Neoplasms

Blood and Lymph Conditions

All Conditions

Heart and Blood Diseases

Rare Diseases

Polycythemia Vera

Polycythemia

Primary Myelofibrosis

Thrombocytosis

Thrombocythemia, Essential

Myeloproliferative Disorders

Bone Marrow Diseases

Hematologic Diseases

Bone Marrow Neoplasms

Hematologic Neoplasms

Blood Platelet Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Essential Thrombocythemia

Chronic Myeloproliferative Disorders

In the Phase 1/2a portion of the study, PMF participants received 0.25 mg/kg/d bomedemstat orally every day (qd) for 85 days during the Initial Treatment Period (ITP). Qualifying participants could continue to receive treatment for an additional 85 days during an Additional Treatment Period (ATP) as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.

In the Phase 1/2a portion of the study, PPV-MF participants received 0.25 mg/kg/d bomedemstat orally qd for 85 days during the ITP. Qualifying participants could continue to receive treatment for an additional 85 days during an ATP as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.

In the Phase 1/2a portion of the study, PET-MF participants received 0.25 mg/kg/d bomedemstat orally qd for 85 days during the ITP. Qualifying participants could continue to receive treatment for an additional 85 days during an ATP as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.

In the Phase 2b portion of the study, PMF participants received 0.5 mg/kg/d bomedemstat orally qd for 169 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during an ATP as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.

In the Phase 2b portion of the study, PPV-MF participants received 0.5 mg/kg/d bomedemstat orally qd for 169 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during an ATP as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.

In the Phase 2b portion of the study, PET-MF participants received 0.5 mg/kg/d bomedemstat orally qd for 169 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during an ATP as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.

In the Phase 2b portion of the study, PMF participants received 0.6 mg/kg/d bomedemstat orally qd for 169 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during an ATP as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.

In the Phase 2b portion of the study, PPV-MF participants received 0.6 mg/kg/d bomedemstat orally qd for 169 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during an ATP as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.

In the Phase 2b portion of the study, PET-MF participants received 0.6 mg/kg/d bomedemstat orally qd for 169 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during an ATP as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.

Oral (capsule) administration according to dose allocation.

Bomedemstat

Medical Director

This is a Phase 1/2 open-label study to evaluate the safety, tolerability, steady-state pharmacokinetic (PK) and pharmacodynamics (PD) of a lysine-specific demethylase 1 (LSD1) inhibitor, bomedemstat (IMG-7289/MK-3543), administered orally once daily in participants with myelofibrosis.

The primary hypothesis is that bomedemstat is a safe and tolerable orally available agent when administered to participants with myelofibrosis including primary myelofibrosis (PMF), post-polycythaemia vera-myelofibrosis (PPVMF), and post-essential thrombocythaemia-myelofibrosis (PET-MF) (collectively referred to as 'MF'); inhibition of LSD1 by bomedemstat will reduce spleen size in those with splenomegaly, improve haematopoiesis and reduce constitutional symptoms associated with these disorders.

This study initiated as a Phase 1/2a study assessing the safety of the starting dose, an 85-day duration of treatment, and the PK and PD effects of bomedemstat, with transition to a Phase 2b study incorporating changes supported by the Phase 1/2a data.

Bomedemstat (IMG-7289/MK-3543) in Participants With Myelofibrosis (IMG-7289-CTP-102/MK-3543-002)

A Multi-Center, Open Label Study to Assess the Safety, Steady-State Pharmacokinetics and Pharmacodynamics of IMG-7289 in Patients With Myelofibrosis

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

DLT was defined as any one of the following adverse events (AEs) that occured through Day 7 of the Initial Treatment Period (ITP) and was considered by the Investigator to be possibly, probably or definitely related to bomedemstat:

* Thrombocytopenia leading to clinically significant sequelae (i.e., a clinically significant bleeding event or the need for prophylactic transfusions)
* A clinically significant bleeding event in a participant with a platelet count \>50 x 10\^9/L (50 k/μL)
* Any Grade 4 or 5 non-haematologic adverse event
* Any Grade 3 non-haematologic adverse event with failure to recover to Grade 2 within 7 days of drug cessation, with the following exceptions: ≥ Grade 3 nausea, vomiting or diarrhea that responds to standard medical care; ≥ Grade 3 aesthenia lasting less than 14 days; any Grade 3 electrolyte abnormality unrelated to the underlying malignancy and persisting greater than 24 hours.

