Disease: Relapsed/Refractory Multiple Myeloma, MM, (NCT04093596)
Multiple myeloma is a cancer that develops in the bone marrow, the spongy tissue found in the centre of most bones. Multiple myeloma is characterized by abnormalities in plasma cells, a type of white blood cell. These abnormal cells multiply out of control, increasing from about one percent of cells in the bone marrow to the majority of bone marrow cells. The abnormal cells form tumours within the bone, causing bone pain and an increased risk of fractures.
Multiple myeloma occurs in approximately 4 per 100,000 people per year; there are currently about 100,000 affected individuals in the United States.
A Single-Arm, Open-Label, Phase 1 Study of the Safety, Efficacy, and Cellular Kinetics/Pharmacodynamics of ALLO-715 to Evaluate an Anti-BCMA Allogeneic CAR T Cell Therapy in Subjects With Relapsed/Refractory Multiple Myeloma
The purpose of the UNIVERSAL study is to assess the safety, efficacy, cell kinetics, and immunogenicity of ALLO-715 in adults with relapsed or refractory multiple myeloma after a lymphodepletion regimen of ALLO-647 in combination with fludarabine and/or cyclophosphamide, or ALLO-647 alone.
ALLO-715 is an allogeneic CAR T cell therapy targeting BCMA
ALLO-647 is a monoclonal antibody that recognizes a CD52 antigen
ALLO-715 is an investigational off-the-shelf CAR-T therapy using T-cells harvested from healthy donors.
These cells are isolated in a manufacturing facility, engineered to express synthetic T cell receptors, CARs (chimeric antigen receptors) to recognize and destroy cancer cells, and modified via gene editing to limit autoimmune response when given to a patient.
The harvested T-cells are edited using TALENs (Cellectis' technology) to knockout two genes.
T cell receptor gene is knocked out to minimize risk of GvHD (Graft versus Host Disease).
The CD52 gene is knocked out to render the CAR T product resistant to anti-CD52 antibody treatment. ALLO-647, anti-CD52 monoclonal antibody, is designed to suppress the host immune system and allow the AlloCAR-T TM therapy to stay engrafted in order to achieve full therapeutic impact.
ALLO-715 recognize BCMA, a cell-surface protein universally expressed on malignant plasma cells.
The safety profile of allogeneic BCMA CAR Ts was further enhanced by incorporating a CD20 mimotope-based intra-CAR off-switch allowing investigators to destroy genetically-modified T-cells in the presence of Rituxan (rituximab), if needed.