NEW YORK – ImmPact Bio on Tuesday said the US Food and Drug Administration has cleared an investigational new drug application allowing it to start a Phase Ib/II study of its autologous, bispecific CD19/CD20 CAR T-cell therapy in patients with active, refractory systemic lupus erythematosus.
The investigational CAR T-cell therapy IMPT-514 is designed to target both CD19 and CD20 using a chimeric antigen receptor and a 4-1BB costimulatory domain. IMPT-514 has the same CAR construct as IMPT-314, which ImmPact is developing as a treatment for patients with aggressive B-cell lymphoma.
"The differentiated bispecific approach of IMPT-514 is designed for broader targeting of autoreactive B cells with the enhanced tissue and lymphoid organ penetration characteristic of CAR T cells," ImmPact CEO and President Sumant Ramachandra said in a statement. "This offers the potential for a one-time treatment administration capable of resetting the immune response for durable remission."
In an investigator-led Phase I study of IMPT-514 at the University of California, Los Angeles, IMPT-514 caused no neurotoxicity and only grade 2 cytokine release syndrome. In preclinical studies, ImmPact successfully manufactured the cell therapy from patients with lupus nephritis and systemic lupus erythematosus and showed that the treatment eliminated autologous B cells.
West Hills, California-based ImmPact will now start a Phase Ib/II dose-escalation trial in patients with active, refractory systemic lupus erythematosus, an autoimmune disease caused when a person's immune system attacks healthy tissue. Patients with lupus nephritis, the most severe form of the disease, are at risk of end-stage renal disease and death.
Patients enrolled in the Phase Ib/II trial must have active, biopsy-confirmed proliferative disease, had at least two prior standard treatments, and have a systemic lupus erythematosus disease activity index score (SLEDAI-2K) of at least 8. Patients with and without active, proliferative nephritis can join the Phase II portion of the study.