title: Phase II evaluation of IPI-926, an oral Hedgehog inhibitor, in patients with myelofibrosis.
abstract: The clinical safety and efficacy of IPI-926 was evaluated in 14 patients with myelofibrosis in a phase II study. Patients received 160 mg IPI-926 orally in continuous 28-day cycles. The median treatment duration was 5.1 months, and all patients had discontinued treatment by 7.5 months. Nine patients discontinued due to lack of response as determined by the treating physician, two after developing acute leukemia and one due to disease progression/loss of response. Twelve patients had slight reductions in spleen size (less than 50% from baseline), but symptoms did not improve consistently. One patient achieved transfusion independence lasting 5 months. Reductions in GLI1 mRNA and protein levels, JAK2V617F allele burden, degree of fibrosis or cytokine levels were observed in some patients, but were not significant when evaluated for the cohort. Low-grade gastrointestinal/liver abnormalities were the most common toxicities. The results did not support continued evaluation of IPI-926 as a monotherapy in myelofibrosis.
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center , Houston, TX , USA.
authors: Koji
authors: K
authors: Sasaki
authors: Jason R
authors: JR
authors: Gotlib
authors: Ruben A
authors: RA
authors: Mesa
authors: Kate J
authors: KJ
authors: Newberry
authors: Farhad
authors: F
authors: Ravandi
authors: Jorge E
authors: JE
authors: Cortes
authors: Patrick
authors: P
authors: Kelly
authors: Jeffery L
authors: JL
authors: Kutok
authors: Hagop M
authors: HM
authors: Kantarjian
authors: Srdan
authors: S
authors: Verstovsek
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D055728:Primary Myelofibrosis / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D014704:Veratrum Alkaloids / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; D053823:Hedgehog Proteins; C541444:IPI-926; D014704:Veratrum Alkaloids
keywords: Hedgehog inhibitor; IPI-926; myelofibrosis; saridegib
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