Bomedemstat (IMG-7289) Plus Ruxolitinib for Myelofibrosis

Phase 2 Study to Assess the Safety and Efficacy of Bomedemstat (IMG-7289) in Combination With Ruxolitinib in Patients With Myelofibrosis

This is an open-label, Phase 2 study of bomedemstat (IMG-7289), an inhibitor of lysine-specific demethylase 1 (LSD1), in combination with JAK inhibition (JAKi) in patients with myelofibrosis.

Study Overview

• Status: Recruiting
• Conditions: Myelofibrosis
• Intervention / Treatment: Drug: Bomedemstat

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Harinder Gill, MD; Phone Number: +852 22554542; Email: gillhsh@hku.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Department of Medicine, the University of Hong Kong, Queen Mary Hospital
    • Contact: Harinder Singh Harry Gill, MD; Phone Number: +852 22554254; Email: gillhsh@hku.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

1. 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:

2. Willing and able to provide informed consent
3. Age ≥18 years
4. Diagnosis of Overt Myelofibrosis (primary, post-ET, or post-PV) per World Health Organization (WHO) diagnostic criteria
5. Intermediate-1, Intermediate-2, or high-risk disease by Dynamic International Prognostic Scoring System (DIPSS)
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
7. Platelet count ≥100 x 10^9/L prior to dosing on Cycle 1 Day 1
8. Absolute neutrophil count ≥0.5 x 10^9/L prior to dosing on Cycle 1 Day 1
9. Peripheral blast count ≤10% prior to dosing on Cycle 1 Day 1
10. Able to swallow capsules
11. 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:

1. 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.)
2. History of splenectomy or prior splenic irradiation
3. 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
4. Current use of monoamine oxidase A and B inhibitors (MAOIs)
5. Uncontrolled, active infection
6. Major surgery within 4 weeks of starting the study drug, or not recovered from side effects of surgery
7. Any other serious medical conditions that could compromise study participation, in the opinion of the investigator
8. Known HIV infection or known, active hepatitis B or hepatitis C infection
9. Concurrent second active and non-stable malignancy (patients with a concurrent second active but stable malignancy, i.e., non-melanoma skin cancers, are eligible)
10. Current use of a prohibited medication (e.g., romiplostim) or expected to require any of these medications during treatment
11. 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

12. 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
13. Pregnant or lactating females, or females planning to become pregnant at any time during the study
14. Unwilling or unable to comply with the study protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A (Patients refractory to, relapsed or intolerant of ruxolitinib): 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; 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.; Other Names: IMG-7289
Experimental: Cohort B (Cohort B will consist of 10 patients who are JAK inhibitor naïve): 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; 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.; Other Names: IMG-7289

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	Proportion of patients who describe a ≥50% reduction in symptom burden by the Myelofibrosis Symptom Assessment Form (MFSAF) by 24 weeks of treatment	24 weeks

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Collaborators: Imago BioSciences,Inc.
• Investigators: Principal Investigator: Harinder Gill, MD, Department of Medicine, the University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: October 3, 2022
• First Submitted That Met QC Criteria: October 3, 2022
• First Posted (Actual): October 6, 2022

Study Record Updates

• Last Update Posted (Actual): May 23, 2023
• Last Update Submitted That Met QC Criteria: May 21, 2023
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Ruxolitinib; Myelofibrosis; Bomedemstat
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Primary Myelofibrosis
• Other Study ID Numbers: IMG-7289-IIS001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes