The objective of this study is to establish the efficacy, safety, and tolerability of S243249 and to establish the recommended phase 2 dose (RP2D) of S243249 monotherapy in participants with relapsed/refractory (R/R) acute leukemia with select mutations. Phase 1 dose optimization will determine the RP2D to be used in Phase 2 dose expansion. The study will include a screening period, a treatment period consisting of continuous 28-day cycles of treatment, a safety follow-up period and a long-term follow-up period. Participants may undergo blood tests, electrocardiogram (ECG), bone marrow aspirations, vital sign checks, questionnaires, and physical exams.
Aged ≥ 18 years old.
Negative serum pregnancy (β-hCG) test in women of childbearing potential at screening
Primary refractory disease, defined as non-response to 2 courses of standard induction therapy.
R/R disease, defined as > 5% blasts on bone marrow aspirate (BMA) / bone marrow biopsy (BMB) after completing prior therapy.
Active central nervous system (CNS) leukemia (including imaging abnormalities and cerebrospinal fluid (CSF) smear or flow cytometry indicating leukemia cells)).
Active disseminated intravascular coagulation (DIC).
Active uncontrolled infection (prophylaxis because of absolute neutrophil count [ANC] is excepted).
Diagnosis of acute promyelocytic leukemia (APL, M3).