Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Neoplasms by Histologic Type

Hematologic Diseases

Bone Marrow Diseases

Precancerous Conditions

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

Dermatologic Agents

All Drugs and Chemicals

Tretinoin

Keratolytic Agents

Participants receive bomedemstat 0.75 mg/kg/day orally in 14-day cycles consisting of 7 days of treatment and 7 days of rest. Participants will receive up to 4 cycles (14-day cycles) for up to a total of up 56 days (28 days on treatment).

Participants receive bomedemstat 1.5 mg/kg/day orally in 14-day cycles consisting of 7 days of treatment and 7 days of rest. Participants will receive up to 4 cycles (14-day cycles) for up to a total of up 56 days (28 days on treatment).

Participants receive bomedemstat 3 mg/kg/day orally in 14-day cycles consisting of 7 days of treatment and 7 days of rest. Participants will receive up to 4 cycles (14-day cycles) for up to a total of up 56 days (28 days on treatment).

Participants receive bomedemstat 6 mg/kg/day orally in 14-day cycles consisting of 7 days of treatment and 7 days of rest. Participants will receive up to 4 cycles (14-day cycles) for up to a total of up 56 days (28 days on treatment).

Participants receive bomedemstat 3 mg/kg/day orally plus tretinoin 45 mg/m\^2/day orally in 14-day cycles consisting of 7 days of treatment and 7 days of rest. Participants will receive up to 4 cycles (14-day cycles) for up to a total of up 56 days (28 days on treatment).

Participants receive bomedemstat 6 mg/kg/day orally plus tretinoin 45 mg/m\^2/day orally in 14-day cycles consisting of 7 days of treatment and 7 days of rest. Participants will receive up to 4 cycles (14-day cycles) for up to a total of up 56 days (28 days on treatment).

Participants receive bomedemstat 6 mg/kg/day orally plus tretinoin 45 mg/m\^2/day orally in 21-day cycles consisting of 14 days of treatment and 7 days of rest. Participants will receive up to 2 cycles (21-day cycles) for up to a total of up 42 days (28 days on treatment).

Participants receive bomedemstat 6 mg/kg/day orally for 21 days plus tretinoin 45 mg/m\^2/day orally in 28-day cycles consisting of 21 days of treatment and 7 days of rest. Participants will receive at least 1 cycle (28-day cycles) and will receive subsequent cycles at the discretion of the investigator.

bomedemstat

tretinoin

Medical Director

This is an open label study of the dose and duration of an orally administered lysine-specific demethylase 1 (LSD1) inhibitor, bomedemstat, in patients with high-risk acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). Some participants may also receive all-trans retinoic acid (ATRA; also known as tretinoin and Vesanoid®) in combination with bomedemstat. This study investigates the following:

* The safety and tolerability of bomedemstat with and without ATRA
* The pharmacodynamic effect of different doses of bomedemstat and treatment durations, as well as bomedemstat administered in combination with ATRA
* The pharmacokinetics of bomedemstat with and without ATRA

A Study of Bomedemstat (IMG-7289/MK-3543) With and Without ATRA, in Participants With Advanced Myeloid Malignancies (IMG-7289-CTP-101/MK-3543-001)

A Multi-Center, Open Label Study to Assess the Safety, Steady-State Pharmacokinetics and Pharmacodynamics of IMG-7289 With and Without ATRA (Tretinoin) in Patients With Advanced Myeloid Malignancies

An AE was defined as any undesirable physical, psychological, or behavioral effect experienced by a participant during participation in an investigational study, in conjunction with the use of the drug or biologic, whether or not related to the study drug. This included any untoward signs or symptoms experienced by the participant from the time of first dose until completion of the study. The number of participants who experienced an AE is presented.

An SAE was defined as any adverse event, whether or not related to the study drug, that resulted in any of the following outcomes:

* Death
* Life-threatening experience
* Required or prolonged inpatient hospitalization
* Persistent or significant disability/incapacity
* Congenital anomaly
* Important medical events that, based upon appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes listed above.

