Pfizer PF-06863135 in Multiple Myeloma
by Dr. C.H. Weaver M.D. 12/2020
The investigational B-cell maturation antigen (BCMA) CD3-targeted bispecific antibody from Pfizer was reported to have achieve a 83% response rate at the highest dose level in advanced multiple myeloma patients at the December 2020 American Society of Hematology annual meeting.
PF-06863135 is a bispecific antibody designed to bind to BCMA which is highly expressed on the surface of multiple myeloma cells, and the CD3 receptor found on the surface of cancer-fighting T cells, bridging them together to activate an immune response.
Bispecific Antibodies are antibodies with two arms. One arm of the drug attaches to a specific protein on the tumor cell (BCMA). The other arm of the attaches to and activates immune cells (CD3) in the patient to kill the cancer cells. The antibody constructs essentially help the body’s immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells placing the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). There are several “bispecific” antibodies in development that target BCMA.
PF-06863135 was evaluated at several dose levels and found to be well tolerated and to achieve a 83% response rate at the highest dose rate in 30 patients wth advanced myeloma.
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Raje NS, et al. Safety, Clinical Activity, Pharmacokinetics, and Pharmacodynamics from a Phase I Study of PF-06863135, a B-Cell Maturation Antigen (BCMA)-CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma. Blood (2019) 134 (Supplement_1):1869.