Amgen recently announced early phase 3 CANDOR study data, showing the triple-drug combination of carfilzomib (Kyprolis), along with dexamethasone and daratumumab (Darzalex, sold by Janssen), met its primary end point of progression-free survival in patients with relapsed or refractory multiple myeloma, with a 37% reduction in the risk of progression or death.
Amgen recently announced early phase 3 CANDOR study data, showing the triple-drug combination of carfilzomib (Kyprolis), along with dexamethasone and daratumumab (Darzalex, sold by Janssen), met its primary end point of progression-free survival (PFS), in patients with relapsed or refractory multiple myeloma (RRMM), with a 37% reduction in the risk of progression or death.
Amgen's proteasome inhibitor carfilzomib is approved for RRMM; the CANDOR data will be submitted to a future medical meeting and discussed with the FDA.
The company released the results comparing carfilzomib and dexamethasone alone (Kd) to the triple therapy (KdD) (hazard ratio [HR] = .630; 95% CI, 0.464-0.854; P = .0014) at the 17th International Myeloma Workshop (IMW) 2019 in Boston, Massachusetts last week.
The median PFS for patients treated with Kd alone was 15.8 months; the median PFS for patients treated with KdD has not been reached by the cut-off date.
"The potential to combine Kyprolis with Darzalex, 2 powerful targeted agents, represents an additional therapeutic approach for patients with relapsed or refractory multiple myeloma," David M. Reese, MD, executive vice president of research and development at Amgen, said in a statement. "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 AEs reported in KdD than in Kd; the types of AEs were consistent with the known safety profiles of the drugs. The most frequently reported treatment-emergent AEs (greater than or equal to 20%) in the KdD arm were thrombocytopenia, anemia, diarrhea, hypertension, upper respiratory tract infection, fatigue, and dyspnea.
"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, MD, 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."
Amgen released a variety of analyses about other carfilzomib trials at the Boston meeting. Carfilzomib was approved in 2012 under an accelerated FDA approval pathway in which patients with RRMM were treated with carfilzomib plus lenalidomide with low-dose dexamethasone or lenalidomide and low-dose dexamethasone.
A study assessing post hoc patient outcomes by frailty status found that carfilzomib-based regimens improved PFS and overall survival in patients treated with lenalidomide-dexamethasone or dexamethasone, compared with bortezomib-dexamethasone, in all frailty subgroups.1
A pooled analysis of individual patient data provided an overall assessment of clinical outcomes for patients with RRMM using a triple combination of carfilzomib, pomalidomide and dexamethasone (KPd), because the need for the need for lenalidomide-sparing regimens is increasing.2 Patient-level data from 2 single-arm phase 1/2 studies of KPd in RRMM were combined. The median number of prior lines of therapy in the pooled population was 4 and ORR for the individual studies was 77% and 70%, respectively with a pooled rate of 73%.
The pooled proportion of patients who had very goodpartial response or better (≥VGPR) was 35%. Median OS was 29.6 months and 12- and 24-month PFS rates were 49% and 20%, respectively, in the pooled population. ORR was 79% and the rate of ≥VGPR was 45% in patients at first relapse (n = 22). In patients with 1-3 prior lines of therapy (n = 89), ORR was 80% and ≥VGPR was 40%. In patients with ≥2 prior lines of therapy (n = 160), ORR was 72% and ≥VGPR was 34%. ORR was 70% and ≥VGPR was 30% in patients with ≥2 prior lines of therapy who had received both prior lenalidomide and a prior proteasome inhibitor (n = 141).
Amgen also said the first phase 1 study of AMG 176, a selective MCL-1 inhibitor, in on a “clinical hold” after to evaluate cardiac toxicity.