Date: 2015-08-27
Type of information: Publication of results in a medical journal
phase: 1-2
Announcement: publication of results in The New English Journal of Medicine
Company: Genmab (Denmark)
Product: daratumumab
Action
mechanism: monoclonal antibody. Daratumumab is a human CD38 monoclonal antibody with broad-spectrum killing activity. Daratumumab is in clinical development for multiple myeloma. It targets the CD38 molecule which is highly expressed on the surface of multiple myeloma cells and may also have potential in other cancers on which CD38 is expressed, including diffuse large B-cell lymphoma, chronic lymphocytic leukemia, acute lymphoblastic leukemia, plasma cell leukemia, acute myeloid leukemia, follicular lymphoma and mantle cell lymphoma. Daratumumab has been granted Breakthrough Therapy Designation from the FDA for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) or who are double refractory to a PI and an IMiD. In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop, manufacture and commercialize daratumumab.
Disease: relapsed/refractory multiple myeloma
Therapeutic area: Cancer - Oncology
Country:
Trial
details: This two-part, Phase I/II, open-label study enrolled 32 patients in part 1, and 72 patients in part 2, 42 of which were in the 16 mg/kg dose group. Part 1 was a dose-escalation study with patients receiving weekly doses of daratumumab between 0.005 and 24 mg/kg of daratumumab. In part 2, 8 mg/kg and 16 mg/kg daratumumab were administered with different schedules. The primary endpoint of the study was safety. Secondary endpoints were pharmacokinetics, objective response according to International Myeloma Working Group (IMWG) uniform response criteria for myeloma, relative reductions in M-protein and free light chains, time to progression, response duration, progression-free and overall survival.
Latest
news: * On August 27, 2015, Genmab announced the New England Journal of Medicine (NEJM) has published the full data set from the initial Phase I/II study with daratumumab monotherapy treating patients with relapsed or refractory multiple myeloma. Patients that received 16 mg/kg in part 2 of the study had a median of 4 prior lines of therapy and 64% of these patients were refractory to both proteasome inhibitors (PIs) and immunomodulatory (IMiD) drugs, which are current standard of care treatments for multiple myeloma. The data showed a 36% response rate in the 16 mg/kg group in part 2 of the study, with responses that deepened over time. Sixty five percent of patients in this group that responded to treatment were progression-free twelve months following the start of treatment. For all patients in part 2, pneumonia and thrombocytopenia were the most common grade 3/4 adverse events (AEs; ?5%). Infusion-related reactions were mild with no dose-dependent adverse events. In part 1 of the study, no maximum tolerated dose was identified up to 24 mg/kg.
Following this study, 16 mg/kg was chosen as the dose to be used in future daratumumab clinical studies. Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab.
Data from this study has been included in the Biologics License Application (BLA) submitted by Janssen to the FDA for daratumumab as a treatment for patients with multiple myeloma who have received at least three prior lines of therapy including both a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) or who are double refractory to a PI and an IMiD. The BLA submission was completed on July 9th 2015.
