Abstract
7004 Background: Mutations in JAK2 and MPL have been recognized in Philadelphia chromosome-negative myeloproliferative disorders, including PV, ET and PMF, making Janus associated kinase (JAK) a therapeutic target for these diseases. INCB018424 is a potent, selective and orally bioavailable JAK inhibitor with an excellent safety profile supporting its clinical evaluation. Methods: A phase I/II trial of INCB018424 given orally BID is being conducted in patients with PMF and Post-PV/ET MF. Primary end points in this study are responses according to the International Working Group (IWG) consensus criteria for treatment response in myelofibrosis with myeloid metaplasia (IWG-MRT). Results: Overall characteristics of the 32 patients enrolled include median age of 65 yrs; 67% males; 47% PMF, 38% post-PV and 15% post ET; and 87% with JAK2V617F mutation. The starting dose of 25 mg PO BID was demonstrated to be the maximum tolerated dose (MTD) (N = 6 pts). Two patients had grade 4 thrombocytopenia in the 50 mg PO B...
Published Version
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