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Cancer. 2017 Dec 1;123(23):4617-4630. doi: 10.1002/cncr.30892. Epub 2017 Aug 17.

A Phase 1 and 2 study of Filanesib alone and in combination with low-dose dexamethasone in relapsed/refractory multiple myeloma.

Author information

1
Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas.
2
Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia.
3
Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.
4
Fox Chase Cancer Center, Philadelphia, Pennsylvania.
5
Fred Hutchinson Cancer Research Center, Seattle, Washington.
6
Array BioPharma, Inc, Boulder, Colorado.

Abstract

BACKGROUND:

Filanesib (ARRY-520) is a highly selective inhibitor of kinesin spindle protein, which has demonstrated preclinical antimyeloma activity.

METHODS:

This open-label Phase 1/2 study determined the maximum tolerated dose of Filanesib administered on Days 1 and 2 of 14-Day Cycles in patients with multiple myeloma (MM) and included expansion cohorts with and without dexamethasone (40 mg/week). Patients in the dose-escalation (N = 31) and Phase 2 single-agent (N = 32) cohorts had received prior bortezomib as well as prior thalidomide and/or lenalidomide. Patients in the Phase 2 Filanesib plus dexamethasone cohort (N = 55) had received prior alkylator therapy and had disease refractory to lenalidomide, bortezomib, and dexamethasone. Prophylactic filgrastim was incorporated during dose escalation and was used throughout Phase 2.

RESULTS:

Patients in each cohort had received a median of ≥6 prior therapies. The most common dose-limiting toxicities were febrile neutropenia and mucosal inflammation. In Phase 2, Grade 3 and 4 cytopenias were reported in approximately 50% of patients. Nonhematologic toxicities were infrequent. Phase 2 response rates (partial responses or better) were 16% (single agent) and 15% (Filanesib plus dexamethasone). All responding patients had low baseline levels of α1-acid glycoprotein, a potential selective biomarker.

CONCLUSIONS:

Filanesib 1.50 mg/m2 /day administered with prophylactic filgrastim has a manageable safety profile and encouraging activity in heavily pretreated patients This study is registered at www.clinicaltrials.gov as NCT00821249. Cancer 2017;123:4617-4630. © 2017 American Cancer Society.

KEYWORDS:

dexamethasone; filanesib. kinesin; maximum tolerated dose; multiple myeloma; pharmacokinetics; spindle poles

PMID:
28817190
PMCID:
PMC5856158
[Available on 2018-12-01]
DOI:
10.1002/cncr.30892
[Indexed for MEDLINE]

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