Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) today announced results from an ongoing Phase 2 study, known as the 004 study, of the company's lead proteasome inhibitor, carfilzomib. Results demonstrated promising overall response rates when carfilzomib was administered as a single agent in patients with relapsed and/or refractory multiple myeloma. These data were presented at the 51st annual meeting of the American Society of Hematology (ASH) in New Orleans.
Patients were divided into two populations: 73 evaluable patients with relapsed and/or refractory multiple myeloma who had not received prior bortezomib (Velcade®) treatment, classified as bortezomib-naive patients, and 33 evaluable patients with relapsed and/or refractory disease following bortezomib treatment, classified as bortezomib-treated patients.
Michael Wang, M.D., assistant professor, department of lymphoma and myeloma at the University of Texas M. D. Anderson Cancer Center and co-investigator of the study, reported that the bortezomib-naive patients when treated with carfilzomib achieved an overall response rate (ORR) of 46 percent in 54 evaluable patients at 20 mg/m2 and 53 percent in 19 evaluable patients with dose escalation to 27 mg/m2. Additionally, Dr. Wang reported interim results for secondary endpoints at the 20 mg/m2 dose, including time-to-progression (TTP) of 7.6 months and duration of response (DoR) of 8.4 months.
David Siegel, M.D., Ph.D., division chief of myeloma at the John Theurer Cancer Center and co-investigator of the study, reported that 33 evaluable patients who were previously treated with bortezomib achieved an ORR of 18 percent when administered carfilzomib. Dr. Siegel reported interim results for a secondary endpoint of TTP at 5.3 months and DoR of more than 9 months. More than 20 percent of patients were able to complete the full 12 cycles (48 weeks) of therapy in both studies without cumulative side effects.
"These interim results suggest that carfilzomib could benefit patients with multiple myeloma who are no longer responding to current therapies," said Dr. Siegel. "Additionally, given the low incidence of neuropathy and generally mild and manageable adverse events in this trial, these results suggest that increasing the dosage of carfilzomib up to 27 mg/m2 is well tolerated despite a high degree of coexisting medical conditions, such as renal insufficiency and diabetes."
Overall, treatment with carfilzomib was well tolerated and no unexpected side effects occurred. The most common grade 3 treatment-related adverse events occurred in less than 5 percent of the patients and included fatigue, pneumonia, neutropenia, lymphopenia and anemia. Peripheral neuropathy of any grade was rare and there were no grade 4 adverse events observed.
Other findings from the two populations include: