FDA clears IND application for stem cell-derived CAR-T targeting CD19-positive tumors
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The FDA cleared an investigational new drug application for FT819, a chimeric antigen receptor T-cell therapy for the treatment of CD19-positive tumors, according to a press release from the agent’s manufacturer.
FT819 (Fate Therapeutics) is allogeneic CAR T-cell therapy that targets the CD19 protein on the surface of cancer cells.
The investigational cell therapy is derived from a clonal master induced pluripotent stem cell (iPSC) line and contains several innovations designed to improve the efficacy and safety of CAR T-cell therapy, according to the manufacturer.
The approval allows Fate to move forward with a multicenter phase 1 trial to determine the safety, efficacy and maximum tolerated dose of FT819 for adults with B-cell malignancies, including chronic lymphoblastic leukemia, acute lymphoblastic leukemia and non-Hodgkin lymphoma.
The trial will enroll up to 279 patients and will evaluate three dosing regimens.
“The clearance of our IND application for FT819 is a groundbreaking milestone in the field of cell-based cancer immunotherapy,” Scott Wolchko, president and CEO of Fate Therapeutics, said in the press release. “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.”
The FDA based the IND clearance on preclinical data, presented during this year’s virtual American Association for Cancer Research Annual Meeting, that showed FT819 demonstrated antitumor effects comparable to healthy autologous CAR T cells in mouse models of lymphoblastic leukemia.
The novel features of FT819 were developed under a collaborative agreement with Memorial Sloan Kettering Cancer Center and led by Michel Sadelain, MD, PhD, director of the Center for Cell Engineering and head of the Gene Expression and Gene Transfer Laboratory at the cancer center. These innovations include:
- use of a clonal master iPSC line as the starting cell source that enables mass production of CAR T cells and off-the-shelf delivery for broader patient access;
- a novel 1XX CAR signaling domain that has been shown to extend T-cell effector function without eliciting T-cell exhaustion;
- insertion of the CAR transgene directly into the T-cell receptor-alpha constant (TRAC) locus, which has been shown to promote uniform CAR expression and enhanced T-cell potency; and
- complete biallelic disruption of T-cell receptor expression to prevent graft-versus-host disease.
“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 said.
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