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

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)327-335
Number of pages9
JournalHaematologica: the hematology journal
Volume102
Issue number2
DOIs
Publication statusPublished - 2017

Cite this

Mascarenhas, J. O., Talpaz, M., Gupta, V., Foltz, L. M., Savona, M. R., Paquette, R. L., ... 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. https://doi.org/10.3324/haematol.2016.151126
Mascarenhas, John O. ; Talpaz, Moshe ; Gupta, Vikas ; Foltz, Lynda M. ; Savona, Michael R. ; Paquette, Ronald L ; Turner, A. Robert ; Coughlin, Paul ; Winton, Elliott F ; Burn, Timothy C. ; O'Neill, Peter ; Clark, Jason Vt ; Hunter, Deborah S ; Assad, Albert ; Hoffman, Ronald ; Verstovsek, Srdan. / Primary analysis of a phase II open-label trial of INCB039110, a selective JAK1 inhibitor, in patients with myelofibrosis. In: Haematologica: the hematology journal. 2017 ; Vol. 102, No. 2. pp. 327-335.
@article{63c72f1f702b494f9e4b624ea99499a7,
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.",
author = "Mascarenhas, {John O.} and Moshe Talpaz and Vikas Gupta and Foltz, {Lynda M.} and Savona, {Michael R.} and Paquette, {Ronald L} and Turner, {A. Robert} and Paul Coughlin and Winton, {Elliott F} and Burn, {Timothy C.} and Peter O'Neill and Clark, {Jason Vt} and Hunter, {Deborah S} and Albert Assad and Ronald Hoffman and Srdan Verstovsek",
year = "2017",
doi = "10.3324/haematol.2016.151126",
language = "English",
volume = "102",
pages = "327--335",
journal = "Haematologica: the hematology journal",
issn = "0390-6078",
publisher = "Fondazione Ferrata Storti",
number = "2",

}

Mascarenhas, JO, Talpaz, M, Gupta, V, Foltz, LM, Savona, MR, Paquette, RL, Turner, AR, Coughlin, P, Winton, EF, Burn, TC, O'Neill, P, Clark, JV, Hunter, DS, 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, vol. 102, no. 2, pp. 327-335. https://doi.org/10.3324/haematol.2016.151126

Primary analysis of a phase II open-label trial of INCB039110, a selective JAK1 inhibitor, in patients with myelofibrosis. / Mascarenhas, John O.; Talpaz, Moshe; Gupta, Vikas; Foltz, Lynda M.; Savona, Michael R.; Paquette, Ronald L; Turner, A. Robert; Coughlin, Paul; Winton, Elliott F; Burn, Timothy C.; O'Neill, Peter; Clark, Jason Vt; Hunter, Deborah S; Assad, Albert; Hoffman, Ronald; Verstovsek, Srdan.

In: Haematologica: the hematology journal, Vol. 102, No. 2, 2017, p. 327-335.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Primary analysis of a phase II open-label trial of INCB039110, a selective JAK1 inhibitor, in patients with myelofibrosis

AU - Mascarenhas, John O.

AU - Talpaz, Moshe

AU - Gupta, Vikas

AU - Foltz, Lynda M.

AU - Savona, Michael R.

AU - Paquette, Ronald L

AU - Turner, A. Robert

AU - Coughlin, Paul

AU - Winton, Elliott F

AU - Burn, Timothy C.

AU - O'Neill, Peter

AU - Clark, Jason Vt

AU - Hunter, Deborah S

AU - Assad, Albert

AU - Hoffman, Ronald

AU - Verstovsek, Srdan

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85011592509&partnerID=8YFLogxK

U2 - 10.3324/haematol.2016.151126

DO - 10.3324/haematol.2016.151126

M3 - Article

VL - 102

SP - 327

EP - 335

JO - Haematologica: the hematology journal

JF - Haematologica: the hematology journal

SN - 0390-6078

IS - 2

ER -