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

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

The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

High-risk Acute Myeloid Leukemia (AML)

• Have a diagnosis of AML according to the World Health Organization (WHO) criteria
• Have an Eastern Cooperative Oncology Group (ECOG) performance status score ≤2
• Have AML that is classified as high risk as defined by one of the following: ≥ 60 years of age who were not candidates for or have refused standard chemotherapy; ≥18 years of age with de novo or secondary AML who were not expected to benefit from standard remission-induction chemotherapy; or had relapsed/refractory AML after no more than 3 previous lines of chemotherapy.

High-risk Myelodysplastic Syndromes (MDS)

• Have a diagnosis of myelodysplastic syndromes according to the World Health Organization (WHO) criteria
• Have either an International Prognostic Scoring System (IPSS) score equivalent to intermediate-2 risk or higher, or a Revised International Prognostic Scoring System (IPSS-R) score equivalent to intermediate risk or higher.
• Have MDS that is classified as high risk as defined by one of the following: participants who have failed first-line therapy; or treatment-related MDS, except if it is associated with favorable cytogenetics, and not a candidate for stem cell transplantation
• Prior autologous stem cell transplant is allowed if a minimum of 3 months has elapsed from the time of transplant and the patient has recovered from transplant-associated toxicities
• Prior allogeneic stem cell transplant is allowed, provided all of the following criteria are met: transplant was >120 days prior to study enrollment; no immunosuppressive medications have been taken for at least 1 month; and no active graft versus host disease (GVHD), excluding Grade 1 skin GVHD
• Has a life expectancy >12 weeks

Exclusion Criteria:

• Is receiving other treatments for the condition (with exceptions and time limits)
• Has had major surgery in last 4 weeks or minor surgery in the last 2 weeks
• Has a scheduled hematopoietic stem-cell transplant
• Is currently using prohibited medications
• Has clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia
• Has a concurrent second active and non-stable malignancy
• Has an uncontrolled active infection
• Has known Human Immunodeficiency Virus (HIV) infection or active Hepatitis B or Hepatitis C virus infection
• Has used an investigational agent within last 14 days
• Is a pregnant or lactating females