Amgen announced the Phase 3 CANDOR study evaluating KYPROLIS® (carfilzomib) in combination with dexamethasone and DARZALEX® (daratumumab) (KdD) compared to KYPROLIS and dexamethasone alone (Kd) met its primary endpoint of progression-free survival (PFS). The regimen resulted in a 37% reduction in the risk of progression or death in patients with relapsed or refractory multiple myeloma treated with KdD (HR=0.630; 95% CI: 0.464, 0.854; p=0.0014). The median PFS for patients treated with Kd alone was 15.8 months, while the median PFS for patients treated with KdD has not been reached by the cut-off date.
"The potential to combine KYPROLIS with DARZALEX, two powerful targeted agents, represents an additional therapeutic approach for patients with relapsed or refractory multiple myeloma," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "The results from the CANDOR study confirm the potential for KYPROLIS to be used in combination with an anti-CD38 monoclonal antibody."
There was a higher frequency of adverse events reported in KdD, a three-agent regimen, than in Kd, a two-agent regimen. The types of observed adverse events were consistent with the known safety profiles of the individual agents. The most frequently reported treatment-emergent adverse events (greater than or equal to 20%) in the KdD arm were thrombocytopenia, anemia, diarrhea, hypertension, upper respiratory tract infection, fatigue and dyspnea.
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"While treatment advances have improved outcomes for patients with multiple myeloma, there remains a need for additional therapeutic options for patients who have relapsed," said Ajai Chari, M.D., associate professor of medicine, the director of clinical research in the Multiple Myeloma Program and the associate director of clinical research, Mount Sinai Cancer Clinical Trials Office. "CANDOR confirms in a large Phase 3 study the benefit for patients demonstrated in the earlier Phase 1 study using the same combination."
The CANDOR data will be submitted to a future medical meeting and discussed with health authorities in preparation for regulatory submissions.
CANDOR, a randomized, open-label Phase 3 study of KYPROLIS, dexamethasone and DARZALEX (KdD) compared to KYPROLIS and dexamethasone (Kd), has evaluated 466 relapsed or refractory multiple myeloma patients who have received one to three prior therapies. Patients were treated until disease progression. The primary endpoint was PFS, and the key secondary endpoints were overall response rate, minimal residual disease and overall survival. PFS was defined as time from randomization until disease progression or death from any cause.
In the first arm, patients received KYPROLIS twice weekly at 56 mg/m2 and dexamethasone in combination with DARZALEX. In the second arm (control), patients received KYPROLIS twice weekly at 56 mg/m2 and dexamethasone.
CANDOR was initiated as part of a collaboration with Janssen, and under the terms of the agreement, Janssen co-funded the study.
Multiple myeloma is an incurable blood cancer, characterized by a recurring pattern of remission and relapse. It is a rare and life-threatening disease that accounts for approximately one percent of all cancers. Worldwide, approximately 160,000 people are diagnosed with multiple myeloma each year, and 106,000 patient deaths are reported on an annual basis.
Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed.4 KYPROLIS has been shown to block proteasomes, leading to an excessive build-up of proteins within cells.5 In some cells, KYPROLIS can cause cell death, especially in myeloma cells because they are more likely to contain a higher amount of abnormal proteins.