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A Dose Exploration Study With MK-8628 in Participants With Selected Advanced Solid Tumors (MK-8628-006)

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ClinicalTrials.gov Identifier: NCT02698176
Recruitment Status : Terminated (This study was terminated due to limited efficacy and not due to safety reasons.)
First Posted : March 3, 2016
Results First Posted : November 5, 2018
Last Update Posted : November 5, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions NUT Midline Carcinoma (NMC)
Triple Negative Breast Cancer (TNBC)
Non-small Cell Lung Cancer (NSCLC)
Castration-resistant Prostate Cancer (CRPC)
Intervention Drug: MK-8628
Enrollment 13
Recruitment Details This was a dose-escalating study in participants with advanced or metastatic non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), castration-resistant prostate cancer (CRPC), or nuclear protein in testis (NUT) midline carcinoma (NMC) for which standard therapy does not exist, proven ineffective, intolerable, or unacceptable.
Pre-assignment Details Participants with CRPC, NMC, and TNBC, as defined in the entry criteria, were enrolled; no participants with NSCLC were enrolled. All participants had a Eastern Cooperative Oncology Group (ECOG) Performance Status score of ≤1 and 76.9% of participants had 2 or more prior lines of therapy. No participants were enrolled in Part B of the study.
Arm/Group Title MK-8628 20 mg CRPC Cohort-Part A MK-8628 20 mg NMC Cohort-Part A MK-8628 20 mg TNBC Cohort-Part A NMC Cohort-Part B
Hide Arm/Group Description Participants in the CRPC cohort in Part A of the study received MK-8628 20 mg orally (PO), twice a day (BID), in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months. Participants in the NMC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months. Participants in the TNBC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months. Participants (up to 30) in Part B were to receive MK-8628 at one dose level below the dose that was currently being administered in the escalation portion of Part A of the study. Once the recommended Phase 2 dose (RP2D) from Part A was established, participants in Part B were to receive MK-8628 at the RP2D. Participants were to continue receiving MK-8628 at an assigned/adjusted dose level for continuous cycles up to 24 months.
Period Title: Overall Study
Started 9 3 1 0 [1]
Completed 0 0 0 0
Not Completed 9 3 1 0
Reason Not Completed
Progressive disease             4             3             1             0
Adverse Event             2             0             0             0
Clinical progression             3             0             0             0
[1]
No participants were enrolled in Part B.
Arm/Group Title MK-8628 20 mg CRPC Cohort-Part A MK-8628 20 mg NMC Cohort-Part A MK-8628 20 mg TNBC Cohort-Part A Total
Hide Arm/Group Description Participants in the CRPC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months. Participants in the NMC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months. Participants in the TNBC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months. Total of all reporting groups
Overall Number of Baseline Participants 9 3 1 13
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 9 participants 3 participants 1 participants 13 participants
71.2
(67 to 81)
42.7
(30 to 67)
66.0
(66 to 66)
64.2
(30 to 81)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 3 participants 1 participants 13 participants
Female
0
   0.0%
1
  33.3%
1
 100.0%
2
  15.4%
Male
9
 100.0%
2
  66.7%
0
   0.0%
11
  84.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 3 participants 1 participants 13 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
  11.1%
0
   0.0%
0
   0.0%
1
   7.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
8
  88.9%
3
 100.0%
1
 100.0%
12
  92.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1
Hide Description A DLT was any of the following deemed drug related (DR) by investigator: Grade (G)4 hematologic toxicity lasting ≥7 days except thrombocytopenia; G4 thrombocytopenia; G3 thrombocytopenia with bleeding; G3 or 4 febrile neutropenia. G4 non-hematologic (NH) toxicity (not laboratory); G3 NH toxicity (not laboratory), nausea, vomiting, or diarrhea lasting >3 days despite supportive care; G3 or 4 NH laboratory abnormality requiring medical intervention, hospitalization, or persisting >1 week; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >8X Upper Limit of Normal(ULN); ALT or AST >5XULN for >2 weeks; ALT or AST >3XULN and total bilirubin >2XULN or international normalization ratio >1.5; ALT or AST >3XULN with fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash and/or eosinophilia (>5%); DR adverse event leading to discontinuation or >20% missed planned doses in Cycle 1; DR toxicity causing >2 week delay in starting Cycle 2; or G5 toxicity.
