FDA clears FT538, the first CRISPR-edited, iPSC-derived cell therapy, for investigation as a new drug in AML and MM

On May 20, 2020, the U.S. Food & Drug Administration (FDA) cleared FT538, the first CRISPR-edited, induced pluripotent stem cell (iPSC)-derived cell therapy, for clinical investigation as a new monotherapy for patients with acute myeloid leukemia (AML) and as a combination therapy with daratumumab, a CD38-directed monoclonal antibody therapy, for the treatment of multiple myeloma (MM).¹

Key features¹

FT538

• An off-the-shelf natural killer (NK) cell cancer immunotherapy, derived from a clonal master iPSC line
• Engineered with three functional components to enhance innate immunity:
  • A novel high-affinity, non-cleavable CD16 Fc receptor that improves antibody-dependent cellular cytotoxicity by enhancing NK cells to recognize, bind, and kill antibody-coated cancer cells
  • An IL-15/IL-15 receptor complex that promotes NK cell survival and persistence, as well as inducing trans-activation of endogenous NK cells and CD8 T cells
  • Elimination of CD38 expression, which enhances innate effector function, including granzyme and perforin levels, and resistance to oxidative stress, as well as preventing anti-CD38 antibody-mediated NK cell death

Study Design^1,2

• Phase I, multi-center, dose-escalation trial to determine the maximum tolerated dose (MTD) of three once-weekly doses of FT538 in up to 105 adult patients
• Four dose cohorts of 100M cells, 300M cells, 900M cells, or 1.5B cells per dose
• Designed to assess two treatment regimens:
  • As a monotherapy in patients with relapsed/refractory AML
  • In combination with daratumumab in patients with relapsed/refractory MM who have failed at least two lines of therapy
• There is also potential for initiation of a third treatment regimen in combination with elotuzumab, an FDA-approved anti-SLAMF7 monoclonal antibody, in patients with relapsed/refractory MM who have failed at least two lines of therapy

The therapy aims to provide a robust population of NK cells that are resistant to depletion when used in combination with anti-CD38 antibodies and thus improve outcomes for patients with MM and AML.