Amgen acknowledged today that its Kyprolis® (carfilzomib) failed a Phase III trial comparing the marketed cancer drug to Velcade® (bortezomib) in combination with melphalan and prednisone in newly diagnosed multiple myeloma patients.
Kyprolis missed its primary endpoint in the Phase III CLARION trial of superior progression-free survival (PFS) to Velcade—marketed in the U.S. by Takeda Oncology—with melphalan and prednisone after 54 weeks of treatment in patients with newly diagnosed multiple myeloma who were ineligible for hematopoietic stem cell transplantation, Amgen said.
The Kyprolis combination yielded a median PFS of 22.3 months, compared with 22.1 months for the Velcade combination.
CLARION was a multicenter, open-label, randomized study in which 955 patients were randomized 1:1 to receive the combination of Kyprolis, melphalan, and prednisone (KMP) or the combination of Velcade, melphalan, and prednisone (VMP) for 54 weeks. The median patient age was 72.
While fatal treatment-emergent adverse events occurred in 6.5% of KMP patients and 4.3% of VMP patients, the Kyprolis combo fared better in a secondary endpoint, incidence of Grade 2 or higher peripheral neuropathy, which was 2.5% in the KMP treatment arm and 35.1% in the VMP arm. Incidence of Grade 3 or higher adverse events was 74.7% for KMP patients and 76.2% for VMP patients.
Detailed data “will be submitted to a future medical conference and for publication,” Amgen added.
“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,” Sean E. Harper, M.D., Amgen’s evp of R&D, said in a statement. That data showed a PFS of 18.7 months for a Kyprolis– dexamethasone combination vs. 9.4 months for Velcade–dexamethasone.
“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.,” Dr. Harper added. “We remain committed to exploring Kyprolis in combination with other agents to advance the treatment of multiple myeloma.”
Another Phase III comparison trial involving Kyprolis and Velcade is underway—the E1A11 or ENDURANCE study comparing Kyprolis to Velcade in combination with lenalidomide plus dexamethasone in newly diagnosed multiple myeloma patients. More than 750 institutions nationwide are currently enrolling patients in the study (NCT01863550), which is being carried out by the ECOG-ACRIN Cancer Research Group with funding by the NIH’s National Cancer Institute (NCI) and its National Clinical Trials Network.