title: Primary analysis of a phase II open-label trial of INCB039110, a selective JAK1 inhibitor, in patients with myelofibrosis.
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.
authors: The Icahn School of Medicine at Mount Sinai, New York, NY, USA john.mascarenhas@mssm.edu.
authors: John O
authors: JO
authors: Mascarenhas
authors: University of Michigan Cancer Center, Ann Arbor, MI, USA.
authors: Moshe
authors: M
authors: Talpaz
authors: Princess Margaret Cancer Centre, Toronto, ON, Canada.
authors: Vikas
authors: V
authors: Gupta
authors: St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada.
authors: Lynda M
authors: LM
authors: Foltz
authors: Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
authors: Michael R
authors: MR
authors: Savona
authors: University of California, Los Angeles, CA, USA.
authors: Ronald
authors: R
authors: Paquette
authors: Cross Cancer Institute Edmonton, AB, Canada.
authors: A Robert
authors: AR
authors: Turner
authors: Monash University, VIC, Australia.
authors: Paul
authors: P
authors: Coughlin
authors: Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors: Elliott
authors: E
authors: Winton
authors: Incyte Corporation, Wilmington, DE, USA.
authors: Timothy C
authors: TC
authors: Burn
authors: Incyte Corporation, Wilmington, DE, USA.
authors: Peter
authors: P
authors: O'Neill
authors: Incyte Corporation, Wilmington, DE, USA.
authors: Jason
authors: J
authors: Clark
authors: Incyte Corporation, Wilmington, DE, USA.
authors: Deborah
authors: D
authors: Hunter
authors: Incyte Corporation, Wilmington, DE, USA.
authors: Albert
authors: A
authors: Assad
authors: The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors: Ronald
authors: R
authors: Hoffman
authors: The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Srdan
authors: S
authors: Verstovsek
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001384:Azetidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007539:Isonicotinic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D055728:Primary Myelofibrosis / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D001384:Azetidines; D016207:Cytokines; C000603457:INCB039110; D007539:Isonicotinic Acids; D047428:Protein Kinase Inhibitors; D053613:Janus Kinase 1