Summary
Initial clinical data for REGN5458, a BCMAxCD3 bispecific antibody, in patients with relapsed or refractory (R/R) multiple myeloma were presented at the 2019 ASH Annual Meeting. BCMA (B-cell maturation antigen) is a protein that is typically over-expressed on multiple myeloma cells. REGN5458 is designed to bind to BCMA on multiple myeloma cells and the CD3 receptor on T cells, bridging them together and activating T-cell killing of the cancer cell.
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Original Article
REGN5458 (BCMAxCD3) Shows Positive Preliminary Results in Multiple Myeloma
Oncology Times
Initial clinical data for REGN5458, a BCMAxCD3 bispecific antibody, in patients with relapsed or refractory (R/R) multiple myeloma were presented at the 2019 ASH Annual Meeting. BCMA (B-cell maturation antigen) is a protein that is typically over-expressed on multiple myeloma cells. REGN5458 is designed to bind to BCMA on multiple myeloma cells and the CD3 receptor on T cells, bridging them together and activating T-cell killing of the cancer cell.
Results highlighted the first two dose groups (3 mg and 6 mg weekly doses). Patients had a median of seven lines of prior systemic therapy, and all had failed CD38 antibody treatment. Responses were observed in 4 of 7 (57%) patients, including 3 of 4 (75%) in the 6 mg dose group. In the 6 mg dose group, 2 patients (50%) were also minimal residual disease (MRD)-negative, meaning that no cancer cells were detectable in their bone marrow.
As of data cutoff, there have been no neurotoxicity, dose-limiting toxicities or treatment discontinuations due to adverse events (AEs). The most common treatment-emergent AEs were lymphopenia (n=5), anemia (n=4), and thrombocytopenia and cytokine release syndrome (n=3 each). Grade 3 or higher treatment-emergent AEs were seen in 5 patients and included lymphopenia (n=3), hypertension (n=2) and anemia, atrial fibrillation, fatigue, febrile neutropenia, pain in extremity, septic shock, and thrombocytopenia (n=1 each).
Multiple myeloma is the second most common blood cancer, with approximately 32,000 and 138,500 new diagnoses in the U.S. and world, respectively. It is characterized by the proliferation of cancerous plasma cells (multiple myeloma cells) that crowd out healthy blood cells in the bone marrow, infiltrate other tissues and cause potentially life-threatening organ injury. Recent advances, such as CD38 antibody treatment, have increased life expectancy of patients from 3-4 years to 7-8 years. Despite this, multiple myeloma remains incurable, and most patients will experience relapse and require additional therapy.
REGN5458 monotherapy is being investigated in an open-label, phase I/II dose-escalation trial in patients with R/R multiple myeloma who have exhausted all therapeutic options, including proteasome inhibitors, immunomodulatory drugs, and CD38 antibody treatments. The phase I portion is assessing safety, tolerability, and dose-limiting toxicities. Beyond the initial dose groups presented at ASH, additional dose groups are being evaluated to determine a recommended phase II dose regimen. The phase II portion will further assess REGN5458 anti-tumor activity and safety.
Among the patients being enrolled are those with heavily pre-treated multiple myeloma, including those with extra-medullary and non-secretory disease.
In multiple myeloma clinical trials, treatment effectiveness is typically assessed by overall response rate (ORR; with response types categorized by the level of reduction in myeloma protein) and the rate of conversion to negative MRD. For ORR, myeloma protein levels in the blood are reduced by more than 50 percent in partial responses (PR) and 90 percent in very good PR (VGPR), while complete responses are defined as no evidence of myeloma protein and ≤5 percent of plasma cells in the bone marrow. MRD is measured separately from ORR, and MRD negativity is defined as the absence of myeloma cells within 100,000 bone marrow cells.