The number of participants who experienced an SAE is presented.

An AE was defined as any undesirable physical, psychological, or behavioral effect experienced by a participant during participation in an investigational study, in conjunction with the use of the drug or biologic, whether or not related to the study drug. This included any untoward signs or symptoms experienced by the participant from the time of first dose until completion of the study. The number of participants who discontinued study treatment due to an AE is presented.

DLTs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. A DLT was defined as any of the following events that occurs during the DLT evaluation period and is considered by the Investigator possibly, probably, or definitely related to bomedemstat:

* A clinically significant bleeding event
* Any Grade 4 or 5 non-haematologic adverse event
* Any Grade 3 non-haematologic adverse event with failure to recover to Grade 1 within 7 days of drug cessation, with the following exceptions: ≥ Grade 3 nausea, vomiting or diarrhoea that responds to standard medical care and ≥ Grade 3 aesthenia lasting less than 14 days
* Any Grade 3 electrolyte abnormality unrelated to the underlying malignancy and persisting greater than 24 hours.

Per protocol, DLTs were measured during the first 28-day treatment period. The number of participants who experienced a DLT is presented.

AEs were graded for severity on a scale of 1 to 5 using CTCAE criteria. Grade 1=mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2=moderate, minimal, local, or noninvasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3=severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care. Grade 4=life-threatening consequences with urgent intervention indicated. Grade 5 =death related to AE. The number of participants who experienced any Grade 3 to 5 AE is reported.

Medical Events of Interest (MEOI) were adverse events that did not meet any criteria for a serious adverse event but were of particular interest in the context of the study. MEOIs included bleeding due to low platelets; electrocardiogram (ECG) QT corrected interval prolonged 481-500 milliseconds; and infection where, at a minimum, oral antibiotic, antifungal, or antiviral intervention is indicated. The number of participants with MEOIs is presented.

Cmax was defined as the maximum concentration of bomedemstat observed after administration of bomedemstat alone or administered with tretinoin. Plasma samples were collected at multiple time points to estimate the CMax of bomedemstat using non-compartmental methods of analysis following oral dosing of participants in Cycle 1 (Cycle 1 = 7 days of treatment and 7 days of rest for a total of 14 days). Unbound plasma concentrations of bomedemstat were estimated by assuming that protein binding was 60.57%. For the pharmacokinetic analysis, plasma concentrations below the assay limit of quantitation (LOQ) that occurred from predose to the first concentration ≥LOQ were treated as 0 and those that occured thereafter were treated as missing. The LOQ of the assay was 1 ng/mL. Per protocol, the Cmax was determined for participants in Cohort 1. The LOQ of the assay was 1 ng/mL. The Cmax of bomedemstat in unbound plasma is presented.

Tmax was the time required to reach the maximum concentration of bomedemstat observed after administration of bomedemstat alone or administered with tretinoin. Plasma samples were collected at multiple time points to estimate the TMax of bomedemstat using non-compartmental methods of analysis following oral dosing of participants in Cycle 1 (Cycle 1 = 7 days of treatment and 7 days of rest for a total of 14 days). For the pharmacokinetic analysis, plasma concentrations below the assay limit of quantitation (LOQ) that occurred from predose to the first concentration ≥LOQ were treated as 0 and those that occured thereafter were treated as missing. The LOQ of the assay was 1 ng/mL. Per protocol, the Tmax was determined for participants in Cohort 1. The Tmax of bomedemstat in plasma is presented.

