Primary analysis of a phase II open-label trial of INCB039110, a selective JAK1 inhibitor, in patients with myelofibrosis

John O. Mascarenhas, Moshe Talpaz, Vikas Gupta, Lynda M. Foltz, Michael R. Savona, Ronald L Paquette, A. Robert Turner, Paul Coughlin, Elliott F Winton, Timothy C. Burn, Peter O'Neill, Jason Vt Clark, Deborah S Hunter, Albert Assad, Ronald Hoffman, Srdan Verstovsek

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Combined Janus kinase 1 (JAK1) and JAK2 inhibition therapy effectively reduces splenomegaly and symptom burden related to myelofibrosis but is associated with dose-dependent anemia and thrombocytopenia. In this open-label phase II study, we evaluated the efficacy and safety of three dose levels of INCB039110, a potent and selective oral JAK1 inhibitor, in patients with intermediate- or high-risk myelofibrosis and a platelet count ≥50×109/L. Of 10, 45, and 32 patients enrolled in the 100 mg twice-daily, 200 mg twice-daily, and 600 mg once-daily cohorts, respectively, 50.0%, 64.4%, and 68.8% completed week 24. A ≥50% reduction in total symptom score was achieved by 35.7% and 28.6% of patients in the 200 mg twice-daily cohort and 32.3% and 35.5% in the 600 mg once-daily cohort at week 12 (primary end point) and 24, respectively. By contrast, two patients (20%) in the 100 mg twice-daily cohort had ≥50% total symptom score reduction at weeks 12 and 24. For the 200 mg twice-daily and 600 mg once-daily cohorts, the median spleen volume reductions at week 12 were 14.2% and 17.4%, respectively. Furthermore, 21/39 (53.8%) patients who required red blood cell transfusions during the 12 weeks preceding treatment initiation achieved a ≥50% reduction in the number of red blood cell units transfused during study weeks 1-24. Only one patient discontinued for grade 3 thrombocytopenia. Non-hematologic adverse events were largely grade 1 or 2; the most common was fatigue. Treatment with INCB039110 resulted in clinically meaningful symptom relief, modest spleen volume reduction, and limited myelosuppression.

Original languageEnglish
Pages (from-to)327-335
Number of pages9
JournalHaematologica: the hematology journal
Issue number2
Publication statusPublished - 2017

Cite this

Mascarenhas, J. O., Talpaz, M., Gupta, V., Foltz, L. M., Savona, M. R., Paquette, R. L., Turner, A. R., Coughlin, P., Winton, E. F., Burn, T. C., O'Neill, P., Clark, J. V., Hunter, D. S., Assad, A., Hoffman, R., & Verstovsek, S. (2017). Primary analysis of a phase II open-label trial of INCB039110, a selective JAK1 inhibitor, in patients with myelofibrosis. Haematologica: the hematology journal, 102(2), 327-335.