A phase I, open-label, dose-escalation, multicenter study of the JAK2 inhibitor NS-018 in patients with myelofibrosis

S. Verstovsek, M. Talpaz, E. Ritchie, M. Wadleigh, O. Odenike, C. Jamieson, B. Stein, T. Uno, R. A. Mesa

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

NS-018 is a Janus-activated kinase 2 (JAK2)-selective inhibitor, targeting the JAK–signal transducer and activator of transcription (STAT) pathway that is deregulated in myelofibrosis. In this phase I, dose-escalation portion of a phase I/II study, patients with myelofibrosis received oral NS-018 in continuous 28-day cycles. The primary study objective was to evaluate safety, tolerability and clinically active dose of NS-018. Forty-eight patients were treated; 23 (48%) had previously received a JAK inhibitor (JAKi). The most common drug-related adverse events were thrombocytopenia (27%)/anemia (15%) for hematologic events, and dizziness (23%)/nausea (19%) for non-hematologic events. Once daily NS-018 at 300 mg was chosen as the phase II study dose based on improved tolerability compared with higher doses. A ⩾50% reduction in palpable spleen size was achieved in 56% of patients (47% of patients with prior JAKi treatment), and improvements were observed in myelofibrosis-associated symptoms. Bone marrow fibrosis grade (local assessment) improved from baseline in 11/30 evaluable patients (37%) after 3 cycles of NS-018. JAK2 allele burden was largely unchanged. Changes in cytokine/protein levels were noted after 4 weeks of treatment. NS-018 reached peak plasma concentration in 1–2 h and did not accumulate with multiple dosing. NS-018 will be assessed in patients with previous JAKi exposure in the phase II portion.Leukemia advance online publication, 2 September 2016; doi:10.1038/leu.2016.215.

Original languageEnglish (US)
JournalLeukemia
DOIs
StateAccepted/In press - Sep 2 2016

Fingerprint

Janus Kinase 2
Primary Myelofibrosis
Multicenter Studies
montirelin
Dizziness
Drug-Related Side Effects and Adverse Reactions
Transducers
Thrombocytopenia
Nausea
Publications
Anemia
Leukemia
Spleen
Alleles
Cytokines
Safety
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)
  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Verstovsek, S., Talpaz, M., Ritchie, E., Wadleigh, M., Odenike, O., Jamieson, C., ... Mesa, R. A. (Accepted/In press). A phase I, open-label, dose-escalation, multicenter study of the JAK2 inhibitor NS-018 in patients with myelofibrosis. Leukemia. https://doi.org/10.1038/leu.2016.215

A phase I, open-label, dose-escalation, multicenter study of the JAK2 inhibitor NS-018 in patients with myelofibrosis. / Verstovsek, S.; Talpaz, M.; Ritchie, E.; Wadleigh, M.; Odenike, O.; Jamieson, C.; Stein, B.; Uno, T.; Mesa, R. A.

In: Leukemia, 02.09.2016.

Research output: Contribution to journalArticle

Verstovsek, S, Talpaz, M, Ritchie, E, Wadleigh, M, Odenike, O, Jamieson, C, Stein, B, Uno, T & Mesa, RA 2016, 'A phase I, open-label, dose-escalation, multicenter study of the JAK2 inhibitor NS-018 in patients with myelofibrosis', Leukemia. https://doi.org/10.1038/leu.2016.215
Verstovsek, S. ; Talpaz, M. ; Ritchie, E. ; Wadleigh, M. ; Odenike, O. ; Jamieson, C. ; Stein, B. ; Uno, T. ; Mesa, R. A. / A phase I, open-label, dose-escalation, multicenter study of the JAK2 inhibitor NS-018 in patients with myelofibrosis. In: Leukemia. 2016.
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