AUC0-24hr was defined as the total exposure of bomedemstat over 24 hours after administration of bomedemstat alone or administered with tretinoin. Plasma samples were collected at multiple time points to estimate the AUC 0-24hr of bomedemstat using non-compartmental methods of analysis following oral dosing of participants in Cycle 1 (Cycle 1 = 7 days of treatment and 7 days of rest for a total of 14 days). Unbound plasma concentrations of bomedemstat were estimated by assuming that protein binding was 60.57%. For the pharmacokinetic analysis, plasma concentrations below the assay limit of quantitation (LOQ) that occurred from predose to the first concentration ≥LOQ were treated as 0 and those that occured thereafter were treated as missing. The LOQ of the assay was 1 ng/mL. Per protocol, the AUC 0-24hr was determined for participants in Cohort 1. The AUC 0-24hr of bomedemstat in unbound plasma is presented.

t1/2 was the time required to divide the bomedemstat concentration by two after reaching pseudo-equilibrium after administration of bomedemstat alone or administered with tretinoin. Plasma samples were collected at multiple time points to estimate the t1/2 of bomedemstat using non-compartmental methods of analysis following oral dosing of participants in Cycle 1 (Cycle 1 = 7 days of treatment and 7 days of rest for a total of 14 days). For the pharmacokinetic analysis, plasma concentrations below the assay limit of quantitation (LOQ) that occurred from predose to the first concentration ≥LOQ were treated as 0 and those that occured thereafter were treated as missing. The LOQ of the assay was 1 ng/mL. Per protocol, the t1/2 was determined for participants in Cohort 1. The t1/2 of bomedemstat in plasma is presented.

CL/F was the volume of plasma from which bomedemstat was eliminated per unit of time after administration of bomedemstat alone or administered with tretinoin. Plasma samples were collected at multiple time points to estimate the CL/F of bomedemstat using non-compartmental methods of analysis following oral dosing of participants in Cycle 1 (Cycle 1 = 7 days of treatment and 7 days of rest for a total of 14 days). For the pharmacokinetic analysis, plasma concentrations below the assay limit of quantitation (LOQ) that occurred from predose to the first concentration ≥LOQ were treated as 0 and those that occured thereafter were treated as missing. The LOQ of the assay was 1 ng/mL. Per protocol, the CL/F was determined for participants in Cohort 1. The CL/F of bomedemstat in plasma is presented.

Vz/F was the volume of distribution of bomedemstat during the terminal phase after administration of bomedemstat alone or administered with tretinoin. Plasma samples were collected at multiple time points to estimate the Vz/F of bomedemstat using non-compartmental methods of analysis following oral dosing of participants in Cycle 1 (Cycle 1 = 7 days of treatment and 7 days of rest for a total of 14 days). For the pharmacokinetic analysis, plasma concentrations below the assay limit of quantitation (LOQ) that occurred from predose to the first concentration ≥LOQ were treated as 0 and those that occured thereafter were treated as missing. The LOQ of the assay was 1 ng/mL. Per protocol, the Vz/F was determined for participants in Cohort 1. The Vz/F of bomedemstat in plasma is presented.

kel was the rate at which bomedemstat was removed from the body by excretion or metabolism after administration of bomedemstat alone or administered with tretinoin. Plasma samples were collected at multiple time points to estimate the kel of bomedemstat using non-compartmental methods of analysis following oral dosing of participants in Cycle 1 (Cycle 1 = 7 days of treatment and 7 days of rest for a total of 14 days). kel was obtained from the slope of the line, fitted by linear least squares regression, through the terminal points of the log (base e) concentration-time profiles. For the pharmacokinetic analysis, plasma concentrations below the assay limit of quantitation (LOQ) that occurred from predose to the first concentration ≥LOQ were treated as 0 and those that occured thereafter were treated as missing. The LOQ of the assay was 1 ng/mL. Per protocol, the kel was determined for participants in Cohort 1. The kel of bomedemstat in plasma is presented.

EFS was defined as the time from the first dose of study treatment to the date of a documented EFS event of resistance, relapse, progression, or death due to any cause as assessed by the investigator. Participants without documented events were censored at the date of the last disease assessment. The EFS, calculated using the Kaplan-Meier method, is presented.

OS was defined as the time from the first dose of study treatment until death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. The OS, calculated using the Kaplan-Meier method, is presented.