The number of participants with a DLT were reported.

An AE was any undesirable physical, psychological or behavioral effect experienced by a participant, in conjunction with the use of the drug or biologic, whether or not product-related. This included any untoward signs or symptoms experienced by the participant from the time of first dose with bomedemstat until completion of the study. Serious AEs (SAEs) were any AE that resulted in death, life-threatening experience, required or prolonged inpatient hospitalization, persistent or significant disability/incapacity, congenital anomaly, or important medical events. The number of participants with at least one treatment-emergent (TE) SAE was reported for each arm.

An AE was any undesirable physical, psychological or behavioral effect experienced by a participant, in conjunction with the use of the drug or biologic, whether or not product-related. This included any untoward signs or symptoms experienced by the participant from the time of first dose with bomedemstat until completion of the study. The number of participants with at least one TE AE was reported for each arm.

An AE was any undesirable physical, psychological or behavioral effect experienced by a participant, in conjunction with the use of the drug or biologic, whether or not product-related. This included any untoward signs or symptoms experienced by the participant from the time of first dose with bomedemstat until completion of the study. The number of participants that discontinued study treatment with bomedemstat due to a TE AE was reported for each arm.

Cmax was defined as the maximum observed concentration after administration obtained directly from the concentration time profile. Blood and plasma samples were collected at pre-specified timepoints to calculate Cmax in participants of the Phase 1/2a portion of the study. As pre-specified by the protocol and Pharmacokinetic Analysis Plan (PAP), Phase 2b participants were excluded from this analysis.

Tmax was defined as the time to maximum concentration after administration obtained by inspection. Blood and plasma samples were collected at pre-specified timepoints to calculate Tmax in participants of the Phase 1/2a portion of the study. As pre-specified by the protocol and Pharmacokinetic Analysis Plan (PAP), Phase 2b participants were excluded from this analysis.

AUC0-24 was defined as the area under the concentration versus time curve calculated using the linear trapezoidal rule from the zero time-point to the 24-hour time-point concentration. Blood and plasma samples were collected at pre-specified timepoints to calculate AUC0-24 in participants of the Phase 1/2a portion of the study. As pre-specified by the protocol and Pharmacokinetic Analysis Plan (PAP), Phase 2b participants were excluded from this analysis.

CL/F was defined as the apparent total clearance of drug after oral administration. Blood and plasma samples were collected at pre-specified timepoints to calculate CL/F in participants of the Phase 1/2a portion of the study. As pre-specified by the protocol and Pharmacokinetic Analysis Plan (PAP), Phase 2b participants were excluded from this analysis.

Change in spleen volume was assessed based on calculated spleen volume (ml) measured by magnetic resonance imaging (MRI), or computerized tomography (CT) scan (where locally permitted) if the participant was not a candidate for MRI from Day 0. Percentage change from baseline in spleen volume was reported at Initial Treatment Period (ITP) Day 84, ITP Day 168, Additional Treatment Period 1 (ATP1) Day 84 (Study Day 253), and ATP1 Day 168 (Study Day 337).

Change in spleen size was assessed based on spleen palpation (in cm) at each visit. Percentage change from baseline in spleen size was reported at ITP Day 84, ITP Day 168, ATP1 Day 84 (Study Day 253), ATP1 Day 168 (Study Day 337), ATP2 Day 84 (Study Day 422), ATP2 Day 168 (Study Day 506), and ATP3 Day 84 (Study Day 591). As prespecified by the Statistical Analysis Plan, assessments for the Phase 1/2 groups were summarized using visit windowing after the Day 84 visit of the ITP to allow for comparison with the Phase 2b groups at ITP Day 168.

