An open-label single-arm pilot phase II study (PX-171-003-A0) of low-dose, single-agent carfilzomib in patients with relapsed and refractory multiple myeloma

Background: Carfilzomib is a next-generation selective proteasome inhibitor that irreversibly binds its target and has demonstrated single-agent activity in patients with bortezomib-resistant multiple myeloma (MM). PX-171-003-A0, an open-label single-arm multicenter pilot phase II study, enrolled 46 patients with relapsed MM after < 2 previous therapies including bortezomib and an immunomodulator (thalidomide or lenalidomide) and disease refractory to the last treatment regimen preceding study entry. Methods: Patients received carfilzomib 20 mg/m² intravenously on days 1, 2, 8, 9, 15, and 16 every 28 days for up to 12 cycles. Responses in 42 evaluable patients were assessed per International Myeloma Working Group Uniform Response Criteria, with minimal response assessed per European Group for Blood and Marrow Transplantation (EBMT) criteria. Results: The primary endpoint of best ORR was 16.7%, including 7 partial responses. Median duration of response was 7.2 months. Clinical benefit response (CBR) rate was 23.8% with a median duration of response of 13.8 months. The most common treatment-emergent adverse events (AEs) of any grade were anemia (73.9%), fatigue (69.6%), and thrombocytopenia (50.0%). Notably, peripheral neuropathy and neuropathy-related AEs were generally mild and infrequent. Conclusion: This pilot study was the first phase II single-agent trial conducted with carfilzomib. Based on these findings, the study was amended to test a higher carfilzomib dose in an additional 250 patients (PX-171-003-A1).