The AfFIRM Study: A multicenter phase 2 study of single-agent filanesib (ARRY-520) in patients with advanced multiple myeloma.

TPS8613 Background: An unmet medical need exists for patients (pts) with multiple myeloma (MM) whose disease has progressed despite prior exposure to immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs), particularly if their disease has become refractory to carfilzomib (CFZ) and/or pomalidomide (POM). Filanesib is a highly selective, targeted kinesin spindle protein (KSP) inhibitor that has shown promising activity and a manageable safety profile as a single agent in heavily pretreated pts with MM. Due to a distinct mechanism of action, filanesib is expected to be active in cells that have become resistant to IMiDs and PIs, potentially addressing a significant unmet need in the treatment of patients with refractory MM. Nonclinical and prior clinical data have suggested that pts with high serum levels of α 1-acid glycoprotein (AAG) may not obtain therapeutic benefit from filanesib as a result of decreased unbound fraction of drug and ineffective therapeutic exposure. The correlation between Baseline AAG and clinical response to single-agent filanesib will be evaluated. Methods: This single-arm Phase 2 study is designed to assess the efficacy and safety of single-agent filanesib in ~160 pts with MM at centers in North America and Europe (NCT02092922). Eligible pts have received at least 2 prior lines of therapy; have received prior bortezomib and lenalidomide; and have disease refractory to CFZ and/or POM. Filanesib (1.50 mg/m2/day) is administered intravenously on Days 1, 2, 15 and 16 in continuous 28-day cycles with prophylactic filgrastim until disease progression or unacceptable toxicity. Objective response is assessed by independent central review and classified per International Myeloma Working Group (IMWG) criteria. AAG is measured by a central laboratory using a validated immunoturbidimetric assay. The primary endpoint is objective response rate (ORR) in pts with low Baseline AAG. Secondary endpoints are ORR in pts with high Baseline AAG, duration of response, time to best response, clinical benefit rate, disease control rate, progression-free survival, time to next treatment, overall survival and safety. The study includes a 25-pt pharmacokinetics/QT substudy. Clinical trial information: NCT02092922.