ORR was the percentage of participants with a response of complete remission (CR), CR with incomplete recovery (Cri), morphologic leukaemia-free state (MLFS), partial remission (PR), cytogenetic CR (CRc), molecular CR (CRm), or stable disease (SD):

* CR: \<5% bone marrow (BM) blasts or blasts with Auer rods; no extramedullary disease (EMD); absolute neutrophil count ≥1000/μL; platelets ≥100,000/μL; independent of transfusion
* Cri: CR with residual neutropenia (\<1,000/μL) or thrombocytopenia (\<100,000/μL); no EMD; does not require transfusion independence (TI)
* MLFS: \<5% blasts in BM with marrow spicules; no EMD; does not require TI
* PR: ≥ 50% decrease in BM blasts to a range of 5%-25%; Neutrophils ≥ 1,000/μL; Platelets ≥ 100,000/μL; independent of transfusion. ≤ 5% blasts is PR if Auer rods present
* CRc: CR+reversion to a normal karyotype if initially abnormal
* CRm: CR+no evidence of residual disease by molecular testing
* SD: No evidence of CR, PR, progression, new dysplastic changes

BOR was the percentage of participants with a best overall response of CR, Cri, MLFS, PR, CRc, CRm, or SD:

* CR: \<5% bone marrow (BM) blasts or blasts with Auer rods; no extramedullary disease (EMD); absolute neutrophil count ≥1000/μL; platelets ≥100,000/μL; independent of transfusion
* Cri: CR with residual neutropenia (\<1,000/μL) or thrombocytopenia (\<100,000/μL); no EMD; does not require transfusion independence (TI)
* MLFS: \<5% blasts in BM with marrow spicules; no EMD; does not require TI
* PR: ≥ 50% decrease in BM blasts to a range of 5%-25%; Neutrophils ≥ 1,000/μL; Platelets ≥ 100,000/μL; independent of transfusion. ≤ 5% blasts is PR if Auer rods present
* CRc: CR+reversion to a normal karyotype if initially abnormal
* CRm: CR+no evidence of residual disease by molecular testing
* SD: No evidence of CR, PR, progression, new dysplastic changes

ORR was the percentage of participants with a response of complete remission (CR), partial remission (PR), marrow CR (CRm), cytogenetic response (CyR), or stable disease (SD) lasting for ≥4 weeks:

* CR: ≤5% myeloblasts in the bone marrow (BM) with normal maturation of all cell lines; persistent dysplasia will be noted; Hgb ≥11 g/dL, Platelets ≥100 X 10\^9/L, Neutrophils ≥1.0 X 10\^9/L, and 0% Blasts in the peripheral blood
* PR: All CR criteria if abnormal before treatment except: BM blasts decreased by ≥50% over pretreatment but still \>5%. Cellularity and morphology not relevant
* CRm: ≤ 5% myeloblasts in BM and decrease by ≥50% over pretreatment. Hematological improvement responses in the peripheral blood will be noted in addition to bone marrow CR.
* CyR: Complete=Disappearance of the chromosomal abnormality without appearance of new ones. Partial= ≥50% reduction of the chromosomal abnormality
* SD: Failure to achieve at least PR, but no evidence of progression for \>8 weeks

BOR was the percentage of participants with a best overall response of CR, PR, CRm, CyR, or SD lasting for ≥4 weeks:

* CR: ≤5% myeloblasts in the bone marrow (BM) with normal maturation of all cell lines; persistent dysplasia will be noted; Hgb ≥11 g/dL, Platelets ≥100 X 10\^9/L, Neutrophils ≥1.0 X 10\^9/L, and 0% Blasts in the peripheral blood
* PR: All CR criteria if abnormal before treatment except: BM blasts decreased by ≥50% over pretreatment but still \>5%. Cellularity and morphology not relevant
* CRm: ≤ 5% myeloblasts in BM and decrease by ≥50% over pretreatment. Hematological improvement responses in the peripheral blood will be noted in addition to bone marrow CR.
* CyR: Complete=Disappearance of the chromosomal abnormality without appearance of new ones. Partial= ≥50% reduction of the chromosomal abnormality
* SD: Failure to achieve at least PR, but no evidence of progression for \>8 weeks

