Phase 2 study of gandotinib (LY2784544) in patients with myeloproliferative neoplasms

J. Berdeja, F. Palandri, M. R. Baer, D. Quick, J. J. Kiladjian, G. Martinelli, Amit K. Verma, O. Hamid, R. Walgren, C. Pitou, P. L. Li, A. T. Gerds

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: The Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are associated with increases in janus kinase 2 (JAK2) signaling, often resulting from the JAK2 V617F mutation. LY2784544 (gandotinib) is a potent, selective, small-molecule inhibitor of JAK2 that has potential dose-dependent selectivity for the JAK2 V617F mutation and may inhibit additional JAK2 mutant isoforms in nonclinical testing. Methods: A multicenter, single-arm, outpatient phase 2 study evaluated the efficacy, safety, and pharmacokinetics (PK) of gandotinib administered to patients (120 mg once daily) with MPNs, including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF). Between May 2012 and March 2015, 138 patients received at least one dose of study drug. Findings: Most frequent Grade 3 or 4 treatment-emergent adverse events that were considered study-drug related were anemia (11.6%), hyperuricemia (3.2%), fatigue (2.9%), diarrhea (2.2%), and thrombocytopenia (2.2%). Overall response rates (ORRs) in patients with JAK2 V617F-mutated PV, ET, and MF were 95%, 90.5%, and 9.1%, respectively, while patients with ET and MF without the JAK2 V617F mutations had ORRs of 43.7% and 0%, respectively. Interpretations: LY2784544 demonstrated efficacy in JAK2 V617F-mutated MPNs, including in patients previously on ruxolitinib therapy, who had an ORR of 3.3%. At the 1-year visit, 44% of patients experienced a ≥50% improvement in the MPN-Symptom Assessment Form Total Symptom Score, and 26% of patients had a 50% reduction in Brief Fatigue Inventory score.

Original languageEnglish (US)
Pages (from-to)82-88
Number of pages7
JournalLeukemia Research
Volume71
DOIs
StatePublished - Aug 1 2018

Fingerprint

LY2784544
Janus Kinase 2
Essential Thrombocythemia
Primary Myelofibrosis
Neoplasms
Polycythemia Vera
Mutation
Fatigue
Philadelphia Chromosome
Hyperuricemia
Symptom Assessment
Thrombocytopenia
Pharmaceutical Preparations

Keywords

  • Gandotinib
  • JAK2
  • LY2784544
  • MPN

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Berdeja, J., Palandri, F., Baer, M. R., Quick, D., Kiladjian, J. J., Martinelli, G., ... Gerds, A. T. (2018). Phase 2 study of gandotinib (LY2784544) in patients with myeloproliferative neoplasms. Leukemia Research, 71, 82-88. https://doi.org/10.1016/j.leukres.2018.06.014

Phase 2 study of gandotinib (LY2784544) in patients with myeloproliferative neoplasms. / Berdeja, J.; Palandri, F.; Baer, M. R.; Quick, D.; Kiladjian, J. J.; Martinelli, G.; Verma, Amit K.; Hamid, O.; Walgren, R.; Pitou, C.; Li, P. L.; Gerds, A. T.

In: Leukemia Research, Vol. 71, 01.08.2018, p. 82-88.

Research output: Contribution to journalArticle

Berdeja, J, Palandri, F, Baer, MR, Quick, D, Kiladjian, JJ, Martinelli, G, Verma, AK, Hamid, O, Walgren, R, Pitou, C, Li, PL & Gerds, AT 2018, 'Phase 2 study of gandotinib (LY2784544) in patients with myeloproliferative neoplasms', Leukemia Research, vol. 71, pp. 82-88. https://doi.org/10.1016/j.leukres.2018.06.014
Berdeja J, Palandri F, Baer MR, Quick D, Kiladjian JJ, Martinelli G et al. Phase 2 study of gandotinib (LY2784544) in patients with myeloproliferative neoplasms. Leukemia Research. 2018 Aug 1;71:82-88. https://doi.org/10.1016/j.leukres.2018.06.014
Berdeja, J. ; Palandri, F. ; Baer, M. R. ; Quick, D. ; Kiladjian, J. J. ; Martinelli, G. ; Verma, Amit K. ; Hamid, O. ; Walgren, R. ; Pitou, C. ; Li, P. L. ; Gerds, A. T. / Phase 2 study of gandotinib (LY2784544) in patients with myeloproliferative neoplasms. In: Leukemia Research. 2018 ; Vol. 71. pp. 82-88.
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abstract = "Background: The Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are associated with increases in janus kinase 2 (JAK2) signaling, often resulting from the JAK2 V617F mutation. LY2784544 (gandotinib) is a potent, selective, small-molecule inhibitor of JAK2 that has potential dose-dependent selectivity for the JAK2 V617F mutation and may inhibit additional JAK2 mutant isoforms in nonclinical testing. Methods: A multicenter, single-arm, outpatient phase 2 study evaluated the efficacy, safety, and pharmacokinetics (PK) of gandotinib administered to patients (120 mg once daily) with MPNs, including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF). Between May 2012 and March 2015, 138 patients received at least one dose of study drug. Findings: Most frequent Grade 3 or 4 treatment-emergent adverse events that were considered study-drug related were anemia (11.6{\%}), hyperuricemia (3.2{\%}), fatigue (2.9{\%}), diarrhea (2.2{\%}), and thrombocytopenia (2.2{\%}). Overall response rates (ORRs) in patients with JAK2 V617F-mutated PV, ET, and MF were 95{\%}, 90.5{\%}, and 9.1{\%}, respectively, while patients with ET and MF without the JAK2 V617F mutations had ORRs of 43.7{\%} and 0{\%}, respectively. Interpretations: LY2784544 demonstrated efficacy in JAK2 V617F-mutated MPNs, including in patients previously on ruxolitinib therapy, who had an ORR of 3.3{\%}. At the 1-year visit, 44{\%} of patients experienced a ≥50{\%} improvement in the MPN-Symptom Assessment Form Total Symptom Score, and 26{\%} of patients had a 50{\%} reduction in Brief Fatigue Inventory score.",
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AU - Palandri, F.

AU - Baer, M. R.

AU - Quick, D.

AU - Kiladjian, J. J.

AU - Martinelli, G.

AU - Verma, Amit K.

AU - Hamid, O.

AU - Walgren, R.

AU - Pitou, C.

AU - Li, P. L.

AU - Gerds, A. T.

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