Amgen has announced top-line results of the Phase 3 CLARION trial, which evaluated an investigational regimen of KYPROLIS® (carfilzomib), melphalan and prednisone (KMP) versus Velcade® (bortezomib), melphalan and prednisone (VMP) for 54 weeks in patients with newly diagnosed multiple myeloma who were ineligible for hematopoietic stem-cell transplant. The trial did not meet the primary endpoint of superiority in progression-free survival (PFS) (median PFS 22.3 months for KMP versus 22.1 months for VMP, HR = 0.91, 95 percent CI, 0.75 - 1.10). While the data for overall survival, a secondary endpoint, are not yet mature, the observed hazard ratio (KMP versus VMP) was 1.21 (95 percent CI, 0.90 - 1.64). Neither result was statistically significant.
Overall, the adverse events in the KMP arm were consistent with the known safety profile of KYPROLIS. The incidence of Grade 3 or higher adverse events was 74.7 percent in the KMP arm and 76.2 percent in the VMP arm. Fatal treatment-emergent adverse events occurred in 6.5 percent of KMP patients and 4.3 percent of VMP patients. The incidence of Grade 2 or higher peripheral neuropathy, a secondary endpoint, was 2.5 percent in the KMP arm and 35.1 percent in the VMP arm.
"Based on studies in the KYPROLIS label, including the ENDEAVOR study, a head-to-head comparison of KYPROLIS to Velcade in patients with relapsed or refractory multiple myeloma, we know KYPROLIS to be a major advance in proteasome inhibitor therapy," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "The CLARION results, generated in the context of a melphalan-containing regimen, are disappointing; especially given the robust data we've seen in the second-line setting. However, the myeloma landscape has changed dramatically since the design of the CLARION study with very few newly diagnosed patients treated with melphalan-based regimens, particularly in the U.S. We remain committed to exploring KYPROLIS in combination with other agents to advance the treatment of multiple myeloma."