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|Ref Type||Journal Article|
|Authors||Shah JJ, Kaufman JL, Zonder JA, Cohen AD, Bensinger WI, Hilder BW, Rush SA, Walker DH, Tunquist BJ, Litwiler KS, Ptaszynski M, Orlowski RZ, Lonial S|
|Title||A Phase 1 and 2 study of Filanesib alone and in combination with low-dose dexamethasone in relapsed/refractory multiple myeloma.|
|Date||2017 Dec 01|
|Abstract Text||Filanesib (ARRY-520) is a highly selective inhibitor of kinesin spindle protein, which has demonstrated preclinical antimyeloma activity.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.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.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.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Filanesib||ARRY-520||Filanesib (ARRY-520) inhibits Kinesin Spindle Protein (KSP), which may result in mitotic arrest and apoptosis of tumor cells (PMID: 28817190, PMID: 19458629).|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||multiple myeloma||not applicable||Dexamethasone + Filanesib||Phase Ib/II||Actionable||In a Phase I/II trial, treatment with the combination of Filansenib (ARRY-520) and dexamethasone in a Phase II cohort resulted in an overall response rate of 15% (8/54), clinical benefit rate of 20% (11/54), and median overall survival of 10.7 months in patients with refractory or relapsed multiple myeloma (PMID: 28817190, NCT00821249).||28817190|
|Unknown unknown||multiple myeloma||not applicable||Filanesib||Phase Ib/II||Actionable||In a Phase I/II trial, treatment with Filansenib (ARRY-520) demonstrated safety, and resulted in an overall response rate of 16% (5/31), clinical benefit rate of 23% (7/31), and median overall survival of 19.0 months in the Phase II portion in patients with refractory or relapsed multiple myeloma (PMID: 28817190, NCT00821249).||28817190|