Time Frame From time of first dose up to the end of the first cycle (up to 21 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Part A of the study that received at least 85% of the planned MK-8628 20 mg dose (18 days) or experienced a DLT during the first 21-day cycle.
Arm/Group Title MK-8628 20 mg CRPC Cohort-Part A MK-8628 20 mg NMC Cohort-Part A MK-8628 20 mg TNBC Cohort-Part A
Hide Arm/Group Description:
Participants in the CRPC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months.
Participants in the NMC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months.
Participants in the TNBC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months.
Overall Number of Participants Analyzed 9 3 1
Measure Type: Count of Participants
Unit of Measure: Participants
2
  22.2%
1
  33.3%
0
   0.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MK-8628 20 mg CRPC Cohort-Part A, MK-8628 20 mg NMC Cohort-Part A, MK-8628 20 mg TNBC Cohort-Part A
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimation of DLT Rate
Estimated Value 0.25
Confidence Interval (2-Sided) 80%
0.121 to 0.418
Estimation Comments Point estimate and 2-sided 80% Bayesian credible interval for DLT rate estimated for the total number of participants from all 3 cohorts (CRPC+NMC+TNBC) that were evaluable for DLT analysis based on a non-informative prior distribution of Beta (1,1).
2.Secondary Outcome
Title Number of Participants Who Experienced at Least One Adverse Event (AE)
Hide Description An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. The number of participants who experienced at least one AE is presented.
Time Frame From time of first dose until the end of the 30-day follow-up (up to 25 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Part A of the study that received at least 1 dose of MK-8628 20 mg. No participants were enrolled in Part B of the study.
Arm/Group Title MK-8628 20 mg CRPC Cohort-Part A MK-8628 20 mg NMC Cohort-Part A MK-8628 20 mg TNBC Cohort-Part A NMC Cohort-Part B
Hide Arm/Group Description:
Participants in the CRPC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months.
Participants in the NMC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months.
Participants in the TNBC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months.
Participants (up to 30) in Part B were to receive MK-8628 at one dose level below the dose that was currently being administered in the escalation portion of Part A of the study. Once the recommended Phase 2 dose (RP2D) from Part A was established, participants in Part B were to receive MK-8628 at the RP2D. Participants were to continue receiving MK-8628 at an assigned/adjusted dose level for continuous cycles up to 24 months.
Overall Number of Participants Analyzed 9 3 1 0
Measure Type: Count of Participants
Unit of Measure: Participants
9
 100.0%
3
 100.0%
1
 100.0%
3.Secondary Outcome
Title Number of Participants Who Discontinued Study Treatment Due to an AE
Hide Description The number of participants who discontinued study treatment due to an AE is presented.
Time Frame From time of first dose until the end of treatment (up to 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Part A of the study that received at least 1 dose of MK-8628 20 mg. No participants were enrolled in Part B of the study.
Arm/Group Title MK-8628 20 mg CRPC Cohort-Part A MK-8628 20 mg NMC Cohort-Part A MK-8628 20 mg TNBC Cohort-Part A NMC Cohort-Part B
Hide Arm/Group Description:
Participants in the CRPC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months.
Participants in the NMC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months.
Participants in the TNBC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months.
Participants (up to 30) in Part B were to receive MK-8628 at one dose level below the dose that was currently being administered in the escalation portion of Part A of the study. Once the recommended Phase 2 dose (RP2D) from Part A was established, participants in Part B were to receive MK-8628 at the RP2D. Participants were to continue receiving MK-8628 at an assigned/adjusted dose level for continuous cycles up to 24 months.
Overall Number of Participants Analyzed 9 3 1 0
Measure Type: Count of Participants
Unit of Measure: Participants
2
  22.2%
0
   0.0%
0
   0.0%
4.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description ORR was defined as the percentage of the participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions per RECIST 1.1) and lack of progression according to the guidelines for prostate cancer endpoints developed by Prostate Cancer Clinical Trials Working Group (PCWG) 2 as assessed by investigator radiologic review. The number of participants who achieved a CR or PR is presented.
Time Frame Assessed every 6 weeks from time of first dose until disease progression (up to 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Part A of the study who received at least one dose of MK-8628 20 mg. No participants were enrolled in Part B of the study.
Arm/Group Title MK-8628 20 mg CRPC Cohort-Part A MK-8628 20 mg NMC Cohort-Part A MK-8628 20 mg TNBC Cohort-Part A NMC Cohort-Part B
Hide Arm/Group Description:
Participants in the CRPC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months.
