FDA clears investigational new drug application for ACLX-001 for multiple myeloma

On April 6, 2021, it was announced that the U.S. Food and Drug Administration (FDA) cleared an investigational new drug (IND) application for ACLX-001, a controllable cell therapy, for the treatment of multiple myeloma (MM). This IND application was based on results from the phase I trial (NCT04155749) of CART-ddBCMA, a BCMA-directed chimeric antigen receptor (CAR) T cell with a non-scFv binding domain that has been deimmunized for the treatment of relapsed and refractory (R/R) MM.¹

ACLX-001^2,3

• ACLX-001 is composed of ARC-T cells and a bivalent SparX protein that targets BCMA (utilizing the same antigen-binding domain as CART-ddBCMA).
  • SparX proteins consist of novel binding domains (specific to antigens on diseased cells) and a universal tag that is recognized by ARC-T cells, and thus flags diseased cells for killing.
  • ARC-T cells are autologous T cells engineered to express a novel binding domain that recognizes SparX proteins and, once bound, become activated to kill the flagged cells.

NCT04155749^1,4

• Non-randomized, open label, multicenter, phase I study of CART-ddBCMA for the treatment of R/R MM
• Start date: November 18, 2019
• Estimated completion date: November 1, 2035
• Primary outcome measure: Incidence of treatment-emergent adverse events, including dose-limiting toxicities
• Secondary outcome measures: Best overall response and overall response rate by the International Myeloma Working Group (IMWG) criteria

Results¹

• Results for the first six patients treated with CART-ddBCMA were available and presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.
• All six patients responded per IMWG criteria.
• Four patients achieved a stringent complete response.
• The therapy was well tolerated, with CAR-T related toxicities resolving rapidly.

The phase I trial for ACLX-001 is due to commence in the second half of 2021.