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

摘要

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/m 2 /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 .