FT819

P1, N=32, Recruiting, Fate Therapeutics

P1, N=396, Recruiting, Fate Therapeutics | N=297 --> 396

Conditioning chemotherapy consists of 3 consecutive days of fludarabine (30 mg/m2) and cyclophosphamide (500 mg/m2) prior to the first dose of FT819. FT819 is the first-ever, off-the-shelf, iPSC-derived CAR T-cell therapy to be tested in clinical trials. The ongoing Phase I study is designed to assess multiple dosing regimens across a broad range of B-cell malignancies. Interim clinical data, including safety, tolerability, and initial anti-tumor activity from the ongoing Phase I dose-escalation study of FT819, will be presented at the conference.

A multi-center Phase 1 study of FT819 is currently ongoing for the treatment of B-cell malignancies. Key Words: cancer immunotherapy, cell therapy, CAR-T, CD19, allogeneic, induced pluripotent stem cell, iPSC, clonal master iPSC line, engineered, off-the-shelf, cGMP, production, manufacturing, FT819

P1, N=297, Recruiting, Fate Therapeutics | Not yet recruiting --> Recruiting | Trial completion date: Dec 2037 --> Sep 2039 | Initiation date: Dec 2020 --> Jul 2021 | Trial primary completion date: Dec 2022 --> Sep 2024

We recently developed FT819, a first-of-kind off-the-shelf chimeric antigen receptor (CAR)-T cell therapy derived from a renewable master iPSC line engineered to uniformly express a novel CD19 1XX-CAR driven by the endogenous (TCR) promoter at the T-cell receptor α constant (TRAC) locus...Our preliminary data validate the potential of engineering multiple modalities at desired loci of clonal iPSCs to enable the creation of functionally enhanced CAR-T cells. Ongoing work is focused on extending these studies into disease specific models, as well as further investigating other TCE and TCL candidates for the development of next-generation iPSC derived CAR-T therapy with better efficacy and safety profiles.

P1, N=297, Not yet recruiting, Fate Therapeutics

Lympho-conditioning will consist of three consecutive days of fludarabine and cyclophosphamide administered prior to the first dose of FT819...Key exclusion criteria include ongoing immunosuppression such as systemic GVHD therapy, prior allograft organ transplant, active central nervous system involvement of disease, and known allergy to FT819 components. The trial is expected to begin patient recruitment in 2020.

Ongoing in vivo studies will assess long-term survival and avoidance of GvH disease. Collectively, these studies demonstrate that FT819 is a potent, consistent and uniform CAR19 T cell product and can be effectively and safely used off-the-shelf in the treatment of B cell malignancies with an original Phase 1 clinical trial planned in 2020.

The use of induced pluripotent stem cells (iPSCs) to derive immune effector cells offers distinct advantages for immune therapy over existing patient- or donor- derived platforms, not only in terms of scalable manufacturing and precision genetic engineering at the clonal level, but also in allowing the generation and combinational use of multiple effector cell types each with distinct characteristics. FT596 also shows enhanced clearance of CD19+CD20+ Burkitts lymphoma cell line RAJI when used in combination with rituximab (p=0.0002 vs rituximab alone). Collectively, these studies suggest a compounded anti-tumor effect can be achieved utilizing the inherent properties of engineered CAR-iNK cells together with therapeutic antibody combined with engineered CAR-iT cells which will be highlighted in this presentation.