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

• Authors: John O. Mascarenhas, The Icahn School of Medicine at Mount Sinai; Moshe Talpaz, University of Michigan Cancer Center; Vikas Gupta, Princess Margaret Cancer Centre; Lynda M. Foltz, University of British Columbia; Michael R. Savona, Vanderbilt University Medical Center; Ronald Paquette, University of California; A. Robert Turner, Cross Cancer Institute Edmonton; Paul Coughlin, Monash University; Elliott Winton, Emory University; Timothy C. Burn, Incyte Corporation; Peter O'Neill, Incyte Corporation; Jason Clark, Incyte Corporation; Deborah Hunter, Incyte Corporation; Albert Assad, Incyte Corporation; Ronald Hoffman, The Icahn School of Medicine; Srdan Verstovsek, The University of Texas MD Anderson Cancer Center
• Journal Title: Haematologica
• Volume: Volume 102, Number 2
• Publisher: Ferrata Storti Foundation | 2017-02, Pages 327-335
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.3324/haematol.2016.151126
• Subjects: Health Sciences, General; Health Sciences, Oncology
• Keywords: myelofibrosis; JAK1 inhibitor; INCB039110; bone marrow fibrosis

Abstract

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 ≥50×10(9)/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.