Participants in the NMC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months.
Participants in the TNBC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months.
Participants (up to 30) in Part B were to receive MK-8628 at one dose level below the dose that was currently being administered in the escalation portion of Part A of the study. Once the recommended Phase 2 dose (RP2D) from Part A was established, participants in Part B were to receive MK-8628 at the RP2D. Participants were to continue receiving MK-8628 at an assigned/adjusted dose level for continuous cycles up to 24 months.
Overall Number of Participants Analyzed 9 3 1 0
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
5.Secondary Outcome
Title Duration of Response (DOR)
Hide Description For participants who demonstrated CR or PR, DOR was defined as the time from first documented evidence of CR or PR per RECIST 1.1 until disease progression per RECIST 1.1 and PCWG2 or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression per RECIST 1.1. Per PCWG2, progressive disease was defined as a confirmed increase of at least two new lesions on a bone scan. DOR assessments were assessed by investigator radiologic review. The DOR for all participants who experienced a CR or PR is presented.
Time Frame Assessed every 6 weeks from time of first dose until disease progression (up to 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Part A of the study who received at least one dose of MK-8628 20 mg. No participants were enrolled in Part B of the study. Since no participants experienced a CR or PR, DOR could not be calculated.
Arm/Group Title MK-8628 20 mg CRPC Cohort-Part A MK-8628 20 mg NMC Cohort-Part A MK-8628 20 mg TNBC Cohort-Part A NMC Cohort-Part B
Hide Arm/Group Description:
Participants in the CRPC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months.
Participants in the NMC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months.
Participants in the TNBC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months.
Participants (up to 30) in Part B were to receive MK-8628 at one dose level below the dose that was currently being administered in the escalation portion of Part A of the study. Once the recommended Phase 2 dose (RP2D) from Part A was established, participants in Part B were to receive MK-8628 at the RP2D. Participants were to continue receiving MK-8628 at an assigned/adjusted dose level for continuous cycles up to 24 months.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description DCR was defined as the number of subjects with CR, PR, or stable disease (SD) as assessed by investigator radiologic review according to RECIST version 1.1 and PCWG2. CR: defined as disappearance of all target and all non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than <10 mm per RECIST 1.1. PR: defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters along with absence of new lesions and disease progression in non-target lesions per RECIST 1.1. SD: defined as, neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study per RECIST 1.1 and lack of a confirmed increase of at least two new lesions on a bone scan per PCWG2. The number of participants who experienced DCR is presented.
Time Frame Assessed every 6 weeks from time of first dose until disease progression (up to 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Part A of the study who received at least one dose of MK-8628 20 mg. No participants were enrolled in Part B of the study.
Arm/Group Title MK-8628 20 mg CRPC Cohort-Part A MK-8628 20 mg NMC Cohort-Part A MK-8628 20 mg TNBC Cohort-Part A NMC Cohort-Part B
Hide Arm/Group Description:
Participants in the CRPC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months.
Participants in the NMC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months.
Participants in the TNBC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months.
Participants (up to 30) in Part B were to receive MK-8628 at one dose level below the dose that was currently being administered in the escalation portion of Part A of the study. Once the recommended Phase 2 dose (RP2D) from Part A was established, participants in Part B were to receive MK-8628 at the RP2D. Participants were to continue receiving MK-8628 at an assigned/adjusted dose level for continuous cycles up to 24 months.
Overall Number of Participants Analyzed 9 3 1 0
Measure Type: Count of Participants
Unit of Measure: Participants
6
  66.7%
0
   0.0%
0
   0.0%
7.Secondary Outcome
Title Observed Maximum Concentration (Cmax) of MK-8628
Hide Description Blood samples were obtained at specified time points for the pharmacokinetic (PK) analysis of Cmax of MK-8628. MK-8628 concentrations were analyzed using ultra-performance liquid chromatography coupled with a tandem mass spectrometry. The Cmax of MK-8628 after oral administration is presented.
Time Frame Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Total number of participants from all 3 cohorts (CRPC+NMC+TNBC) in Part A of the study that received at least 1 dose of MK-8628 20 mg and had data available for the PK parameter being analyzed.
