An application has been submitted seeking U.S. approval of Darzalex (daratumumab) in combination with standard pre-transplant therapy to treat newly diagnosed multiple myeloma patients who are eligible for a stem cell transplant.
Janssen‘s supplemental Biologics License Application to the U.S. Food and Drug Administration (FDA) is for a combination of Darzalex plus Velcade (bortezomib), thalidomide, and dexamethasone (collectively known as VTd). The submission is based on data from the CASSIOPEIA Phase 3 trial (NCT02541383), where the combination increased the number of patients showing no signs of cancer after a stem cell transplant.
“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,” Yusri Elsayed, MD, PhD, a vice president at Janssen Research & Development, said in a press release.
“We look forward to working closely with the FDA during review of the submission,” Elsayed added.
Darzalex, originally developed by Genmab, is an antibody that targets CD38, a cell surface protein found in high numbers in multiple myeloma cells. Darzalex binds to CD38 to block growth and cause death of myeloma cells.
The CASSIOPEIA trial was designed to determine if adding Darzalex to standard high-dose chemotherapy was better than VTd alone at eliminating traces of cancer after an autologous stem cell transplant — a procedure where patients receive their own stem cells.
The open-label, multicenter study included 1,085 newly diagnosed patients, who were first randomized to receive Darzalex plus VTd or VTd alone as an induction treatment. All patients then received a stem cell transplant, followed by consolidation therapy with two cycles of either Darzalex plus VTd or VTd alone.
The primary goal was to assess the proportion of patients achieving a stringent complete response — defined as no signs of cancer cells or myeloma antibodies — after induction and consolidation therapy.
Investigators found that Darzalex increased the number of patients with no signs of cancer after transplant from 20.3% to 28.9%.
In the ongoing second part of the trial, the patients who showed a partial response or better in part one will either be on maintenance treatment with Darzalex for up to two years, or be observed with no additional therapy. The primary goal in this second part is progression-free survival, which refers to the length of time patients live without cancer progression.
Earlier this month, Janssen filed a separate application to obtain FDA approval for Darzalex in combination with Revlimid (lenalidomide) and dexamethasone for newly diagnosed patients ineligible for a stem cell transplant. This application is supported by results of the MAIA Phase 3 trial (NCT02252172), which showed that the triple combination lessened the risk of disease progression or death by 45% compared with standard care, and doubled the number of patients with complete cancer disappearance.
In the U.S., Darzalex was initially approved in 2015 as a stand-alone treatment for patients who have received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who do not respond to both types of treatment.
More recent FDA approvals — in 2016 and 2017 — for previously treated patients with multiple myeloma included Darzalex in combination with Revlimid/Velcade and dexamethasone, and with Pomalyst (pomalidomide) and dexamethasone. In May 2018, the FDA approved a combination of Darzalex, Velcade, Alkeran (melphalan) and prednisone for patients with newly diagnosed multiple myeloma who are ineligible for stem cell transplants.