Fate presents interim data from dose-escalation stage of Phase 1 study of FT819

Fate Therapeutics presented interim clinical data from the dose-escalation stage of its ongoing Phase 1 study of FT819 for patients with relapsed / refractory B-cell lymphoma at the 64th American Society of Hematology Annual Meeting and Exposition. The landmark trial is the first-ever clinical investigation of a T-cell product candidate manufactured from a clonal master induced pluripotent stem cell line, a renewable cell source that enables mass production of engineered T-cell therapies with greater product consistency, off-the-shelf availability, and broader patient accessibility. FT819 incorporates several first-of-kind features including the integration of a novel CD19-targeted 1XX chimeric antigen receptor construct into the T-cell receptor alpha constant locus, which is intended to promote uniform CAR expression, enhance T-cell potency, and prevent graft-versus-host disease. The multi-center Phase 1 clinical trial of FT819 is designed to assess its safety and clinical activity in adult patients with r/r BCL and to determine the recommended Phase 2 dose and schedule. As of the September 8, 2022 data cutoff date, 10 patients with aggressive large B-cell lymphoma have been treated with FT819, including 8 patients in Regimen A with a single dose of FT819 and 2 patients in Regimen B with three fractionated doses of FT819 on Days 1, 3, and 5. Patients received standard conditioning chemotherapy consisting of cyclophosphamide at 500 mg/m2 and fludarabine at 30 mg/m2 for 3 days prior to the initiation of each regimen. Patients were heavily pre-treated having received a median of 4 prior lines of therapy, including 7 of 10 patients having previously received autologous CD19-targeted CAR T-cell therapy. As of the September 8, 2022 data cutoff date, an additional 5 patients with r/r BCL have been treated with FT819. One patient with Grade 3a follicular lymphoma treated in Regimen A with a single dose of FT819 at 180 million cells achieved a complete response at Day 30. Four patients with Richter’s Transformation did not respond to therapy at Day 30. No dose-limiting toxicities, and no Grade 3 or greater FT819-related adverse events or serious AEs, were observed. Of the 15 patients treated in Regimens A and B, three patients experienced Grade 2 cytokine release syndrome characterized by fever, hypotension, and hypoxia, which events resolved with single-dose tocilizumab and supportive care. No treatment-emergent AEs of any grade of immune effector cell-associated neurotoxicity syndrome or graft-versus-host disease were reported by investigators. The FT819 treatment regimen was well tolerated. Grade 3 or greater TEAEs not related to FT819 primarily included hematologic cytopenias associated with conditioning chemotherapy. There were no study discontinuations or deaths due to TEAEs other than one patient with stable disease who died on Day 38 due to sepsis not considered related to FT819 by the study investigator. The ASH presentation featured a patient case study demonstrating the potential to safely administer more than one treatment cycle of FT819 and reinduce an objective response following disease progression. The 73 year-old female with DLBCL had previously been treated with 4 prior lines of therapy, including commercial autologous CD19-targeted CAR T-cell therapy with best response of PR, and was refractory to last prior therapy. The patient received a first treatment cycle with a single dose of FT819 at 90 million cells, achieving a PR at Day 30 with 94% reduction in size of target lesions. Continued follow-up through November 8, 2022 was significant for disease progression on Day 72, for which the patient received a second treatment cycle with a single dose of FT819 at 180 million cells on Day 134 with consent from the U.S. Food and Drug Administration and achieved a PR at Day 163 with 61% reduction in size of target lesions. Both treatment cycles were well tolerated with no Grade 3 or greater FT819-related AEs or serious AEs, no reports of any grade of CRS, ICANS, or GvHD, and no evidence of new or worsening toxicity with the second treatment cycle. Following each treatment cycle, FT819 was detected in the peripheral blood with peak level at Day 4 in Cycle 1 and at Day 8 in Cycle 2, with maximum peak level at Day 8 in Cycle 2 at 8,152 transgene copies/undefined DNA. Dose escalation is currently ongoing in Regimen A as a single dose of FT819 at 360 million cells and in Regimen B with three fractionated doses at 60 million cells per dose. The Company has also amended the FT819 study protocol to allow for the use of bendamustine at 90 mg/m2 for 2 days as an alternative to Cy / Flu conditioning chemotherapy.