Arm/Group Title MK-8628 20 mg PK Cohort
Hide Arm/Group Description:
Total number of participants from all 3 cohorts (CRPC+NMC+TNBC) in Part A of the study that received at least 1 dose of MK-8628 20 mg PO, BID, in a fasted state.
Overall Number of Participants Analyzed 13
Mean (Standard Deviation)
Unit of Measure: ng/mL
355  (157)
8.Secondary Outcome
Title Observed Minimum Concentration (Cmin) of MK-8628
Hide Description Blood samples were obtained at specified time points for the PK analysis of Cmin of MK-8628. MK-8628 concentrations were analyzed using ultra-performance liquid chromatography coupled with a tandem mass spectrometry. The Cmin of MK-8628 after oral administration is presented.
Time Frame Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Total number of participants from all 3 cohorts (CRPC+NMC+TNBC) in Part A of the study that received at least 1 dose of MK-8628 20 mg and had data available for the PK parameter being analyzed.
Arm/Group Title MK-8628 20 mg PK Cohort
Hide Arm/Group Description:
Total number of participants from all 3 cohorts (CRPC+NMC+TNBC) in Part A of the study that received at least 1 dose of MK-8628 20 mg PO, BID, in a fasted state.
Overall Number of Participants Analyzed 13
Mean (Standard Deviation)
Unit of Measure: ng/mL
111  (45.9)
9.Secondary Outcome
Title Time to Maximum Concentration (Tmax) of MK-8628
Hide Description Blood samples were obtained at specified time points for the PK analysis of Tmax of MK-8628. MK-8628 concentrations were analyzed using ultra-performance liquid chromatography coupled with a tandem mass spectrometry. The Tmax of MK-8628 after oral administration is presented.
Time Frame Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Total number of participants from all 3 cohorts (CRPC+NMC+TNBC) in Part A of the study that received at least 1 dose of MK-8628 20 mg and had data available for the PK parameter being analyzed.
Arm/Group Title MK-8628 20 mg PK Cohort
Hide Arm/Group Description:
Total number of participants from all 3 cohorts (CRPC+NMC+TNBC) in Part A of the study that received at least 1 dose of MK-8628 20 mg PO, BID, in a fasted state.
Overall Number of Participants Analyzed 13
Median (Full Range)
Unit of Measure: hours
2.25
(1.00 to 3.25)
10.Secondary Outcome
Title Apparent Terminal Half-Life (t1/2) of MK-8628
Hide Description Blood samples were obtained at specified time points for the PK analysis of t1/2 of MK-8628. MK-8628 concentrations were analyzed using ultra-performance liquid chromatography coupled with a tandem mass spectrometry. The t1/2 of MK-8628 after oral administration is presented.
Time Frame Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Total number of participants from all 3 cohorts (CRPC+NMC+TNBC) in Part A of the study that received at least 1 dose of MK-8628 20 mg and had data available for the PK parameter being analyzed.
Arm/Group Title MK-8628 20 mg PK Cohort
Hide Arm/Group Description:
Total number of participants from all 3 cohorts (CRPC+NMC+TNBC) in Part A of the study that received at least 1 dose of MK-8628 20 mg PO, BID, in a fasted state.
Overall Number of Participants Analyzed 13
Mean (Standard Deviation)
Unit of Measure: hours
6.17  (1.17)
11.Secondary Outcome
Title Apparent Total Body Clearance (CL/F) of MK-8628
Hide Description Blood samples were obtained at specified time points for the PK analysis of Cl/F of MK-8628. MK-8628 concentrations were analyzed using ultra-performance liquid chromatography coupled with a tandem mass spectrometry. The Cl/F of MK-8628 after oral administration is presented.
Time Frame Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Total number of participants from all 3 cohorts (CRPC+NMC+TNBC) in Part A of the study that received at least 1 dose of MK-8628 20 mg and had data available for the PK parameter being analyzed.
Arm/Group Title MK-8628 20 mg PK Cohort
Hide Arm/Group Description:
Total number of participants from all 3 cohorts (CRPC+NMC+TNBC) in Part A of the study that received at least 1 dose of MK-8628 20 mg PO, BID, in a fasted state.
Overall Number of Participants Analyzed 13
Mean (Standard Deviation)
Unit of Measure: Liters/hour
6.44  (2.23)
12.Secondary Outcome
Title Apparent Volume of Distribution During the Terminal Phase (Vz/F) of MK-8628
Hide Description Blood samples were obtained at specified time points for the PK analysis of Vz/F of MK-8628. MK-8628 concentrations were analyzed using ultra-performance liquid chromatography coupled with a tandem mass spectrometry. The Vz/F of MK-8628 after oral administration is presented.
