Bomedemstat (IMG-7289) Plus Ruxolitinib for Myelofibrosis | NCT05569538

Status Module

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

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Cohort A (Patients refractory to, relapsed or intolerant of ruxolitinib):	Experimental	Bomedemstat : The starting dose of bomedemstat at Initial Treatment Period Cycle 1 Day 1 will be 0.4 mg/kg daily for all patients in Cohort A. The first up-titration is not permitted until Initial Treatment Period Cycle 2 Day 1; thereafter, the dose may be up-titrated no more frequently than every 4 weeks from the prior up- or down-titration (note: down-titrations may occur at any time (or the current dose maintained) in the best interest and safety of the patient), to a target platelet count range of 50-100 x 10^9/L. Ruxolitinib: Patients will continue their prior, stable dose of ruxolitinib. This same dose will be continued throughout the study unless dose modification is required because of toxicity.	Drug: Bomedemstat
Cohort B (Cohort B will consist of 10 patients who are JAK inhibitor naïve):	Experimental	Bomedemstat: The starting dose of bomedemstat at Initial Treatment Period Cycle 1 Day 1 will be 0.4 mg/kg daily for all patients in Cohort B. The first up-titration is not permitted until Initial Treatment Period Cycle 2 Day 1; thereafter, the dose may be up-titrated no more frequently than every 4 weeks from the prior up- or down-titration (note: down-titrations may occur at any time (or the current dose maintained) in the best interest and safety of the patient), to a target platelet count range of 50-100 x 10^9/L. Ruxolitinib: Patients will start treatment with ruxolitinib at Initial Treatment Period Cycle 1 Day 1. The starting dose of ruxolitinib will be 10 mg BID. This same dose will be continued throughout the study unless dose modification is required because of toxicity.	Drug: Bomedemstat

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Bomedemstat	Drug	Bomedemstat will be self-administered orally once daily. In both cohorts, the dose of bomedemstat will be adjusted in each patient based on titration of the patient's platelet count to the target range. Ruxolitinib will be self-administered orally. Both medications will continue uninterrupted in 28-day cycles. Subjects will continue combination treatment through the Initial Treatment Period (first 6 cycles), which includes a Qualification Assessment. Those deriving clinical benefit in the opinion of the treating physician may continue receiving combination treatment in the Additional Treatment Period (6 cycles). Qualification Assessments will be performed at the end of each Additional Treatment Period, which is iterative, and may repeat for as long as clinical benefit is sustained, at the discretion of the treating physician.

Measure	Description	Time Frame
Adverse events	Enumeration and description of adverse events (AEs), including determination of dose limiting toxicities (DLTs), serious adverse events (SAEs), and other AEs	24 months

Measure	Description	Time Frame
Spleen response at 24 weeks	Proportion of patients who experience a spleen length reduction by palpation of ≥30% OR spleen volume reduction (SVR) of ≥35% by MRI or CT by 24 weeks of treatment	24 weeks
Symptom response at 24 weeks

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Cohort A:

1. Patients refractory to, relapsed or intolerant of ruxolitinib as per one of the below:

Refractory is defined as <30% reduction in spleen length or <10% SVR compared to baseline having received ruxolitinib for ≥12 weeks prior to enrollment, AND on a stable dose for ≥8 weeks prior to starting investigational therapy
Relapsed is defined as an increase in spleen volume of ≥25% by MRI/CT from nadir, or, ≥100% in palpable spleen length from a baseline of 5 to 10 cm BLCM or, ≥50% increase in spleen length from a baseline spleen length ≥10 cm BLCM
Intolerance is defined as the development in patients treated with ruxolitinib for ≥28 days of:
- Red blood cell transfusion requirement of 2 units/month for 2 months
- Grade 3 thrombocytopenia, anemia, hematoma, and/or hemorrhage while on ruxolitinib treatment

Cohort B:

Patients who are JAK inhibitor naïve, AND:
- Require MF-directed treatment, AND
- Have measurable disease burden including one of the following:
  - Disease-related symptoms, determined by a MFSAF or MPN-SAF TSS of ≥10, or at least 2 symptoms with scores ≥3
  - Documented splenomegaly by physical exam, with spleen palpated ≥5 cm below the left costal margin
Both Cohorts A and B:
Willing and able to provide informed consent
Age ≥18 years
Diagnosis of Overt Myelofibrosis (primary, post-ET, or post-PV) per World Health Organization (WHO) diagnostic criteria
Intermediate-1, Intermediate-2, or high-risk disease by Dynamic International Prognostic Scoring System (DIPSS)
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Platelet count ≥100 x 10^9/L prior to dosing on Cycle 1 Day 1
Absolute neutrophil count ≥0.5 x 10^9/L prior to dosing on Cycle 1 Day 1
Peripheral blast count ≤10% prior to dosing on Cycle 1 Day 1
Able to swallow capsules
Women of childbearing potential and fertile men must agree to use an approved method of contraception from Screening until 30 days after the last dose of bomedemstat and ruxolitinib.

Exclusion Criteria:

Those with increased risk of bleeding, including any of the following:
1. Activated partial thromboplastin time (aPTT) ≥1.3 x the local upper limit of normal
2. International normalized ratio (INR) ≥1.3 x the local upper limit of normal
3. Known history of a platelet function disorder
4. Other known bleeding disorder that is active at the time of screening (Von Willebrand's disease, dysfibrinogenemia, hemophilia, etc.)
History of splenectomy or prior splenic irradiation
Use of an investigational agent within 14 days of study treatment (or at least 7 half-lives of that agent, whichever is longer), prior to the first dose of bomedemstat
Current use of monoamine oxidase A and B inhibitors (MAOIs)
Uncontrolled, active infection
Major surgery within 4 weeks of starting the study drug, or not recovered from side effects of surgery
Any other serious medical conditions that could compromise study participation, in the opinion of the investigator
Known HIV infection or known, active hepatitis B or hepatitis C infection
Concurrent second active and non-stable malignancy (patients with a concurrent second active but stable malignancy, i.e., non-melanoma skin cancers, are eligible)
Current use of a prohibited medication (e.g., romiplostim) or expected to require any of these medications during treatment
Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to bomedemstat or LSD1 inhibitors (i.e., monoamine oxidase inhibitors; MAOIs) that contraindicates participation
Evidence at the time of Screening of significant renal or hepatic insufficiency (unless due to hemolysis) as defined by any of the following local lab parameters:
1. Calculated glomerular filtration rate (GFR; using the Cockcroft-Gault equation) <40 mL/min or serum creatinine >1.5 x the local upper limit of normal
2. Aspartate transaminase (AST) or alanine aminotransferase (ALT) ≥2.5 x the local upper limit of normal
Pregnant or lactating females, or females planning to become pregnant at any time during the study
Unwilling or unable to comply with the study protocol

ID	Term
D009196	Myeloproliferative Disorders
D001855	Bone Marrow Diseases
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases