New proteasome inhibitor tested in relapsed/refractory myeloma

NORWALK, Connecticut—The Multiple Myeloma Research Consortium (MMRC) and Proteolix, Inc. (South San Francisco, California) have begun enrolling patients in a multicenter phase II clinical trial of Proteolix's proteasome inhibitor carfilzomib (PR-171) in patients with relapsed and refractory multiple myeloma.

Several MMRC member institutions, along with other centers, will participate in the study, under the MMRC leadership of Melissa Alsina, MD, of the H. Lee Moffitt Cancer Center & Research Institute, Tampa. The additional MMRC sites are City of Hope, Emory University, the Cancer Center at Hackensack University Medical Center, Mayo Clinic, Princess Margaret Hospital/University Health Network, Saint Vincent's Comprehensive Cancer Center, University of Michigan, and Washington University.

The trial will evaluate the overall response rate for two cycles of carfilzomib in patients with multiple myeloma who have previously received specific FDA-approved therapies, have relapsed after two or more of such therapies, and are refractory to the most recently received therapy. Secondary objectives include safety and tolerability, clinical benefit response, time to progression, duration of response, progression-free survival, and best overall response rate throughout the study. Patients will receive carfilzomib twice weekly for 3 weeks every 28 days.

In the coming weeks, the MMRC and Proteolix will also begin enrollment in an open-label, single-arm phase II study of carfilzomib in patients with relapsed multiple myeloma who will be stratified by bortezomib (Velcade) history.

Carfilzomib is a structurally and mechanistically novel proteasome inhibitor that exhibits a high level of selectivity for the unique N-terminal threonine active sites within the proteasome, Proteolix said in a news release. Carfilzomib is similar to bortezomib in that it is a potent inhibitor of the proteasome chymotrypsin-like activity, but unlike bortezomib, carfilzomib has shown minimal cross-reactivity with the other catalytic sites within the proteasome or across other protease classes, the company said. Phase I clinical studies confirmed that patients who had relapsed or progressed following multiple therapies can still achieve durable anti-tumor responses with carfilzomib.

In addition to the two phase II single-agent trials in myeloma and ongoing studies in lymphoma, a clinical trial in solid tumors and a trial exploring carfilzomib in combination with an FDA-approved agent will be initiated by the end of the year.

The MMRC was founded in 2004 by Kathy Giusti with the help of the scientific community. It is a sister organization to the Multiple Myeloma Research Foundation. For more information, please visit www.themmrc.org.