A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma

David S. Siegel, Thomas Martin, Michael Wang, Ravi Vij, Andrzej J. Jakubowiak, Sagar Lonial, Suzanne Trudel, Vishal Kukreti, Nizar Bahlis, Melissa Alsina, Asher Chanan-Khan, Francis Buadi, Frederic J. Reu, George Somlo, Jeffrey Zonder, Kevin Song, A. Keith Stewart, Edward Stadtmauer, Lori Kunkel, Sandra Wear, Alvin F. Wong, Robert Z. Orlowski and Sundar Jagannath


Carfilzomib is a next-generation, selective proteasome inhibitor being evaluated for the treatment of relapsed and refractory multiple myeloma. In this open-label, single-arm phase 2 study (PX-171-003-A1), patients received single-agent carfilzomib 20 mg/m2 intravenously twice weekly for 3 of 4 weeks in Cycle 1, then 27 mg/m2 for ≤12 cycles. Primary endpoint was overall response rate (ORR; ≥partial response). Secondary endpoints included clinical benefit response rate (≥minimal response), duration of response (DOR), progression-free survival, overall survival (OS), and safety. 266 patients were evaluable for safety, 257 for efficacy; 95% were refractory to their last therapy; 80% were refractory or intolerant to both bortezomib and lenalidomide. Patients had median of 5 prior lines of therapy, including bortezomib, lenalidomide, and thalidomide. ORR was 23.7% with median DOR of 7.8 months. Median OS was 15.6 months. Adverse events (AEs) were manageable without cumulative toxicities. Common AEs were fatigue (49%), anemia (46%), nausea (45%), and thrombocytopenia (39%). 33 patients (12.4%) experienced peripheral neuropathy, primarily Grades 1/2. Thirty-three patients (12.4%) withdrew due to an AE. Durable responses and an acceptable tolerability profile in this heavily-pretreated population demonstrate the potential of carfilzomib to offer meaningful clinical benefit. Registered at as #NCT00511238.

  • Submitted May 2, 2012.
  • Accepted July 16, 2012.