Study of REM-422 in Patients with AML or Higher Risk MDS

Eligibility Criteria

• 1. Be able to provide informed consent.
• 2. Be 18 or older at the time of informed consent.
• 3. Disease criteria:
• 1. R/R AML, defined as relapse after transplantation, second or later relapse, refractory to initial induction or reinduction treatment or to initial treatment with hypomethylating (HMA)-based combinations, relapse after initial treatment, or otherwise considered relapsed or refractory in the opinion of the Investigator.
• 2. High-risk and very-high-risk (VHR) MDS (higher-risk) per the International Prognostic Scoring System-Revised (IPSS-R) and/or International Prognostic Scoring System-Molecular (IPSS-M).
• 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 5. Has agreed to undergo serial blood and bone marrow sampling.
• 6. Participants must have completed systemic non-investigational therapy at least 14 days prior to initiating REM-422. Hydroxyurea is permissible for controlling peripheral leukemic blasts prior to enrollment and for up to 28 days following initiation of REM-422.
• 7. Toxicities from prior therapy must be either stable or recovered to ≤ Grade 1.
• 8. Participants must be able to swallow and retain oral medications.
• 9. Oxygen saturation \> 92% on room air or up to 2 L/min supplemental oxygen by nasal cannula with ≤ Grade 1 dyspnea.
• 10. People of childbearing potential (POCBP) must have a negative serum beta-human chorionic gonadotropin test result.
• 11. POCBP must agree to use acceptable, effective methods of contraception and not donate ova from screening until 6 months after discontinuation of REM-422. Women who have undergone surgical or ablative sterilization or who have been postmenopausal for ≥ 2 years are not considered to be of childbearing potential.
• 12. Men must agree to use acceptable, effective methods of contraception and must agree not to donate sperm from the start of receiving REM-422 until 6 months after discontinuation of REM-422.
• 13. Adequate organ function and laboratory parameters
• 1. Active central nervous system (CNS) leukemia or a confirmed diagnosis of CNS leukemia.
• 2. Has undergone hematopoietic stem cell transplantation (HSCT) within 60 days of the first dose of REM-422 or is receiving immunosuppressive therapy post HSCT at the time of screening, or has GVHD requiring systemic treatment (topical steroids for ongoing skin GVHD is permitted).
• 3. Has immediate, life-threatening, severe complications of leukemia, such as uncontrolled bleeding, pneumonia with hypoxia or sepsis, and/or disseminated intravascular coagulation.
• 4. Known hypersensitivity or contraindication to any component of REM-422 or to drugs chemically related to REM-422 or its excipients.
• 5. Clinically significant active infection. Note: Patients with simple urinary tract infection or uncomplicated bacterial pharyngitis responding to active treatment are permitted. Note: Patients receiving intravenous (IV) antibiotics ≤ 7 days prior to enrollment are excluded (prophylactic antibiotics, antivirals, or antifungals are permitted).
• 6. Evidence of active HIV infection.
• 7. Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
• 8. Primary immunodeficiency.
• 9. Current or expected need for daily systemic corticosteroid therapy ≥ 10 mg of prednisone equivalent.
• 10. Live vaccine ≤ 6 weeks prior to the start of REM-422.
• 11. Use of strong CYP3A inhibitors (except azole antifungals) or CYP3A inducers
• 12. Drugs that reduce gastric acidity, such as H2-receptor antagonists (eg, ranitidine, famotidine) and proton pump inhibitors (eg, omeprazole, esomeprazole) within 7 days prior to the initiation of REM-422 administration or during the study.
• 13. Currently pregnant, have intentions to become pregnant during the study duration, or are currently lactating.
• 14. Has dysphagia, short-gut syndrome, gastroparesis, or any other condition that limits the ingestion or gastrointestinal absorption of orally administered drugs.
• 15. Current use of prohibited medication ≤ 1 week before starting REM-422.
• 16. Clinically significant cardiovascular disease:
• 17. Has undergone major surgery (opening a mesenchymal barrier such as the pleural cavity, peritoneum, or meninges or surgical procedures requiring general anesthesia) \< 4 weeks prior to enrollment.
• 18. History of organ transplant that requires use of immunosuppressive agents.
• 19. History or current autoimmune disease requiring systemic treatment (eg, Crohn's disease, ulcerative colitis, rheumatoid arthritis, systemic lupus).
• 20. Radiation therapy ≤ 7 days prior to the start of REM-422.
• 21. Concurrent or previous other malignancy ≤ 2 years of enrollment, except curatively treated malignancies including basal or squamous cell skin cancer, breast cancer, prostate intraepithelial neoplasm, and carcinoma in situ of the cervix.
• 22. Receiving any other investigational treatment for any indication ≤ 3 weeks prior to enrollment.
• 23. Unwillingness or inability to follow protocol requirements.
• 24. Any condition that, in the opinion of the Investigator, would interfere with evaluation of REM-422 or interpretation of the participant's safety or study results.