Perlmutter Cancer Center

Study ASTX030-01 is being conducted in subjects with myelodysplastic syndromes (MDS), MDS/myeloproliferative neoplasms (MPN) including chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML) who are candidates to receive treatment with single agent azacitidine based on local country approvals and/or local institutional standard practice. Study ASTX030-01 is designed to move efficiently from Phase 1 to Phase 3. • Phase 1 is an open-label Dose Escalation Stage (Stage A) followed by a Dose Expansion Stage (Stage B) of oral ASTX030 (cedazuridine in combination with azacitidine). Multiple doses/formulations will be evaluated. New formulations will generally be investigated in Phase 1 Stage A. Approximately 54 (Stage A) and 24-64 (Stage B) subjects will be treated in Phase 1. As of Amendment 1, an assessment of food effect (12 subjects) on the PK of ASTX030 was implemented for Phase 1 Stage B and is described below and in Section 5.3.1. As of Amendment 2, each additional dose level/formulation selected by the DSRC for evaluation in Phase 1 Stage B will be evaluated in approximately 12-24 additional subjects or as determined by the DSRC (ie, if emerging data indicates that this dose level/formulation does not achieve parity with SC azacitidine, fewer subjects may be evaluated). • Phase 2 is a randomized open-label crossover study comparing oral ASTX030 to SC azacitidine administered using the once daily × 7 days dosing schedule for each 28-day cycle as detailed in Section 1.3.1. It is expected that up to approximately 60 subjects will be treated at the RP2D depending on the number of doses/formulations tested in Phase 2. • Phase 3 is a randomized open-label crossover study comparing oral ASTX030 FDC tablet(s) to SC azacitidine administered using the once daily × 7 days dosing schedule for each 28-day cycle as detailed in Section 1.3.1. Depending on the intrapatient variability observed during Phase 2, it is expected that between approximately 75 and 115 subjects will be randomized in Phase 3. This study is designed to assess the safety and tolerability, pharmacokinetics, and clinical activity of ASTX030 and identify an oral dose combination of ASTX030 that yields azacitidine systemic exposure that approximates parity to that of SC azacitidine alone (based on total cycle azacitidine AUC0-24).