Time Frame Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Total number of participants from all 3 cohorts (CRPC+NMC+TNBC) in Part A of the study that received at least 1 dose of MK-8628 20 mg and had data available for the PK parameter being analyzed.
Arm/Group Title MK-8628 20 mg PK Cohort
Hide Arm/Group Description:
Total number of participants from all 3 cohorts (CRPC+NMC+TNBC) in Part A of the study that received at least 1 dose of MK-8628 20 mg PO, BID, in a fasted state.
Overall Number of Participants Analyzed 13
Mean (Standard Deviation)
Unit of Measure: Liters
55.0  (15.3)
13.Secondary Outcome
Title Area Under the Concentration-time Curve of MK-8628 From Time 0 to Infinity (AUC 0-∞)
Hide Description Blood samples were obtained at specified time points for the PK analysis of AUC 0-∞ of MK-8628. MK-8628 concentrations were analyzed using ultra-performance liquid chromatography coupled with a tandem mass spectrometry. The AUC 0-∞ of MK-8628 after oral administration is presented.
Time Frame Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Total number of participants from all 3 cohorts (CRPC+NMC+TNBC) in Part A of the study that received at least 1 dose of MK-8628 20 mg and had data available for the PK parameter being analyzed.
Arm/Group Title MK-8628 20 mg DLT Cohort
Hide Arm/Group Description:
Total number of participants from all 3 cohorts (CRPC+NMC+TNBC) in Part A of the study that received at least 1 dose of MK-8628 20 mg PO, BID, in a fasted state.
Overall Number of Participants Analyzed 13
Mean (Standard Deviation)
Unit of Measure: hours•ng/mL
3520  (1410)
Time Frame From time of first dose until the end of the 30-day follow-up (up to 25 months)
Adverse Event Reporting Description The safety population consisted of all participants who received at least one dose of study treatment.
 
Arm/Group Title MK-8628 20 mg CRPC Cohort-Part A MK-8628 20 mg NMC Cohort-Part A MK-8628 20 mg TNBC Cohort-Part A
Hide Arm/Group Description Participants in the CRPC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months. Participants in the NMC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months. Participants in the TNBC cohort in Part A of the study received MK-8628 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received MK-8628 in continuous cycles up to 24 months.
All-Cause Mortality
MK-8628 20 mg CRPC Cohort-Part A MK-8628 20 mg NMC Cohort-Part A MK-8628 20 mg TNBC Cohort-Part A
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/9 (0.00%)      0/3 (0.00%)      0/1 (0.00%)    
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MK-8628 20 mg CRPC Cohort-Part A MK-8628 20 mg NMC Cohort-Part A MK-8628 20 mg TNBC Cohort-Part A
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/9 (33.33%)      2/3 (66.67%)      0/1 (0.00%)    
Blood and lymphatic system disorders       
Thrombocytopenia  1  0/9 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
Gastrointestinal disorders       
Diarrhoea  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
General disorders       
Pyrexia  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Investigations       
Neutrophil count decreased  1  0/9 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
Nervous system disorders       
Altered state of consciousness  1  0/9 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
Cognitive disorder  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Renal and urinary disorders       
Haematuria  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
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Frequency Threshold for Reporting Other Adverse Events 5%
MK-8628 20 mg CRPC Cohort-Part A MK-8628 20 mg NMC Cohort-Part A MK-8628 20 mg TNBC Cohort-Part A
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/9 (100.00%)      3/3 (100.00%)      1/1 (100.00%)    
Blood and lymphatic system disorders       
Anaemia  1  2/9 (22.22%)  2 0/3 (0.00%)  0 0/1 (0.00%)  0
Leukocytosis  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Leukopenia  1  0/9 (0.00%)  0 0/3 (0.00%)  0 1/1 (100.00%)  1
Thrombocytopenia  1  2/9 (22.22%)  2 0/3 (0.00%)  0 0/1 (0.00%)  0
Cardiac disorders       
Atrial fibrillation  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Ear and labyrinth disorders       
Vertigo  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Eye disorders       
Vision blurred  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Gastrointestinal disorders       
Abdominal pain  1  3/9 (33.33%)  4 0/3 (0.00%)  0 0/1 (0.00%)  0
