Filanesib (ARRY-520) is a first-in-class kinesin spindle protein (KSP) inhibitor that is being evaluated in combination with the proteasome inhibitor carfilzomib versus carfilzomib alone in an ongoing, randomized, open-label phase 2 study in patients with relapsed and/or refractory multiple myeloma (RRMM); Zonder and colleagues presented preliminary results of this trial.1 A total of 77 patients who were carfilzomib-naïve, had received at least 2 prior regimens, including bortezomib and an immunomodulatory drug (IMiD), and were refractory to the last regimen were enrolled in the trial. Patients were randomized 2:1 to receive either carfilzomib (20/27 mg/m2 intravenously [IV]) plus filasenib (1.25 mg/m2 IV) (arm A; n = 52) or carfilzomib alone (arm B; n = 25); of these, 50 patients were evaluable for this analysis. Of the patients in arm A, 47% had high-risk cytogenetics compared with 44% in arm B. In addition, 60% of the patients in both arms were dual-refractory to an IMiD and bortezomib.
In this heavily pretreated patient population (median prior regimens 4-5 for the 2 arms), carfilzomib/filanesib treatment resulted in an increased median progression-free survival (PFS) of 8.5 months versus 3.7 months for carfilzomib alone. The overall response rate (ORR) was 28%, including 3 very good partial responses and 9 partial responses, compared with an ORR of 12% with carfilzomib alone. Notably, the patient subset with double-refractory disease to IMiDs and bortezomib achieved an ORR of 33% with both carfilzomib/filanesib and carfilzomib alone. Low levels of alpha-1-acid glycoprotein (AAG) was associated with higher ORR and PFS rates in both arms.
Grade 3/4 hematologic laboratory abnormalities were higher with carfilzomib/filanesib therapy and included neutropenia (26% vs 12%) and thrombocytopenia (31% vs 12%). Dyspnea and fatigue were the only grade 3/4 nonhematologic adverse events reported (5% vs 8% and 7% vs 4%, respectively). Based on these preliminary study results, the authors concluded that carfilzomib plus filanesib was a promising steroid-sparing treatment option for patients with RRMM, including those with double-refractory disease. In addition, patients with high AAG levels may be less likely to respond to either filanesib or carfilzomib.
- Zonder JA, et al. ASH 2015. Abstract 728.