The phase 3 CLARION trial, which evaluated an investigational regimen of carfilzomib (Kyprolis, Amgen), melphalan, and prednisone (KMP) versus bortezomib (Velcade, Takeda Oncology), melphalan, and prednisone (VMP) for 54 weeks in patients with newly diagnosed multiple myeloma who were ineligible for hematopoietic stem-cell transplant, did not meet its primary endpoint of superiority in progression-free survival (PFS).
Median PFS was 22.3 months for KMP versus 22.1 months for VMP (hazard ratio [HR], 0.91, 95% confidence interval [CI], 0.75–1.10). While the data for overall survival, a secondary endpoint, are not yet mature, the observed HR (KMP versus VMP) was 1.21 (95% 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 carfilzomib. The incidence of grade 3 or higher adverse events was 74.7% in the KMP arm and 76.2% in the VMP arm. Fatal treatment-emergent adverse events occurred in 6.5% of KMP patients and 4.3% of VMP patients. The incidence of grade 2 or higher peripheral neuropathy, a secondary endpoint, was 2.5% in the KMP arm and 35.1% 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, MD, 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."
Amgen supports a number of investigator-sponsored studies, including a phase 3 study evaluating carfilzomib in combination with lenalidomide (Revlimid, Celgene) plus dexamethasone (KRd) versus bortezomib in combination with lenalidomide plus dexamethasone (VRd) in newly diagnosed multiple myeloma patients. This trial, called E1A11 or ENDURANCE, is being conducted independently by the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network Cancer Research Group with funding provided by the National Cancer Institute and its National Clinical Trials Network. Over 750 institutions nationwide are enrolling patients in the study (NCT01863550).
Source: Amgen; September 27, 2016.