Novel Kinesin Spindle Protein Inhibitor Filanesib Plus Carfilzomib in Patients with Relapsed and/or Refractory Multiple Myeloma (RRMM)
Filanesib (ARRY-520), a kinesin spindle protein inhibitor, has demonstrated promising clinical activity in patients with multiple myeloma (MM) refractory to proteasome inhibitors (PIs) and immunomodulatory drugs.1 Carfilzomib is an irreversible PI indicated for the treatment of patients with relapsed/refractory MM (RRMM) as a single agent and in combination with lenalidomide/dexamethasone for the treatment of patients with relapsed MM. In a 2-part phase 1b study conducted to determine the maximum tolerated dose and the safety/tolerability of carfilzomib plus filanesib in RRMM, part A of the study demonstrated the safety of fixed-dose carfilzomib (approved dose and schedule) plus filanesib 1.5 mg/m2.2 At the ASH 2015 meeting, Shah and colleagues reported on preliminary results of this study following subsequent enrollment in the part A dose-expansion cohort and part B of the trial (with fixed-dose filanesib and dose escalation of carfilzomib to 56 mg/m2).3
A total of 58 patients were enrolled in the study; eligible patients were transplant-ineligible, refractory/intolerant to bortezomib, and had prior lenalidomide exposure. Of these, 20 patients were enrolled in the part A dose-escalation phase, 14 carfilzomib-naïve patients in part A dose expansion, 11 carfilzomib-refractory patients in part A dose expansion, and 13 patients in the part B dose-escalation phase. In the part A carfilzomib-naïve cohort (n=34), an overall response rate (ORR, ?partial response) of 44% was achieved. The median progression-free survival (PFS) of the carfilzomib-naive cohort was 12.9 months, and the median overall survival (OS) was not reached at a median follow-up time of 24 months. No carfilzomib-refractory patient (n=11) in the part A cohort achieved a response. In the part B dose-escalation phase of 13 patients, 4 patients achieved a response. No dose-limiting toxicities were observed in the 3 cohorts. The predominant grade 3/4 adverse events (AEs) experienced by patients were hematologic, including anemia, thrombocytopenia, and neutropenia, all of which were transient and manageable. Growth factor support was used in all patients. Grade 3/4 nonhematologic AEs included lung infection; fatigue; elevated creatinine; myalgia and elevated serum lipase; dyspnea; and sinusitis. Treatment- emergent serious AEs included lung infection, renal dysfunction, febrile neutropenia, heart failure, bacteremia, lethargy, sinusitis, and diarrhea. Based on these results, the authors concluded that filanesib in combination with carfilzomib may represent a promising steroid-sparing regimen in patients with relapsed/refractory MM.
- Shah JJ, et al. ASH 2013. Abstract 1982.
- Lonial S, et al. ASCO 2015. Abstract TPS8613.
- Shah JJ, et al. ASH 2015. Abstract 376.