Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein (GITR) Receptor Availability Following MK-4166 Administration [ 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. ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02132754


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme Corp.
  Study Documents (Full-Text)

Documents provided by Merck Sharp & Dohme Corp.:
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02132754    
Other Study ID Numbers: 4166-001
MK-4166-001 ( Other Identifier: Merck )
First Posted: May 7, 2014    Key Record Dates
Results First Posted: July 31, 2020
Last Update Posted: July 31, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Additional relevant MeSH terms:
Layout table for MeSH terms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents