Myelodysplastic Syndrome Acute Myeloid Leukemia

The objective of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of S241656 and to determine the recommended dose for expansion (RDE) of S241656 in participants with relapsed/refractory (R/R) acute myeloid leukemia (AML), myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), or chronic myelomonocytic leukemia (CMML). Part 1A dose escalation will determine the RDE to be used in a future expansion stage of the trial. An optional Part 1B drug-drug interaction (DDI) substudy will evaluate the effect of posaconazole on the PK of S241656. The study consists of a screening period of up to 21 days, a treatment period consisting of continuous 28-day cycles of treatment, an end-of-treatment visit, a safety follow-up period, and long-term disease and survival follow-up every 3 months. Participants in the optional DDI substudy may continue treatment in the main study following completion of the DDI assessment period. Participants may undergo bone marrow aspirates and/or biopsies, blood tests, electrocardiograms (ECGs), echocardiograms or multigated acquisition (MUGA) scans, physical examinations, ophthalmologic assessments, and disease response questionnaires.

This is an open-label, Phase 1 study to determine the safety, tolerability, and efficacy of APL-4098 alone, and in combination with azacitidine, and in combination with azacitidine plus venetoclax for the treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS)/AML and MDS-excess blasts (EB).

The primary objective is to define the safety and tolerability of AB8939 in patients with AML by determining the dose-limiting toxicities, the maximum tolerated dose, and the recommended dose for dose expansion study.