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

All-Cause Mortality table includes all allocated participants. Serious and Non-serious adverse events (AEs) tables include all allocated participants who received at least 1 dose of study drug.

In the Phase 1/2a portion of the study, PMF participants received 0.25 mg/kg/d bomedemstat orally every day (qd) for 85 days during the Initial Treatment Period (ITP). Qualifying participants could continue to receive treatment for an additional 169 days during the Additional Treatment Period (ATP) as determined by the investigator.

Ph 1/2a PMF: Bomedemstat 0.25 mg/kg/d

In the Phase 1/2a portion of the study, PPV-MF participants received 0.25 mg/kg/d bomedemstat orally qd for 85 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during the ATP as determined by the investigator.

Ph 1/2a PPV-MF: Bomedemstat 0.25 mg/kg/d

In the Phase 1/2a portion of the study, PET-MF participants received 0.25 mg/kg/d bomedemstat orally qd for 85 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during the ATP as determined by the investigator.

Ph 1/2a PET-MF: Bomedemstat 0.25 mg/kg/d

In the Phase 2b portion of the study, PMF participants received 0.5 mg/kg/d bomedemstat orally qd for 169 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during the ATP as determined by the investigator.

Ph 2b PMF: Bomedemstat 0.5 mg/kg/d

In the Phase 2b portion of the study, PPV-MF participants received 0.5 mg/kg/d bomedemstat orally qd for 169 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during the ATP as determined by the investigator.

Ph 2b PPV-MF: Bomedemstat 0.5 mg/kg/d

In the Phase 2b portion of the study, PET-MF participants received 0.5 mg/kg/d bomedemstat orally qd for 169 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during the ATP as determined by the investigator.

Ph 2b PET-MF: Bomedemstat 0.5 mg/kg/d

In the Phase 2b portion of the study, PMF participants received 0.6 mg/kg/d bomedemstat orally qd for 169 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during the ATP as determined by the investigator.

Ph 2b PMF: Bomedemstat 0.6 mg/kg/d

In the Phase 2b portion of the study, PPV-MF participants received 0.6 mg/kg/d bomedemstat orally qd for 169 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during the ATP as determined by the investigator.

Ph 2b PPV-MF: Bomedemstat 0.6 mg/kg/d

In the Phase 2b portion of the study, PET-MF participants received 0.6 mg/kg/d bomedemstat orally qd for 169 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during the ATP as determined by the investigator.

Ph 2b PET-MF: Bomedemstat 0.6 mg/kg/d

In the Phase 1/2a portion of the study, PMF participants received 0.25 mg/kg/d bomedemstat orally qd for 85 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during the ATP as determined by the investigator.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

American Indian or Alaska Native

Asian

Black or African American

Native Hawaiian or Other Pacific Islander

White

Other

Multiple

Not Reported

Race/Ethnicity, Customized

Senior Vice President, Global Clinical Development

All participants receiving at least one dose of bomedemstat were included in the DLT analysis.

Number of Participants With Dose Limiting Toxicities (DLTs)

All participants receiving at least one dose of bomedemstat were included in the safety analysis.

Number of Participants With Serious Adverse Events

Number of Participants With Adverse Events

Number of Participants That Discontinued Study Treatment Due To AEs

Plasma

Blood

In the Phase 1/2a portion of the study, participants received 0.25 mg/kg/d bomedemstat orally qd for 85 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during the ATP as determined by the investigator.

Ph 1/2a Portion: Bomedemstat 0.25 mg/kg/d

As pre-specified by the PAP, all participants in the Phase 1/2a portion of the study who received bomedemstat and completed a sufficient portion of the study with enough data for the determination of pharmacokinetic parameters were analyzed. For the purposes of the analysis, Phase 1/2a participants were analyzed irrespective of myelofibrosis disorder (PMF, PPV-MF, or PET-MF) per protocol. Phase 2b participants were excluded from this analysis.

