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| ID | Type | Description | Link |
|---|---|---|---|
| MK-8628-006 | Other Identifier | Merck Protocol Number | |
| 2015-005488-18 | EudraCT Number |
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This study was terminated due to limited efficacy and not due to safety reasons.
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This is a study to determine the recommended dose of birabresib (MK-8628)(formerly known as OTX015) for further studies in participants with advanced nuclear protein in testis (NUT) midline carcinoma (NMC), triple negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), or castration-resistant prostate cancer (CRPC). This is a two-part parallel study: Part A will establish the recommended dose by evaluating dose limiting toxicity (DLT), safety, discontinuation, and early efficacy and Part B will enroll participants with NMC only and will evaluate safety and efficacy in this population.
The sponsor decided to terminate the program after evaluation of safety and efficacy data at the dose levels tested (Part A). The decision to discontinue the birabresib program was based on limited efficacy signals and was not due to safety-related concerns. No participants entered or were treated in Part B of the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Birabresib 20 mg CRPC Cohort-Part A | Experimental | Participants in the CRPC cohort in Part A of the study received birabresib 20 mg orally (PO), twice a day (BID), in a fasted state for 21 consecutive days per cycle. Participants received birabresib in continuous cycles up to 24 months. |
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| Birabresib 20 mg NMC Cohort-Part A | Experimental | Participants in the NMC cohort in Part A of the study received birabresib 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received birabresib in continuous cycles up to 24 months. |
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| Birabresib 20 mg TNBC Cohort-Part A | Experimental | Participants in the TNBC cohort in Part A of the study received birabresib 20 mg PO, BID, in a fasted state for 21 consecutive days per cycle. Participants received birabresib in continuous cycles up to 24 months. |
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| NMC Cohort-Part B | Experimental | Participants (up to 30) in Part B will receive birabresib at one dose level below the dose currently being administered in Part A of the study. Once the recommended Phase 2 dose (RP2D) from Part A is established, participants in Part B will receive birabresib at the RP2D. Participants will continue receiving birabresib at an assigned/adjusted dose level for continuous cycles up to 24 months. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Birabresib | Drug | Administered as an oral capsule in a fasted state |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | 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. | From time of first dose up to the end of the first cycle (up to 21 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Experienced at Least One Adverse Event (AE) | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | MK-8628 20 mg CRPC Cohort-Part A | 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. |
| FG001 | MK-8628 20 mg NMC Cohort-Part A |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 21, 2016 |
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| From time of first dose until the end of the 30-day follow-up (up to 25 months) |
| Number of Participants Who Discontinued Study Treatment Due to an AE | The number of participants who discontinued study treatment due to an AE is presented. | From time of first dose until the end of treatment (up to 24 months) |
| Objective Response Rate (ORR) | 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. | Assessed every 6 weeks from time of first dose until disease progression (up to 24 months) |
| Duration of Response (DOR) | 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. | Assessed every 6 weeks from time of first dose until disease progression (up to 24 months) |
| Disease Control Rate (DCR) | 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. | Assessed every 6 weeks from time of first dose until disease progression (up to 24 months) |
| Observed Maximum Concentration (Cmax) of MK-8628 | 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. | Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose |
| Observed Minimum Concentration (Cmin) of MK-8628 | 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. | Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose |
| Time to Maximum Concentration (Tmax) of MK-8628 | 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. | Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose |
| Apparent Terminal Half-Life (t1/2) of MK-8628 | 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. | Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose |
| Apparent Total Body Clearance (CL/F) of MK-8628 | 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. | Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose |
| Apparent Volume of Distribution During the Terminal Phase (Vz/F) of MK-8628 | 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. | Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose |
| Area Under the Concentration-time Curve of MK-8628 From Time 0 to Infinity (AUC 0-∞) | 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. | Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose |
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. |
| FG002 | MK-8628 20 mg TNBC Cohort-Part A | 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. |
| FG003 | NMC Cohort-Part B | 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. |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | MK-8628 20 mg CRPC Cohort-Part A | 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. |
| BG001 | MK-8628 20 mg NMC Cohort-Part A | 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. |
| BG002 | MK-8628 20 mg TNBC Cohort-Part A | 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. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Full Range | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | 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. | 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. | Posted | Count of Participants | Participants | From time of first dose up to the end of the first cycle (up to 21 days) |
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| Secondary | Number of Participants Who Experienced at Least One Adverse Event (AE) | 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. | 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. | Posted | Count of Participants | Participants | From time of first dose until the end of the 30-day follow-up (up to 25 months) |
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| Secondary | Number of Participants Who Discontinued Study Treatment Due to an AE | The number of participants who discontinued study treatment due to an AE is presented. | 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. | Posted | Count of Participants | Participants | From time of first dose until the end of treatment (up to 24 months) |
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| Secondary | Objective Response Rate (ORR) | 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. | 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. | Posted | Count of Participants | Participants | Assessed every 6 weeks from time of first dose until disease progression (up to 24 months) |