Abdominal pain upper  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Constipation  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Diarrhoea  1  3/9 (33.33%)  7 1/3 (33.33%)  1 0/1 (0.00%)  0
Dyspepsia  1  2/9 (22.22%)  2 0/3 (0.00%)  0 0/1 (0.00%)  0
Dysphagia  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Gastrointestinal pain  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Nausea  1  6/9 (66.67%)  7 1/3 (33.33%)  1 0/1 (0.00%)  0
Odynophagia  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Vomiting  1  3/9 (33.33%)  4 1/3 (33.33%)  1 0/1 (0.00%)  0
General disorders       
Asthenia  1  2/9 (22.22%)  2 1/3 (33.33%)  1 0/1 (0.00%)  0
Fatigue  1  2/9 (22.22%)  4 2/3 (66.67%)  2 0/1 (0.00%)  0
Mucosal inflammation  1  0/9 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
Oedema peripheral  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Pyrexia  1  2/9 (22.22%)  2 0/3 (0.00%)  0 0/1 (0.00%)  0
Infections and infestations       
Respiratory tract infection  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Rhinitis  1  0/9 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
Sepsis  1  0/9 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
Injury, poisoning and procedural complications       
Fall  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Investigations       
Alanine aminotransferase increased  1  1/9 (11.11%)  3 0/3 (0.00%)  0 0/1 (0.00%)  0
Aspartate aminotransferase increased  1  1/9 (11.11%)  3 0/3 (0.00%)  0 0/1 (0.00%)  0
Blood creatinine increased  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
C-reactive protein increased  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Haemoglobin decreased  1  1/9 (11.11%)  2 0/3 (0.00%)  0 0/1 (0.00%)  0
Lymphocyte count decreased  1  0/9 (0.00%)  0 0/3 (0.00%)  0 1/1 (100.00%)  1
Platelet count decreased  1  2/9 (22.22%)  2 0/3 (0.00%)  0 1/1 (100.00%)  1
Weight decreased  1  0/9 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
Metabolism and nutrition disorders       
Decreased appetite  1  2/9 (22.22%)  2 2/3 (66.67%)  2 0/1 (0.00%)  0
Dehydration  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Hyperuricaemia  1  0/9 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
Hypokalaemia  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Hyponatraemia  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Hypophosphataemia  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Bone pain  1  2/9 (22.22%)  2 0/3 (0.00%)  0 0/1 (0.00%)  0
Musculoskeletal pain  1  1/9 (11.11%)  1 2/3 (66.67%)  2 0/1 (0.00%)  0
Myalgia  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Nervous system disorders       
Dysgeusia  1  0/9 (0.00%)  0 2/3 (66.67%)  2 0/1 (0.00%)  0
Headache  1  0/9 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
Renal and urinary disorders       
Haematuria  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Reproductive system and breast disorders       
Scrotal oedema  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Cough  1  1/9 (11.11%)  1 1/3 (33.33%)  1 0/1 (0.00%)  0
Dyspnoea  1  0/9 (0.00%)  0 2/3 (66.67%)  2 0/1 (0.00%)  0
Dyspnoea exertional  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Oropharyngeal pain  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Skin and subcutaneous tissue disorders       
Dry skin  1  0/9 (0.00%)  0 2/3 (66.67%)  2 0/1 (0.00%)  0
Erythema  1  0/9 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
Rash  1  0/9 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
Rash maculo-papular  1  1/9 (11.11%)  1 0/3 (0.00%)  0 0/1 (0.00%)  0
Vascular disorders       
Hot flush  1  0/9 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
Hypertension  1  0/9 (0.00%)  0 1/3 (33.33%)  1 0/1 (0.00%)  0
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
The study was terminated due to limited efficacy and not due to safety reasons. Due to limited PK sampling for t1/2, caution must be exercised when interpreting the results of t1/2, CL/F, and AUC 0-∞ values.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Results Point of Contact
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02698176     History of Changes
Other Study ID Numbers: 8628-006
MK-8628-006 ( Other Identifier: Merck Protocol Number )
2015-005488-18 ( EudraCT Number )
First Submitted: February 29, 2016
First Posted: March 3, 2016
Results First Submitted: April 2, 2018
Results First Posted: November 5, 2018
Last Update Posted: November 5, 2018