ASCERTAIN phase III study of ASTX 727 meets primary endpoint in myelodysplastic syndromes or chronic myelomonocytic leukemia

Astex Pharmaceuticals announced top-line results from the ASCERTAIN phase III study evaluating ASTX 727 (cedazuridine and decitabine) fixed-dose combination vs decitabine IV in adults with intermediate and high-risk Myelodysplastic Syndromes (MDS) or Chronic Myelomonocytic Leukemia (CMML). The study met its primary endpoint of decitabine exposure equivalence of 5-day dosing between orally administered ASTX 727 and IV decitabine as per the protocol analysis plan.

Safety and clinical activity were similar to that observed in a previous phase I/II study. The study confirmed the safety profile and clinical activity of the cedazuridine and decitabine fixed-dose combination and showed it was similar to the expected clinical profile of decitabine. The full data will be presented at an upcoming scientific meeting. Astex plans to file an NDA with the US FDA by the end of 2019.

Comment: ASTX 727 has been evaluated in a phase I/II pharmacokinetics-guided dose escalation and dose confirmation study in patients with MDS and CMML to define appropriate doses of the individual components of ASTX 727 so that decitabine exposure after oral administration is similar to exposure after IV decitabine at the approved daily dose of a 1-hour infusion at 20 mg/m2. This study demonstrated that ASTX 727 allowed decitabine to be delivered orally at a dose that emulates parenteral pharmacokinetics, as measured by 5-day area-under-the-curve (AUC). The drug’s safety profile was similar to that of IV decitabine. Of particular note was the low level of gastrointestinal adverse events.