The Food and Drug Administration (FDA) has approved daratumumab, a CD38-directed cytolytic antibody, in combination with carfilzomib, a proteasome inhibitor, and dexamethasone (DKd) for the treatment of adults with relapsed or refractory multiple myeloma who have received 1 to 3 previous lines of therapy.
The approval was based on data from the phase 3 CANDOR study. The open-label phase 3 trial included 466 patients who were randomized 2:1 to receive either DKd (n=312) or carfilzomib and dexamethasone (Kd) (n=154). Results showed that after a median follow up of approximately 17 months, DKd was associated with an improvement in progression free survival (PFS; primary end point) compared with Kd (hazard ratio [HR] 0.63; 95% CI, 0.46-0.85; P =.0014). The median PFS and duration of response were not reached in the DKd arm and were 15.8 and 16.6 months in the Kd arm, respectively.
In the intent-to-treat population, the overall response rate was 84% for DKd (n=263; 95% CI, 80-88) compared with 75% (n=115; 95% CI, 67-81) for Kd (1-sided P =.004). Moreover, the DKd arm had a minimal residual disease complete response rate of 12% (n=39; 95% CI, 9-17) at 12 months vs 1.3% (n=2; 95% CI, 0.2-4.6) for Kd (1-sided P <.0001).
Additionally, findings from the open-label, multicohort phase 1b EQUULEUS trial, in which 85 patients received DKd, supported the use of a once-weekly dosing regimen for carfilzomib. Results showed an overall response rate of 81% (n=69; 95% CI, 71-89), of which 21% (n=18) had stringent complete response, 14% (n=12) had complete response, 33% (n=28) had very good partial response, and 13% (n=11) had partial response.
Commenting on the approval, Saad Z. Usmani, MD, director of clinical research in hematologic malignancies; director of plasma cell disorders; clinical professor of medicine, Atrium Health’s Levine Cancer Institute, said: “As a clinician, having the DKd regimen as an option means we can now combine 2 efficacious, targeted agents in a new, immunomodulatory drug-free triplet regimen that has demonstrated deep and durable responses for patients upon relapse.”
- Genmab announces Janssen granted US FDA approval for Darzalex® (daratumumab) in combination with carfilzomib and dexamethasone in relapsed or refractory multiple myeloma. https://www.globenewswire.com/news-release/2020/08/20/2081705/0/en/Genmab-Announces-Janssen-Granted-U-S-FDA-Approval-for-DARZALEX-daratumumab-in-Combination-with-Carfilzomib-and-Dexamethasone-in-Relapsed-or-Refractory-Multiple-Myeloma.html. Accessed August 21, 2020.
- FDA Approves new Kyprolis® (carfilzomib) combination regimen with Darzalex® (daratumumab) and dexamethasone in both once- and twice-weekly dosing regimens. https://www.prnewswire.com/news-releases/fda-approves-new-kyprolis-carfilzomib-combination-regimen-with-darzalex-daratumumab-and-dexamethasone-in-both-once–and-twice-weekly-dosing-regimens-301116047.html. Accessed August 21, 2020.
- Darzalex [package insert]. Horsham, PA: Janssen Biotech, Inc; 2020.