Dose Escalation/ Expansion Study of CA-4948 as Monotherapy in Patients With Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndrome (MDS)

Eligibility Criteria

• 1. Males and females ≥18 years of age
• 2. Life expectancy of at least 3 months
• 3. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤1
• 4. Cytomorphology based confirmed diagnosis of MDS or AML (as per World Health Organisation \[WHO\] 2016 classification) with the following characteristics.
• * R/R AMLwith FLT3 mutations who have been previously treated with a FLT3 inhibitor
• * R/R AML with spliceosome mutations of SF3B1 or U2AF1
• * R/R hrMDS (IPSS-R score \> 3.5) with spliceosome mutations of SF3B1 or U2AF1
• * Number of pretreatments: 1 or 2
• 5. Acceptable organ function at screening
• 6. Ability to swallow and retain oral medications
• 7. Negative serum pregnancy test in women of childbearing potential
• 8. Women of childbearing potential and men who partner with a woman of childbearing potential must agree to use highly effective contraceptive methods for the duration of the study and for 90 days after the last dose of emavusertib
• 9. Willing and able to provide written informed consent and comply with the requirements of the trial
• 10. Able to undergo serial bone marrow sampling and peripheral blood sampling
• 1. Diagnosed with acute promyelocytic leukemia (APL, M3)
• 2. Has known active central nervous system (CNS) leukemia
• 3. Allogeneic hematopoietic stem cell transplant (Allo-HSCT) within 60 days of the first dose of emavusertib, or clinically significant graft-versus-host disease (GVHD) requiring ongoing up titration of immunosuppressive medications prior to start of emavusertib
• 4. Chronic myeloid leukemia (CML)
• 5. Any prior systemic anti-cancer treatment such as chemotherapy, immunomodulatory drug therapy, etc., received within 3 weeks (or 5 half-lives) prior to start of emavusertib.
• 6. Use of any investigational agent within 3 weeks or 5 half-lives, whichever is shorter, prior to start of emavusertib
• 7. Presence of an acute or chronic toxicity resulting from prior anti-cancer therapy, with the exception of alopecia that has not resolved to Grade ≤ 1within 7 days prior to start of emavusertib; presence of any acute or chronic non-hematological toxicity ≥ Grade 3 at Screening, or prior to start of emavusertib must resolve to ≤ Grade 2.
• 8. Known allergy or hypersensitivity to any component of the formulation of emavusertib
• 9. Major surgery, other than diagnostic surgery, \<28 days from the start of emavusertib; minor surgery \<14 days from the start of emavusertib
• 10. Patients with active advanced malignant solid tumors
• 11. Known to be human immunodeficiency virus (HIV) positive or have an acquired immunodeficiency syndrome-related illness
• 12. Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) positive or Hepatitis C virus (HCV) infection \<6 months prior to start of emavusertib unless viral load is undetectable, or HCV with cirrhosis
• 13. Uncontrolled or severe cardiovascular disease including myocardial infarction or unstable angina within 6 months prior to CA-4948, New York Heart Association Class II or greater congestive heart failure, or left ventricular ejection fraction \< 40% by echocardiogram or multi-gated acquisition scan, serious arrhythmias uncontrolled on treatment, clinically significant pericardial disease, cardiac amyloidosis, congenital long QT syndrome, or QTc with Fridericia's correction (QTcF) that is unmeasurable or \> 450 milliseconds (msec) on Screening electrocardiogram (ECG)
• 14. Gastrointestinal disease or disorder that could interfere with the swallowing, oral absorption, or tolerance of emavusertib
• 15. Pregnant or lactating
• 16. Systemic fungal, bacterial, viral, or other infection that is not controlled
• 17. Any other severe, acute, or chronic medical, psychiatric or social condition, or laboratory abnormality that may increase the risk of trial participation or emavusertib administration