Castration-resistant Prostate Cancer (CRPC), Non-small Cell Lung Cancer (NSCLC), NUT Midline Carcinoma (NMC), Triple Negative Breast Cancer (TNBC)
Conditions
Keywords
OTX015, MK-8628
Brief summary
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.
Detailed description
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.
Interventions
DRUGBirabresib
Administered as an oral capsule in a fasted state
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males and females ≥18 years of age for NSCLC, TNBC, and CRPC * Males and females ≥16 years of age for NMC * Diagnosis of one of the following advanced solid tumors for which standard therapy either does not exist or has proven ineffective, intolerable or inacceptable for the participant: NMC;TNBC; NSCLC; or CRPC * Have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. CRPC participants may be enrolled with objective evidence of disease as per Prostate Cancer Working Group (PCWG2) criteria * Life expectancy ≥3 months * Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1 * Have an interval of ≥3 weeks (or ≥2 weeks for NMC participants) since chemotherapy (≥6 weeks for nitrosoureas or mitomycin C), immunotherapy, hormone therapy or any other anticancer therapy or surgical intervention resection, or ≥3 half-lives for monoclonal antibodies, or ≥5 half-lives for other non-cytotoxic agents (whichever is longer) * CRPC participants must maintain ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue, antagonist or orchiectomy providing serum testosterone is \<50 ng/dL (\<1.7 nmol/L) * Participants receiving bisphosphonate or denosumab therapy must be on stable doses for at least 4 weeks before start of study therapy * Females must not be pregnant (negative urine or serum human chorionic gonadotropin test within 72 hours of study start) * Females of childbearing potential and male participants must agree to use adequate contraception starting with the first dose of trial treatment through 90 days after the last dose of study medication
Exclusion criteria
* Has inability to swallow oral medications or presence of a gastrointestinal disorder (e.g. malabsorption) deemed to jeopardize intestinal absorption of birabresib * Has persistent grade \>1 clinically significant toxicities related to prior antineoplastic therapies (except for alopecia). Stable sensory neuropathy ≤ grade 2 National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 is accepted * Known primary central nervous system (CNS) malignancy or symptomatic or untreated CNS metastases. Treated and stable CNS metastases are allowed. * History of prior or concomitant malignancies within 3 years of study start * Have other serious illness or medical condition, such as active infection, unresolved bowel obstruction, psychiatric disorders, or cerebrovascular accident within 1 year of study start * Known human immunodeficiency virus (HIV) and/or active Hepatitis B or C infections * Have one of the following cardiac-related conditions: Congestive heart failure or angina pectoris (except if medically controlled); myocardial infarction (within 1 year of study start); uncontrolled hypertension; or uncontrolled arrhythmias * Other concomitant anticancer treatment * Participation in another clinical trial or treatment with any investigational drug (excluding anticancer treatments) within 30 days of study start * Concomitant therapy with strong CYP3A4 inhibitors or inducers * Therapeutic anticoagulation (e.g. warfarin, heparin, etc.) must be stopped at least 7 days prior to the first dose of birabresib. Low-dose low molecular weight heparin (LMWH) is permitted * Is pregnant or breast-feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | From time of first dose up to the end of the first cycle (up to 21 days) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Maximum Concentration (Tmax) of MK-8628 | Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose | 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. |
| Number of Participants Who Experienced at Least One Adverse Event (AE) | From time of first dose until the end of the 30-day follow-up (up to 25 months) | 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. |
| Number of Participants Who Discontinued Study Treatment Due to an AE | From time of first dose until the end of treatment (up to 24 months) | The number of participants who discontinued study treatment due to an AE is presented. |
| Objective Response Rate (ORR) | Assessed every 6 weeks from time of first dose until disease progression (up to 24 months) | 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. |
| Duration of Response (DOR) | Assessed every 6 weeks from time of first dose until disease progression (up to 24 months) | 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. |
| Disease Control Rate (DCR) | Assessed every 6 weeks from time of first dose until disease progression (up to 24 months) | 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. |
| Observed Maximum Concentration (Cmax) of MK-8628 | Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose | 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. |
| Observed Minimum Concentration (Cmin) of MK-8628 | Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose | 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. |
| Apparent Terminal Half-Life (t1/2) of MK-8628 | Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose | 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. |
| Apparent Total Body Clearance (CL/F) of MK-8628 | Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose | 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. |
| Apparent Volume of Distribution During the Terminal Phase (Vz/F) of MK-8628 | Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose | 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. |
| Area Under the Concentration-time Curve of MK-8628 From Time 0 to Infinity (AUC 0-∞) | Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose | 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. |
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 9 |
| 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. | 3 |
| 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. | 1 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 0 | 0 |
| Overall Study | Clinical progression | 3 | 0 | 0 | 0 |
| Overall Study | Progressive disease | 4 | 3 | 1 | 0 |
Baseline characteristics
| Characteristic | 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 |
|---|---|---|---|---|
| Age, Continuous | 71.2 Years | 42.7 Years | 66.0 Years | 64.2 Years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 3 Participants | 1 Participants | 12 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 9 Participants | 2 Participants | 0 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 3 | 0 / 1 |
| other Total, other adverse events | 9 / 9 | 3 / 3 | 1 / 1 |
| serious Total, serious adverse events | 3 / 9 | 2 / 3 | 0 / 1 |
Outcome results
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.
