A supplemental biologics license application has been submitted to the FDA for the potential approval of a new indication for daratumumab. The sBLA was for the combination of daratumumab plus bortezomib, thalidomide, and dexamethasone for the treatment of newly diagnosed patients with multiple myeloma who are eligible for autologous stem cell transplant.
A supplemental biologics license application (sBLA) has been submitted to the FDA for the potential approval of a new indication for daratumumab (Darzalex). The sBLA was for the combination of daratumumab plus bortezomib (Velcade), thalidomide (Thalomid), and dexamethasone (VTD) for the treatment of newly diagnosed patients with multiple myeloma who are eligible for autologous stem cell transplant (ASCT).1
The submission is based off of positive findings from the phase III CASSIOPEIA trial (MMY3006; NCT02541383), which has demonstrated an increase in the number of patients who achieved a stringent complete response (sCR) with the 4-drug regimen compared with VTD alone. This met the primary endpoint of part 1 of the study.
"This submission marks an important step in the pursuit of potential treatments for newly diagnosed patients living with multiple myeloma, as Darzalex has the potential to improve clinical outcomes in combination with a standard regimen," said Yusri Elsayed, MD, MHSc, PhD, vice president, Hematologic Malignancies Disease Area Leader, Janssen Research & Development, in a statement. "We look forward to working closely with the FDA during review of the submission with the goal of bringing a new treatment option to newly diagnosed patients who are transplant eligible."
Topline results of the CASSIOPEIA trial were announced in a press release from Genmab, the company that co-develops daratumumab with Janssen, in October 2018.2The findings indicated that in part 1 of the phase III trial, the rate of sCR among patients treated with daratumumab plus VTD was 28.9% compared with 20.3% in those treated with VTD alone (odds ratio, 1.60; 95% CI, 1.21-2.12;P≤.001).
The safety profile for daratumumab in combination with VTD has been consistent with the known safety profiles of both VTD and daratumumab.
The randomized, open-label, multicenter phase III trial enrolled 1085 patients with previously untreated multiple myeloma who were symptomatic and eligible for high-dose chemotherapy and ASCT. Patients were randomized to either daratumumab plus VTD or VTD treatment alone for 4 cycles of induction followed by transplantation and an additional 2 cycles of treatment as consolidation as part 1 of the trial. In phase 2, patients who respond to treatment are re-randomized to either daratumumab alone as maintenance therapy or observation. Maintenance of 16 mg/kg of daratumumab was to be given every 8 weeks for up to 2 years. The primary endpoint of part 2 is progression-free survival.
Secondary endpoints for the trial include progression-free survival from first randomization, time to progression, post-ASCT/consolidation CR rate, post-induction treatment sCR rate, time to subsequent progression on next line of therapy after progression on the CASSIOPEIA trial, and overall survival.
Additional findings from the trial are expected to be submitted for presentation at an upcoming medical conference and for publication in a peer-reviewed journal.
The CD38-directed monoclonal antibody already has several approved indications for the treatment of patients with multiple myeloma, including themost recent approval for split dosingto allow for the administration of the first infusion of daratumumab over 2 consecutive days or in a single session.