Janssen Pharmaceutical announced the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) seeking approval of DARZALEX® (daratumumab) in combination with Kyprolis® (carfilzomib) and dexamethasone (DKd) for relapsed/refractory multiple myeloma. The sBLA is supported by results from the Phase 3 CANDOR study, which compared treatment with DKd to carfilzomib and dexamethasone (Kd) in patients with multiple myeloma who relapsed after one to three prior lines of therapy.
"While we continue to make important strides in the treatment of multiple myeloma, unfortunately most patients will relapse at some point, so it is important that physicians have multiple treatment options and regimens for patients," said Craig Tendler, M.D., Vice President, Late Development and Global Medical Affairs, Janssen Research & Development, LLC. "The results from the CANDOR study support the potential benefit of this DARZALEX-based combination regimen for patients with multiple myeloma who have relapsed from prior treatment."
CANDOR is a randomized, open-label Phase 3 study of DARZALEX® (daratumumab), carfilzomib and dexamethasone (DKd) compared to carfilzomib and dexamethasone (Kd) alone. The study evaluated 466 relapsed or refractory patients with multiple myeloma who had received one to three prior lines of therapy from 120 global sites. Patients were treated until disease progression. The primary endpoint was progression free survival (PFS), and the key secondary endpoints were overall response rate, minimal residual disease and overall survival. PFS was defined as time from randomization until disease progression or death from any cause.
All patients received carfilzomib as a 30-minute intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m2 on days 1 and 2 during cycle 1 and 56 mg/m2 thereafter) and received 40 mg dexamethasone oral or IV weekly (20 mg/m2 for patients aged >75 years). In the treatment arm, DARZALEX® 8 mg/kg was administered IV on days 1 and 2 of cycle 1 and 16 mg/kg IV once weekly for the remaining doses of the first two cycles, then every two weeks for four cycles (cycles 3 to 6), and every four weeks thereafter.
CANDOR is an Amgen-sponsored study and is co-funded by Janssen Research & Development.
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DARZALEX® (daratumumab), the first monoclonal antibody for multiple myeloma approved anywhere in the world, is the only CD38-directed antibody approved to treat multiple myeloma. CD38 is a surface protein that is present in high numbers on multiple myeloma cells, regardless of the stage of disease. DARZALEX® binds to CD38 and inhibits tumor cell growth causing myeloma cell death. DARZALEX® may also have an effect on normal cells. DARZALEX® is being evaluated in a comprehensive clinical development program across a range of treatment settings in multiple myeloma, such as in frontline and relapsed settings. Additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant hematologic diseases in which CD38 is expressed, such as smoldering myeloma.
In the U.S., DARZALEX® received initial FDA approval in November 2015 as a monotherapy for patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double refractory to a PI and an immunomodulatory agent. DARZALEX® received additional approvals in November 2016 in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. In June 2017, DARZALEX® received approval in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a PI. In May 2018, DARZALEX® received approval in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT), making it the first monoclonal antibody approved for newly diagnosed patients with this disease. In June 2019, DARZALEX® received approval in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are transplant ineligible. In September 2019, DARZALEX® received approval in combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for ASCT.
In August 2012, Janssen Biotech, Inc. entered into a global license and development agreement with Genmab, which granted Janssen an exclusive license to develop, manufacture and commercialize DARZALEX®.