Time frame: From time of first dose up to the end of the first cycle (up to 21 days)
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-8628 20 mg CRPC Cohort-Part A | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | 2 Participants |
| MK-8628 20 mg NMC Cohort-Part A | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | 1 Participants |
| MK-8628 20 mg TNBC Cohort-Part A | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 | 0 Participants |
80% CI: [0.121, 0.418]
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.
Time frame: Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-8628 20 mg CRPC Cohort-Part A | Apparent Terminal Half-Life (t1/2) of MK-8628 | 6.17 hours | Standard Deviation 1.17 |
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.
Time frame: Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-8628 20 mg CRPC Cohort-Part A | Apparent Total Body Clearance (CL/F) of MK-8628 | 6.44 Liters/hour | Standard Deviation 2.23 |
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.
Time frame: Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-8628 20 mg CRPC Cohort-Part A | Apparent Volume of Distribution During the Terminal Phase (Vz/F) of MK-8628 | 55.0 Liters | Standard Deviation 15.3 |
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.
Time frame: Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-8628 20 mg CRPC Cohort-Part A | Area Under the Concentration-time Curve of MK-8628 From Time 0 to Infinity (AUC 0-∞) | 3520 hours•ng/mL | Standard Deviation 1410 |
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.
Time frame: Assessed every 6 weeks from time of first dose until disease progression (up to 24 months)
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-8628 20 mg CRPC Cohort-Part A | Disease Control Rate (DCR) | 6 Participants |
| MK-8628 20 mg NMC Cohort-Part A | Disease Control Rate (DCR) | 0 Participants |
| MK-8628 20 mg TNBC Cohort-Part A | Disease Control Rate (DCR) | 0 Participants |
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.
Time frame: Assessed every 6 weeks from time of first dose until disease progression (up to 24 months)
Population: 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.
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.
Time frame: From time of first dose until the end of treatment (up to 24 months)
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-8628 20 mg CRPC Cohort-Part A | Number of Participants Who Discontinued Study Treatment Due to an AE | 2 Participants |
| MK-8628 20 mg NMC Cohort-Part A | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| MK-8628 20 mg TNBC Cohort-Part A | Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
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.
Time frame: From time of first dose until the end of the 30-day follow-up (up to 25 months)
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-8628 20 mg CRPC Cohort-Part A | Number of Participants Who Experienced at Least One Adverse Event (AE) | 9 Participants |
| MK-8628 20 mg NMC Cohort-Part A | Number of Participants Who Experienced at Least One Adverse Event (AE) | 3 Participants |
| MK-8628 20 mg TNBC Cohort-Part A | Number of Participants Who Experienced at Least One Adverse Event (AE) | 1 Participants |
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.
Time frame: Assessed every 6 weeks from time of first dose until disease progression (up to 24 months)
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-8628 20 mg CRPC Cohort-Part A | Objective Response Rate (ORR) | 0 Participants |
| MK-8628 20 mg NMC Cohort-Part A | Objective Response Rate (ORR) | 0 Participants |
| MK-8628 20 mg TNBC Cohort-Part A | Objective Response Rate (ORR) | 0 Participants |
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.
Time frame: Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-8628 20 mg CRPC Cohort-Part A | Observed Maximum Concentration (Cmax) of MK-8628 | 355 ng/mL | Standard Deviation 157 |
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.
Time frame: Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-8628 20 mg CRPC Cohort-Part A | Observed Minimum Concentration (Cmin) of MK-8628 | 111 ng/mL | Standard Deviation 45.9 |
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.
Time frame: Cycle1/Day 1: predose, 20 minutes, 1 hour, 2.25 hours (hrs), 3.25 hrs, 8 hrs, and 12 hrs postdose
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| MK-8628 20 mg CRPC Cohort-Part A | Time to Maximum Concentration (Tmax) of MK-8628 | 2.25 hours |