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Clin Cancer Res. 2015 Apr 15;21(8):1843-50. doi: 10.1158/1078-0432.CCR-14-1845. Epub 2015 Jan 27.

An Open-Label, Multicenter, Phase I/II Study of JNJ-40346527, a CSF-1R Inhibitor, in Patients with Relapsed or Refractory Hodgkin Lymphoma.

Author information

1
University Hospital of Cologne, Department I of Internal Medicine, Cologne, Germany. bastian.von-tresckow@uk-koeln.de.
2
Centre Hospitalier Régional Universitaire (CHRU) de Lille, Lille, France.
3
Institut Gustave Roussy, Villejuif, France.
4
University Hospital of Wurzburg, Medical Clinic and Polyclinic II, Wurzburg, Germany.
5
Janssen Research and Development, LLC., Raritan, New Jersey.
6
Janssen Research and Development, LLC., Spring House, Pennsylvania.
7
Janssen Biologics B.V., Leiden, the Netherlands.
8
University Hospital of Cologne, Department I of Internal Medicine, Cologne, Germany.

Abstract

PURPOSE:

This phase I/II study investigated JNJ-40346527, a selective inhibitor of the colony-stimulating factor-1 receptor (CSF-1R) tyrosine kinase as treatment for relapsed or refractory classical Hodgkin lymphoma (cHL).

EXPERIMENTAL DESIGN:

Patients ≥18 years with histopathologically confirmed initial diagnosis of cHL that had relapsed or was refractory after ≥1 appropriate therapies were assigned to sequential cohorts of oral daily doses of JNJ-40346527 (150, 300, 450, 600 mg every day, and 150 mg twice a day). For the dose-escalation phase, the primary endpoint was to establish the recommended phase II dose. Secondary endpoints included safety, pharmacokinetics, and pharmacodynamics.

RESULTS:

Twenty-one patients [(150 mg: 3; 300 mg: 5; 450 mg: 3, 600 mg: 3) every day, and 150 mg twice a day: 7] were enrolled, 10 men, median age 40 (range, 19-75) years, median number of prior systemic therapies 6 (range, 3-14). No dose-limiting toxicities were observed; maximum-tolerated dose was not established. Best overall response was complete remission in 1 patient (duration, +352 days) and stable disease in 11 patients: (duration, 1.5-8 months). Median number of cycles: 4 (range, 1-16). Most common (≥20% patients) possibly drug-related adverse events (per investigator assessment) were nausea (n = 6), headache, and pyrexia (n = 5 each). JNJ-40346527 exposure increased in near dose-proportional manner over a dose range of 150 to 450 mg every day, but plateaued at 600 mg every day. Target engagement was confirmed (>80% inhibition of CSF-1R phosphorylation, 4 hours after dosing).

CONCLUSIONS:

JNJ-40346527, a selective inhibitor of CSF-1R was well tolerated, and preliminary antitumor results suggested limited activity in monotherapy for the treatment of cHL.

PMID:
25628399
DOI:
10.1158/1078-0432.CCR-14-1845
[Indexed for MEDLINE]
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