Whole blood samples were collected at time intervals during the first 4 cycles (Cycle length = 7 days of treatment and 7 days of rest for a total of 14 days), which corresponds to 28 days on treatment. The percent change from baseline in erythrocyte count was measured. Baseline was the erythrocyte count at screening or the last available observation prior to the first dose of study drug. An analysis of treatment effect between the doses was determined using a Kruskal-Wallis test. This analysis was done to support the evaluation of plasma concentrations (Cmax and Cmin) and exposure (AUC) on haematopoiesis. Per protocol, the analysis was pre-specified to be done on participants that received bomedemstat alone. The maximum percent change from baseline in erythrocyte count is presented.

Whole blood samples were collected at time intervals during the first 4 cycles (Cycle length = 7 days of treatment and 7 days of rest for a total of 14 days), which corresponds to 28 days on treatment. The percent change from baseline in neutrophil count was measured. Baseline was the neutrophil count at screening or the last available observation prior to the first dose of study drug. An analysis of treatment effect between the doses was determined using a Kruskal-Wallis test. This analysis was done to support the evaluation of plasma concentrations (Cmax and Cmin) and exposure (AUC) on haematopoiesis. Per protocol, the analysis was pre-specified to be done on participants that received bomedemstat alone. The maximum percent change from baseline in neutrophil count is presented.

Whole blood samples were collected at time intervals during the first 4 cycles (Cycle length = 7 days of treatment and 7 days of rest for a total of 14 days), which corresponds to 28 days on treatment. The percent change from baseline in platelet count was measured. Baseline was the platelet count at screening or the last available observation prior to the first dose of study drug. An analysis of treatment effect between the doses was determined using a Kruskal-Wallis test. This analysis was done to support the evaluation of plasma concentrations (Cmax and Cmin) and exposure (AUC) on haematopoiesis. Per protocol, the analysis was pre-specified to be done on participants that received bomedemstat alone. The maximum percent change from baseline in platelet count is presented.

Whole blood samples were collected at time intervals during the first 4 cycles (Cycle length = 7 days of treatment and 7 days of rest for a total of 14 days), which corresponds to 28 days on treatment. The percent change from baseline in reticulocyte count was measured. Baseline was the reticulocyte count at screening or the last available observation prior to the first dose of study drug. An analysis of treatment effect between the doses was determined using a Kruskal-Wallis test. This analysis was done to support the evaluation of plasma concentrations (Cmax and Cmin) and exposure (AUC) on haematopoiesis. Per protocol, the analysis was pre-specified to be done on participants that received bomedemstat alone. The maximum percent change from baseline in reticulocyte count is presented.

Whole blood samples were collected at time intervals during the first 4 cycles (Cycle length = 7 days of treatment and 7 days of rest for a total of 14 days), which corresponds to 28 days on treatment. The percent change from baseline in the number of blasts was measured. Baseline was the number of blasts at screening or the last available observation prior to the first dose of study drug. An analysis of treatment effect between the doses was determined using a Kruskal-Wallis test. This analysis was done to support the evaluation of plasma concentrations (Cmax and Cmin) and exposure (AUC) on haematopoiesis. Per protocol, the analysis was pre-specified to be done on participants that received bomedemstat alone. The maximum percent change from baseline in the number of blasts is presented.

Whole blood samples were collected at time intervals during the first 4 cycles (Cycle length = 7 days of treatment and 7 days of rest for a total of 14 days), which corresponds to 28 days on treatment. The percent change from baseline in the hemoglobin level was measured. Baseline was the hemoglobin level at screening or the last available observation prior to the first dose of study drug. An analysis of treatment effect between the doses was determined using a Kruskal-Wallis test. This analysis was done to support the evaluation of plasma concentrations (Cmax and Cmin) and exposure (AUC) on haematopoiesis. Per protocol, the analysis was pre-specified to be done on participants that received bomedemstat alone. The maximum percent change from baseline in hemoglobin level is presented.

Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)

All-cause mortality was reported on all allocated participants. Serious and non-serious adverse events (AEs) were reported on all participants who received ≥1 dose of study treatment. Progression of underlying malignancy was not reported as an AE if it is consistent with the suspected progression of the underlying cancer.

Participants received bomedemstat 0.75 mg/kg/day orally in 14-day cycles consisting of 7 days of treatment and 7 days of rest. Participants received up to 4 cycles (14-day cycles) for up to a total of up 56 days (28 days on treatment).

Cohort 1a: Bomedemstat 0.75 mg/kg/Day

Participants received bomedemstat 1.5 mg/kg/day orally in 14-day cycles consisting of 7 days of treatment and 7 days of rest. Participants received up to 4 cycles (14-day cycles) for up to a total of up 56 days (28 days on treatment).

Cohort 1b: Bomedemstat 1.5 mg/kg/Day

Participants received bomedemstat 3 mg/kg/day orally in 14-day cycles consisting of 7 days of treatment and 7 days of rest. Participants received up to 4 cycles (14-day cycles) for up to a total of up 56 days (28 days on treatment).

Cohort 1c: Bomedemstat 3 mg/kg/Day

Participants received bomedemstat 6 mg/kg/day orally in 14-day cycles consisting of 7 days of treatment and 7 days of rest. Participants received up to 4 cycles (14-day cycles) for up to a total of up 56 days (28 days on treatment).

Cohort 1d: Bomedemstat 6 mg/kg/Day

Participants received bomedemstat 3 mg/kg/day orally plus tretinoin 45 mg/m\^2/day orally in 14-day cycles consisting of 7 days of treatment and 7 days of rest. Participants received up to 4 cycles (14-day cycles) for up to a total of up 56 days (28 days on treatment).

Cohort 1x3: Bomedemstat 3 mg/kg/Day Orally Plus Tretinoin 45 mg/m^2/Day

Participants received bomedemstat 6 mg/kg/day orally plus tretinoin 45 mg/m\^2/day orally in 14-day cycles consisting of 7 days of treatment and 7 days of rest. Participants received up to 4 cycles (14-day cycles) for up to a total of up 56 days (28 days on treatment).

Cohort 1x6: Bomedemstat 6 mg/kg/Day Plus Tretinoin 45 mg/m^2/Day

Participants received bomedemstat 6 mg/kg/day orally plus tretinoin 45 mg/m\^2/day orally in 21-day cycles consisting of 14 days of treatment and 7 days of rest. Participants received up to 2 cycles (21-day cycles) for up to a total of up 42 days (28 days on treatment).

Cohort 3x: Bomedemstat 6 mg/kg/Day Plus Tretinoin 45 mg/m^2/Day

Participants received bomedemstat 6 mg/kg/day orally for 21 days plus tretinoin 45 mg/m\^2/day orally in 28-day cycles consisting of 21 days of treatment and 7 days of rest. Participants received at least 1 cycle (28-day cycles) and received subsequent cycles at the discretion of the investigator.

Cohort 4x: Bomedemstat 6 mg/kg/Day Plus Tretinoin 45 mg/m^2/Day

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

A diagnosis of either acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) was a requirement for inclusion in this study.

Disease Diagnosis

All participants who received ≥1 dose of study treatment

Senior Vice President, Global Clinical Development

Number of Participants Who Experienced an Adverse Event (AE)

Number of Participants Who Experienced a Serious Adverse Event (SAE)

Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

The DLT population included all participants who received ≥ 1 dose of study treatment and had follow-up through the DLT evaluation period (28 days on treatment) or who discontinued from study treatment due a to drug-related AE.

Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)

Number of Participants Experiencing Any Grade 3 to 5 Adverse Events (AE) as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03

Number of Participants Who Experienced a Medical Event of Interest (MEOI)

Cycle 1 Day 1

Cycle 1 Day 7

The analysis population consisted of all participants from Cohort 1 who received ≥1 dose of bomedemstat alone or administered with tretinoin and who had available data for the analysis of Cmax.

