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A Phase 1 and 2 study of Filanesib alone and in combination with low-dose dexamethasone in relapsed/refractory
Jatin J Shah1, Jonathan L Kaufman2, Jeffrey A Zonder3
1Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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.
Insights
Filanesib shows manageable safety and encouraging activity in heavily pretreated multiple myeloma patients. This kinesin spindle protein inhibitor demonstrated antimyeloma effects in a Phase 1/2 clinical trial.
Area of Science:
- Oncology
- Pharmacology
Background:
- Filanesib (ARRY-520) is a selective kinesin spindle protein inhibitor.
- Preclinical studies indicated antimyeloma activity for Filanesib.
Purpose of the Study:
- To determine the maximum tolerated dose of Filanesib.
- To evaluate the safety and efficacy of Filanesib in patients with multiple myeloma (MM).
Main Methods:
- An open-label Phase 1/2 study administered Filanesib on Days 1 and 2 of 14-day cycles.
- Patients had received multiple prior therapies, including bortezomib and lenalidomide.
- Expansion cohorts included Filanesib with or without dexamethasone, with prophylactic filgrastim used throughout.
Main Results:
- The most common dose-limiting toxicities were febrile neutropenia and mucosal inflammation.
- Grade 3 and 4 cytopenias occurred in approximately 50% of patients; nonhematologic toxicities were infrequent.
- Phase 2 response rates were 16% for single-agent Filanesib and 15% for Filanesib plus dexamethasone.
Conclusions:
- Filanesib (1.50 mg/m2/day) with prophylactic filgrastim has a manageable safety profile.
- The drug demonstrated encouraging activity in heavily pretreated multiple myeloma patients.
- Low baseline levels of α1-acid glycoprotein may indicate a selective biomarker for response.
