Darzalex, Kyprolis, Dexamethasone Combo Extends Time to Disease Progression in Relapsed, Refractory Multiple Myeloma Patients, CANDOR Trial Results Show

A combination of Darzalex (daratumumab), Kyprolis (carfilzomib), and dexamethasone increases the time to disease progression or death in  multiple myeloma patients who already have received one to three prior therapies.

With those results, the CANDOR Phase 3 trial (NCT03158688), co-sponsored by Amgen and Janssen, achieved its primary goal of progression-free survival. The study is comparing the effects of the triple combination to those of Kyprolis and dexamethasone (Kd) in 466 participants with relapsed or refractory multiple myeloma.

Participants receive either the triple combination or Kd until disease progression or death from any cause. Secondary goals include minimal residual disease (when very few cancer cells remain after treatment), overall response rate (percentage of patients who respond to the treatment completely or partially), and overall survival.

Patients treated with the triple combination had 37% less risk of disease progression than those in the control group. The Kd group survived a median of 15.8 months without disease progression, while there were not enough cases of disease progression or death in the group taking the triple combination to calculate progression-free survival.

“The potential to combine Kyprolis with Darzalex, two 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 press release.

“The results from the CANDOR study confirm the potential for Kyprolis to be used in combination with an anti-CD38 monoclonal antibody,” Reese said.

Darzalex, by Janssen, is an antibody therapy that binds to a molecule called CD38, which is produced by myeloma cells, promoting cancer cell death directly and increasing the immune response against myeloma cells.

The proteasome eliminates old faulty proteins within the cell. Proteasome inhibitors like Amgen’s Kyprolis cause these proteins to accumulate, leading to cell death. This specifically affects cancer cells, which accumulate high amounts of faulty proteins.

The group receiving the triple combination reported more adverse events (side effects), such as low platelet and red blood cell count, diarrhea, increased blood pressure, infection in the respiratory tract, fatigue, and shortness of breath, than the Kd group. The observed side effects were similar to those already associated with the individual therapies.

“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 and associate director of clinical research at Mount Sinai Cancer Clinical Trials Office in New York.

“CANDOR confirms in a large Phase 3 study the benefit for patients demonstrated in the earlier Phase 1 study using the same combination.”

The previous Phase 1b trial (NCT01998971) suggested that the triple combination was well-tolerated and effective. Overall, 86% of patients responded to the treatment.

Amgen and Jansen plan to present the preliminary results of CANDOR at an upcoming medical conference and discuss them with health authorities to start preparing regulatory submissions.