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| Secondary | Duration of Response (DOR) | 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. | 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. | Posted | Assessed every 6 weeks from time of first dose until disease progression (up to 24 months) |
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| Secondary | Disease Control Rate (DCR) | 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. | 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. | Posted | Count of Participants | Participants | Assessed every 6 weeks from time of first dose until disease progression (up to 24 months) |
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| Secondary | Observed Maximum Concentration (Cmax) of MK-8628 | 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. | 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. | Posted | Mean | Standard Deviation | ng/mL | Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose |
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| Secondary | Observed Minimum Concentration (Cmin) of MK-8628 | 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. | 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. | Posted | Mean | Standard Deviation | ng/mL | Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose |
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| Secondary | Time to Maximum Concentration (Tmax) of MK-8628 | 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. | 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. | Posted | Median | Full Range | hours | Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose |
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| Secondary | Apparent Terminal Half-Life (t1/2) of MK-8628 | 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. | 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. | Posted | Mean | Standard Deviation | hours | Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose |
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| Secondary | Apparent Total Body Clearance (CL/F) of MK-8628 | 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. | 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. | Posted | Mean | Standard Deviation | Liters/hour | Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose |
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| Secondary | Apparent Volume of Distribution During the Terminal Phase (Vz/F) of MK-8628 | 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. | 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. | Posted | Mean | Standard Deviation | Liters | Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose |
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| Secondary | Area Under the Concentration-time Curve of MK-8628 From Time 0 to Infinity (AUC 0-∞) | 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. | 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. | Posted | Mean | Standard Deviation | hours•ng/mL | Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose |
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From time of first dose until the end of the 30-day follow-up (up to 25 months)
The safety population consisted of all participants who received at least one dose of study treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | MK-8628 20 mg CRPC Cohort-Part A | 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. | 0 | 9 | 3 | 9 | 9 | 9 |
| EG001 | MK-8628 20 mg NMC Cohort-Part A | 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. | 0 | 3 | 2 | 3 | 3 | 3 |
| EG002 | MK-8628 20 mg TNBC Cohort-Part A | 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. | 0 | 1 | 0 | 1 | 1 | 1 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Neutrophil count decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
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| Altered state of consciousness | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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| Cognitive disorder | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
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| Leukocytosis | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
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| Leukopenia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | MedDRA 20.0 | Systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | MedDRA 20.0 | Systematic Assessment |
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| Vision blurred | Eye disorders | MedDRA 20.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Gastrointestinal pain | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Odynophagia | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Asthenia | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Mucosal inflammation | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 20.0 | Systematic Assessment |
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| Blood creatinine increased | Investigations | MedDRA 20.0 | Systematic Assessment |
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| C-reactive protein increased | Investigations | MedDRA 20.0 | Systematic Assessment |
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| Haemoglobin decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
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| Lymphocyte count decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
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| Platelet count decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
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| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
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| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
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| Scrotal oedema | Reproductive system and breast disorders | MedDRA 20.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Hot flush | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 20.0 | 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.
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| Apr 2, 2018 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D064726 | Triple Negative Breast Neoplasms |
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000605331 | OTX015 |
Not provided
Not provided
Not provided
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| OG002 | MK-8628 20 mg TNBC Cohort-Part A | 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. |
| OG003 | NMC Cohort-Part B | 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. |
|
|
| OG003 | NMC Cohort-Part B | 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. |
|
|
| OG002 | MK-8628 20 mg TNBC Cohort-Part A | 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. |
| OG003 | NMC Cohort-Part B | 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. |
|
|
| OG002 | MK-8628 20 mg TNBC Cohort-Part A | 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. |
| OG003 | NMC Cohort-Part B | 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. |
|
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. |
| OG002 | MK-8628 20 mg TNBC Cohort-Part A | 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. |
| OG003 | NMC Cohort-Part B | 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. |
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