Pharmion reports combination therapy effective against MDS and AML

A 53% response rate was demonstrated at the 90mg dose with a median time to response of less than two months. The overall results indicate a 36% response rate for patients evaluated at all doses in this Phase I/II study.

Patients with myelodysplastic syndrome (MDS), relapsed/refractory acute myelogenous leukemia (AML), or untreated patients with AML were given Vidaza at its approved dose/schedule (75 mg/m2 SC daily for the first 7 days of a 28 day cycle). MGCD0103 was added orally three-times a week starting on the fifth day of Vidaza administration.

Of the 52 evaluable patients treated at all dose levels in the study (43 patients with AML and 9 with MDS), 36% (19 patients) demonstrated objective responses to the combined treatment (eight complete responses [CR], ten complete responses with incomplete peripheral count recovery [CRi], and one partial response [PR]). Among the 19 patients receiving MGCD0103 at a dose of 90mg, 10 (53%) achieved a response. Of the 52 evaluable patients, 71% had received prior therapy. Of particular note, in an overall survival analysis, patients with a response had a 66% reduction in the risk of death when compared to non-responders.

The recommended Phase II dose for MGCD0103 was determined to be 90mg. Vidaza did not affect MGCD0103 pharmacokinetics, nor did co-administration of MGCD0103 impact the pharmacokinetics of Vidaza. A majority of patients exhibited a substantial reduction in PBMC HDAC activity during treatment with the combination.

Donald Corcoran, president and CEO of MethylGene, said: “The results of this study provide the basis for our planned three-arm randomized study of MGCD0103 and Vidaza in AML and MDS patients.”