Maximum Concentration (Cmax) of Bomedemstat Alone or Administered With Tretinoin

The analysis population consisted of all participants from Cohort 1 who received ≥1 dose of bomedemstat alone or administered with tretinoin and who had available data for the analysis of Tmax.

Time to Maximum Concentration (Tmax) of Bomedemstat Alone or Administered With Tretinoin

The analysis population consisted of all participants from Cohort 1 who received ≥1 dose of bomedemstat alone or administered with tretinoin and who had available data for the analysis of AUC0-24hr.

Area Under the Concentration Time Curve From Time 0 to 24 Hours (AUC0-24hr) Postdose of Bomedemstat Alone or Administered With Tretinoin

The analysis population consisted of all participants from Cohort 1 who received ≥1 dose of bomedemstat alone or administered with tretinoin and who had available data for the analysis of t1/2.

Elimination Half Life (t1/2) of Bomedemstat Alone or Administered With Tretinoin

The analysis population consisted of all participants from Cohort 1 who received ≥1 dose of bomedemstat alone or administered with tretinoin and who had available data for the analysis of CL/F.

Apparent Total Body Clearance (CL/F) of Bomedemstat Alone or Administered With Tretinoin

The analysis population consisted of all participants from Cohort 1 who received ≥1 dose of bomedemstat alone or administered with tretinoin and who had available data for the analysis of Vz/F.

Volume of Distribution (Vz/F) of Bomedemstat Alone or Administered With Tretinoin

The analysis population consisted of all participants from Cohort 1 who received ≥1 dose of bomedemstat alone or administered with tretinoin and who had available data for the analysis of kel.

Terminal Elimination Rate Constant (Kel) of Bomedemstat Alone or Administered With Tretinoin

All participants with high-risk AML as defined by the protocol, who received ≥1 dose of bomedemstat, had disease assessment at baseline, and had data available for the analysis.

Event-free Survival (EFS) For High-risk Acute Myeloid Leukemia (AML) Participants

All participants with high-risk MDS as defined by the protocol, who received ≥1 dose of bomedemstat, had disease assessment at baseline, and had data available for the analysis.

Event-free Survival (EFS) For High-risk Myelodysplastic Syndromes (MDS) Participants

Overall Survival (OS) For High-risk Acute Myeloid Leukemia (AML) Participants

Overall Survival (OS) For High-risk Myelodysplastic Syndromes (MDS) Participants

Objective Response Rate (ORR) For High-risk Acute Myeloid Leukemia (AML) Participants Determined Using the Revised/Modified International Working Group (IWG) Response Criteria (Cheson et al., 2003) and Assessed by the Investigator

Complete remission (CR)

CR with incomplete recovery (CRi)

Morphologic leukaemia-free state (MLFS)

Partial remission (PR)

Cytogenetic CR (CRc)

Molecular CR (CRm)

Stable disease (SD)

Best Overall Response (BOR) For High-risk Acute Myeloid Leukemia (AML) Participants Determined Using the Revised/Modified International Working Group (IWG) Response Criteria (Cheson et al., 2003) and Assessed by the Investigator

Objective Response Rate (ORR) For High-risk Myelodysplastic Syndromes (MDS) Participants Determined Using the Revised/Modified International Working Group (IWG) Response Criteria (Cheson et al., 2006) and Assessed by the Investigator

Marrow CR (CRm)

Cytogenetic response (CyR)

Best Overall Response (BOR) Assessed by the Revised/Modified International Working Group (IWG) Response Criteria (Cheson et al., 2006): High-risk Myelodysplastic Syndromes (MDS) Participants

The analysis population consisted of all participants from Cohort 1 who received ≥1 dose of bomedemstat alone and who had available data for the analysis.

Spots Global Cancer Trial Database for A Study of Bomedemstat (IMG-7289/MK-3543) With and Without ATRA, in Participants With Advanced Myeloid Malignancies (IMG-7289-CTP-101/MK-3543-001)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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