Shah JJ, et al. – Researchers introduced a Phase 1 and 2 study of Filanesib alone and in combination with low–dose dexamethasone in relapsed/refractory multiple myeloma. For heavily pretreated patients, Filanesib 1.50 mg/m2/day administered with prophylactic filgrastim exhibited a manageable safety profile and encouraging activity.

Methods

• The maximum tolerated dose of Filanesib administered on Days 1 and 2 of 14-Day Cycles in patients with multiple myeloma (MM) was ascertained.
• This open-label Phase 1/2 study included expansion cohorts with and without dexamethasone (40 mg/week).
• Prior bortezomib as well as prior thalidomide and/or lenalidomide were administered to patients in the dose-escalation (N = 31) and Phase 2 single-agent (N = 32) cohorts.
• Furthermore, 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.
• During dose escalation, prophylactic filgrastim was incorporated.
• In addition, it was used throughout Phase 2.

Results

• A median of ≥6 prior therapies was given to patients in each cohort.
• Febrile neutropenia and mucosal inflammation were the most common dose-limiting toxicities.
• Grade 3 and 4 cytopenias were reported in approximately 50% of patients, in Phase 2.
• This study noted the infrequency of nonhematologic toxicities.
• Moreover, Phase 2 response rates (partial responses or better) were 16% (single agent) and 15% (Filanesib plus dexamethasone).
• Data demonstrated low baseline levels of α1-acid glycoprotein, a potential selective biomarker in all responding patients.