The FDA has granted a priority review designation to a supplemental Biologics License Application (sBLA) for daratumumab (Darzalex) in combination with bortezomib (Velcade), thalidomide (Thalomid), and dexamethasone for the treatment of newly diagnosed patients with multiple myeloma who are candidates for autologous stem cell transplant.
The FDA has granted a priority review designation to a supplemental Biologics License Application (sBLA) for daratumumab (Darzalex) in combination with bortezomib (Velcade), thalidomide (Thalomid), and dexamethasone (VTd) for the treatment of newly diagnosed patients with multiple myeloma who are candidates for autologous stem cell transplant (ASCT).1The FDA is expected to make a decision on the sBLA by September 26, 2019.
“Thanks to the strong collaborative effort of the French Intergroupe Francophone du Myelome, the Dutch-Belgian Cooperative Trial Group for Hematology Oncology, and Janssen, should the US FDA approve this sBLA, patients in the United States newly diagnosed with multiple myeloma who are eligible candidates for ASCT may one day also be able to include Darzalex in combination with VTd in their treatment regimen,” Jan van de Winkel, PhD, CEO of Genmab, said in a statement.
The sBLA is based on the results of the randomized, open-label, multicenter phase III CASSIOPEIA trial, in which the daratumumab plus VTd combination is being compared with VTD alone in 1085 previously untreated patients with multiple myeloma who are transplant eligible (MMY3006; NCT02541383). The trial is divided into 2 parts, an induction and consolidation phase followed by a maintenance treatment with daratumumab or observation.
According to results previously released from Genmab,2in the first portion of the trial the daratumumab combination had induced an improved stringent complete response (sCR) rate compared with 20.3% in VTD alone. The safety profile for daratumumab plus VTD was also found to be consistent with known safety profiles of daratumumab and the VTD combination separately.
Updated results from part 1 of the CASSIOPEIA trial are to be presented at the 2019 ASCO Annual Meeting. According to the abstract ahead of the presentation,3the sCR rate was significantly higher with daratumumab plus VTD at 28.9% compared with 20.3% in those treated with VTD alone (odds ratio, 1.60; 95% CI, 1.21-2.12;P= .0010). The median progression-free survival (PFS) has not yet been reached in either arm, but at the 18 months, the PFS rate was 92.7% with the daratumumab combination versus 84.6% with VTD alone.
The trial is the first to ever show a clinical benefit for the combination of daratumumab and standard of care in transplant-eligible newly diagnosed patients with multiple myeloma.
The rate of grade 3/4 treatment-emergent adverse events (TEAEs) were increased with the addition of daratumumab, but the safety profile is still considered acceptable. The most common grade 3/4 TEAEs were neutropenia (27.6% with daratumumab vs 14.7% with VTD alone), lymphopenia (17.0% vs 9.7%, respectively), stomatitis (12.7% vs 16.4%), and thrombocytopenia (11.0% vs 7.4%). Additionally, infusion-related reactions were observed in 35.4% of patients in the daratumumab plus VTD arm.
Daratumumab already has several approved indications for the treatment of patients with multiple myeloma, including the most recent approval for split dosing to allow for the administration of the first infusion of daratumumab over 2 consecutive days or in a single session.