Phase 1/2a Portion: Observed Maximum Concentration (Cmax) of Bomedemstat

Phase 1/2a Portion: Time to Maximum Concentration (Tmax) of Bomedemstat

Phase 1/2a Portion: Area Under the Concentration-time Curve of Bomedemstat From Time 0 to 24 Hours Post-dose (AUC0-24)

As pre-specified by the PAP, only participants in the Phase 1/2a portion of the study who received bomedemstat and completed a sufficient portion of the study with enough data for the determination of pharmacokinetic parameters were analyzed. For the purposes of the analysis, Phase 1/2a participants were analyzed irrespective of myelofibrosis disorder (PMF, PPV-MF, or PET-MF) per protocol. Phase 2b participants were excluded from this analysis.

Phase 1/2a Portion: Apparent Total Clearance (CL/F) of Bomedemstat After Oral Administration

ITP Day 84 (Study Day 84)

ITP Day 168 (Study Day 168)

ATP1 Day 84 (Study Day 253)

ATP1 Day 168 (Study Day 337)

All allocated participants who received at least one dose of treatment and had available spleen volume data.

Percentage Change From Baseline in Spleen Volume

ATP2 Day 84 (Study Day 422)

ATP2 Day 168 (Study Day 506)

ATP3 Day 84 (Study Day 591)

All allocated participants who received at least one dose of treatment and had available spleen size data.

Percentage Change From Baseline in Spleen Size

Overall Study

Symptoms and General Pathology

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Neoplasms by Histologic Type

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

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.

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

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

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Bomedemstat (IMG-7289/MK-3543) in Participants With Myelofibrosis (IMG-7289-CTP-102/MK-3543-002)	NCT03136185	Myelofibrosis Post-polycythem... Post-essential ... Primary Myelofi...	Bomedemstat	18 Years -	Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)
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)	NCT02842827	Acute Myeloid L... Myelodysplastic...	bomedemstat tretinoin	18 Years -	Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)
Extension Study of Bomedemstat (IMG-7289/MK-3543) in Participants With Myeloproliferative Neoplasms (IMG-7289-CTP-202/MK-3543-005)	NCT05223920	Thrombocythemia... Primary Myelofi...	Bomedemstat	18 Years -	Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)
Bomedemstat and Maintenance Immunotherapy for Treatment of Newly Diagnosed Extensive Stage Small Cell Lung Cancer	NCT05191797	Extensive Stage... Limited Stage L...	Bomedemstat Atezolizumab	18 Years -	University of Washington
Venetoclax and Bomedemstat in Patients With Relapsed/Refractory Acute Myeloid Leukemia	NCT05597306	Acute Myeloid L... Refractory Acut... Acute Myeloid L...	Bomedemstat Venetoclax	18 Years -	University of Miami
A Study to Evaluate Safety and Efficacy of Bomedemstat (MK-3543-017)	NCT06351631	Thrombocythemia... Primary Myelofi... Myelofibrosis Post-polycythem... Post-essential ... Polycythemia Ve...	Bomedemstat	18 Years -	Merck Sharp & Dohme LLC
A Study of Bomedemstat (MK-3543) in Participants With Polycythemia Vera (MK-3543-004)	NCT05558696	Polycythemia Ve...	bomedemstat	18 Years -	Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)
A Study of Bomedemstat (MK-3543) in Participants With Polycythemia Vera (MK-3543-004)	NCT05558696	Polycythemia Ve...	bomedemstat	18 Years -	Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)

Spots Global Cancer Trial Database for bomedemstat

Every month we try and update this database with for bomedemstat cancer trials from around the world to help patients and their families find trials that might be right for them.
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Spots Global Cancer Trial Database for bomedemstat

Every month we try and update this database with for bomedemstat cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for bomedemstat cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.