Fate Therapeutics Receives FDA Clearance of IND for FT819 in B-Cell Malignancies

The FDA has cleared an investigational new drug application for the first-of-its-kind, off-the-shelf CAR T-cell product FT819, which targets CD19-positive malignancies.

The FDA has cleared an investigational new drug application (IND) for the first-of-its-kind, off-the-shelf CAR T-cell product FT819, which targets CD19-positive malignancies, according to an announcement from Fate Therapeutics, the drug’s co-developer.1

The biopharmaceutical company plans to evaluate the product as a treatment for patients with relapsed/refractory B-cell malignancies, including chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), and non-Hodgkin lymphoma (NHL).

"The clearance of our IND application for FT819 is a ground-breaking milestone in the field of cell-based cancer immunotherapy. Our unique ability to produce CAR T cells from a clonal master engineered iPSC line creates a pathway for more patients to gain timely access to therapies with curative potential,” Scott Wolchko, president and chief executive officer of Fate Therapeutics, stated in a recent press release.

As the first CAR-T cell therapy created from cell clonal master-induced pluripotent stem cell (iPSC) line, FT819 can be mass-produced and delivered off the shelf to offer broader access to the treatment. This CAR T-cell product was also developed to improve the safety and efficacy of this modality, and address limitations linked with the patient- and donor-derived products that are currently available, according to Fate Therapeutics.

The treatment is the result of a collaborative effort between a group of investigators led by Michael Sadelain, MD, PhD, the director of the Center for Cell Engineering and head of Gene Expression and Gene Transfer Laboratory at from Memorial Sloan Kettering Cancer Center and Fate Therapeutics.

“Four years ago, we first set out under our partnership with Memorial Sloan Kettering led by Dr. Michel Sadelain to improve on the revolutionary success of patient-derived CAR T-cell therapy and bring an off-the-shelf paradigm to patients, and we are very excited to advance FT819 into clinical development,” Wolchko added.

In the development of the product, investigators incorporated 1XX CAR signaling domain in an effort to extend T-cell effector function without inducing exhaustion. Additionally, CAR transgene was inserted directly into the T-cell receptor alpha constant (TRAC) locus, which is believed to encourage uniform CAR expression and amplify T-cell potency. Notably, the therapy was also designed to result in the complete bi-allelic disruption of T-cell receptor expression to prevent graft-versus-host disease (GVHD), a notable complication that is known to occur with allogeneic T-cell therapy.

Preclinical data presented during the 2020 AACR Virtual Meeting II showed that FT819 possessed a uniform product profile of ≥95% CAR+, TCR-, CD45+, CD7+, and CD3+ with most of the CD8 T cells expressing CD8β.2 The global gene expression profile of the product showcased high similarity to primary CD19-targeted CAR T cells, thus solidifying its identity as a T lymphocyte, according to the study authors.

Functional assessment revealed strong antigen-specific cytolytic activity against leukemia and lymphoma cell lines (P = .0004) with the product. On-target, off-tumor cytolysis of CD19-positive B cells were confirmed in mixed lymphocyte reaction assay. Moreover, FT819 proved to be unable to produce a GVH response in a co-culture assay with anti-TCR crosslinking antibodies. Furthermore, FT819 was shown to control tumor growth (P = .0003 at day 21) in disseminated leukemia xenograft mouse studies. The product also showed sustained bone marrow localization for 45 days following treatment in a systemic administered leukemia model.

“Collectively, these studies demonstrate that FT819 is a potent, homogenous CAR19 T-cell product candidate and can be potentially effectively used off-the-shelf in the treatment of B-cell malignancies,” the investigators concluded.

In a planned multicenter phase 1 trial, investigators will identify the maximum-tolerated dose of FT819, as well as the clinical activity and safety of the product in 297 patients with B-cell malignancies, including CLL, ALL, and NHL. Notably, each indication will enroll independently and 3 doses of FT819 will be examined: a single dose of the product (regimen A), a single dose of FT819 in combination with IL-2 cytokine support (regimen 2), and 3 fractionated doses of FT819 (regimen C). Dose-expansion cohorts comprised of up to 15 patients for each indication and regimen can be used to further examine the clinical activity of the CAR T-cell product.


  1. Fate Therapeutics Announces FDA Clearance of IND Application for First-ever iPSC-derived CAR T-Cell Therapy. News release. Fate Therapeutics. July 9, 2020. Accessed July 9, 2020. https://bit.ly/39eDFIm.
  2. Mandal M, Clarke R, Stegen SV, et al. FT819 path to IND: First-of-kind off-the-shelf CAR19 T-cell for B cell malignancies. Presented at: AACR Virtual Annual Meeting II; June 22-24, 2020. Poster 3245. https://bit.ly/2ZOd01R.