2017 EHA: DOSE-CONFIRMATION STUDY OF ORAL ASTX727, A COMBINATION OF ORAL DECITABINE WITH A CYTIDINE DEAMINASE INHIBITOR (CDAI) E7727, IN SUBJECTS WITH MYELODYSPLASTIC SYNDROMES (MDS): PRELIMINARY RESULTS

Summary
An oral hypomethylatingagent which could be administered in a dose which would emulate parenteral pharmacokinetics would be more convenient and potentially enhance adherence to treatment. Heretofore, rapid clearance by cytidine deaminase (CDA) during first pass has prevented oral administration.1E7727, a novel CDAi, is orally bioavailable with a large safety margin and reproducible effectiveness in preclinical models.2A phase I dose finding study found that a fixed oral combination of 35 mg of decitabine and 100 mg of E7727 (ASTX727) should produce similar pharmacokinetics (PK) to decitabineadministered intravenously at 20 mg/m2 as a 1-hour infusion (DAC IV).3We tested this hypothesis in a randomized cross-over study of DAC IV vs ASTX727 and report the preliminary results here.

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ASTX727_Poster_EHA_abst-E1192_Garcia-Manero_final.pdf