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

  • Haematologica. 2017 Feb;102(2):327-335. doi: 10.3324/haematol.2016.151126.
John O Mascarenhas  1 ,  Moshe Talpaz  2 ,  Vikas Gupta  3 ,  Lynda M Foltz  4 ,  Michael R Savona  5 ,  Ronald Paquette  6 ,  A Robert Turner  7 ,  Paul Coughlin  8 ,  Elliott Winton  9 ,  Timothy C Burn  10 ,  Peter O'Neill  10 ,  Jason Clark  10 ,  Deborah Hunter  10 ,  Albert Assad  10 ,  Ronald Hoffman  11 ,  Srdan Verstovsek  12
Affiliations
  • 1. The Icahn School of Medicine at Mount Sinai, New York, NY, USA [email protected].
  • 2. University of Michigan Cancer Center, Ann Arbor, MI, USA.
  • 3. Princess Margaret Cancer Centre, Toronto, ON, Canada.
  • 4. St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.
  • 5. Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
  • 6. University of California, Los Angeles, CA, USA.
  • 7. Cross Cancer Institute Edmonton, AB, Canada.
  • 8. Monash University, VIC, Australia.
  • 9. Winship Cancer Institute, Emory University, Atlanta, GA, USA.
  • 10. Incyte Corporation, Wilmington, DE, USA.
  • 11. The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 12. The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
PMID: 27789678 DOI: 10.3324/haematol.2016.151126
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 ≥50×109/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.

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