Janssen Research & Development, LLC announced today positive results of a pre-planned interim analysis of the Phase 3 MMY3004 (CASTOR) trial evaluating the efficacy and safety of daratumumab, a CD38-directed monoclonal antibody (mAb), in combination with bortezomib and dexamethasone, compared to bortezomib and dexamethasone alone, in patients with relapsed or refractory multiple myeloma. The interim analysis, conducted by an Independent Data Monitoring Committee (IDMC), found that the daratumumab combination treatment regimen improved progression-free survival (PFS) compared with bortezomib and dexamethasone alone, achieving the primary study endpoint (p < 0.0001). Based on the recommendation of the IDMC, the study will be stopped early. Study patients originally assigned to the standard treatment group (bortezomib plus dexamethasone) will be offered the option of receiving daratumumab following confirmed disease progression. All patients continue to be followed f
or long-term safety and overall survival.
“These results suggest daratumumab could potentially be used in combination with standard therapy in patients with relapsed or refractory multiple myeloma,” said Peter F. Lebowitz, M.D., Ph.D., Global Oncology Head, Janssen Research & Development. “We are especially proud that Janssen was involved in the development of two of the medicines in this trial, daratumumab and bortezomib.” Janssen licensed daratumumab from Genmab A/S and is responsible for development and marketing. Janssen co-developed bortezomib with Takeda Pharmaceutical Company Limited through its wholly owned subsidiary Millennium Pharmaceuticals Inc. and commercializes the treatment outside of the U.S.
MMY3004 is a Phase 3, multinational, open-label, randomized, multicenter, active-controlled study in approximately 490 patients with relapsed or refractory multiple myeloma. Patients were randomized to receive either daratumumab combined with subcutaneous bortezomib (a proteasome inhibitor) and dexamethasone (a corticosteroid), or bortezomib and dexamethasone alone. Participants were treated until disease progression, unacceptable toxicity, or if they had other reasons to discontinue the study. The primary endpoint of the study is PFS.1
These results are planned to be submitted for presentation at an upcoming medical congress, as well as for publication in a peer-reviewed journal. A full study report is being prepared for submission and will be shared with health authorities. Janssen will initiate discussions about the potential for a regulatory submission for this indication. For additional study information, visit ClinicalTrials.gov.
In November 2015, daratumumab (DARZALEX®) was approved by the U.S. Food and Drug Administration 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, or who are double-refractory to a PI and an immunomodulatory agent. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Filed Under: Drug Discovery