FT516

P1, N=72, Terminated, Fate Therapeutics | Trial completion date: May 2039 --> Oct 2023 | Active, not recruiting --> Terminated | Trial primary completion date: May 2024 --> Oct 2023; The study was terminated by the Sponsor.

P1, N=72, Active, not recruiting, Fate Therapeutics | Recruiting --> Active, not recruiting | N=234 --> 72

P1, N=234, Recruiting, Fate Therapeutics | N=72 --> 234 | Trial completion date: May 2026 --> May 2039 | Trial primary completion date: Jul 2021 --> May 2024

Primary objectives of the study are to determine the recommended Phase II dose of FT516 in combination with rituximab (R) or obinutuzumab (G) in R/R BCL and to evaluate safety and tolerability in patients (pts) with R/R BCL...The ongoing dose-escalation stage assesses FT516 for up to 2 cycles, each consisting of 3 days of conditioning chemotherapy (cyclophosphamide [CY] 500 mg/m 2 and fludarabine [FLU] 30 mg/m 2 ), a single-dose of R (375 mg/m 2 ), and 3 weekly doses of FT516 (30-900 million cells per dose) each with IL-2 support (6 MIU)...Following dose escalation, further investigation of safety and efficacy will be conducted as follows: FT516 + R or G following FLU/CY in pts with R/R diffuse large B-cell lymphoma (DLBCL) or R/R follicular lymphoma (FL) who have not received prior CAR T-cell therapy; FT516 + R following FLU/CY in pts with R/R BCL who have previously received CAR T-cell therapy; and FT516 + R following bendamustine... As of 07 July 2021, 13 pts (2 at 30 million cells per dose, 4 at 90 million cells per dose, and 7 at 300 million cells per dose) were enrolled and had at least 3 months of follow-up or discontinued. Pts had DLBCL, including transformed indolent (7 pts), high-grade BCL (HGBCL, 3 pts), low-grade FL (2 pts), or marginal zone lymphoma (1 pt), and received a median of 3 prior lines of therapy and a median of 2 prior lines containing CD20-targeted therapy. Ten of 13 pts received both planned treatment cycles (6 doses of FT516); 3 pts discontinued after a single cycle due to disease progression.

Primary objectives of the study are to determine the recommended Phase II dose of FT516 in combination with rituximab (R) or obinutuzumab (G) in R/R BCL and to evaluate safety and tolerability in patients (pts) with R/R BCL...The ongoing dose-escalation stage assesses FT516 for up to 2 cycles, each consisting of 3 days of conditioning chemotherapy (cyclophosphamide [CY] 500 mg/m 2 and fludarabine [FLU] 30 mg/m 2 ), a single-dose of R (375 mg/m 2 ), and 3 weekly doses of FT516 (30-900 million cells per dose) each with IL-2 support (6 MIU)...Following dose escalation, further investigation of safety and efficacy will be conducted as follows: FT516 + R or G following FLU/CY in pts with R/R diffuse large B-cell lymphoma (DLBCL) or R/R follicular lymphoma (FL) who have not received prior CAR T-cell therapy; FT516 + R following FLU/CY in pts with R/R BCL who have previously received CAR T-cell therapy; and FT516 + R following bendamustine... As of 07 July 2021, 13 pts (2 at 30 million cells per dose, 4 at 90 million cells per dose, and 7 at 300 million cells per dose) were enrolled and had at least 3 months of follow-up or discontinued. Pts had DLBCL, including transformed indolent (7 pts), high-grade BCL (HGBCL, 3 pts), low-grade FL (2 pts), or marginal zone lymphoma (1 pt), and received a median of 3 prior lines of therapy and a median of 2 prior lines containing CD20-targeted therapy. Ten of 13 pts received both planned treatment cycles (6 doses of FT516); 3 pts discontinued after a single cycle due to disease progression.

To overcome these barriers, we developed a robust genetic editing and manufacturing platform for the uniform engineering and expansion of high-quality NK cells derived from induced pluripotent stem cells (iPSCs)...Previously, we reported on our ability to effectively target multiple myeloma with our FT538 program (the iNK defined below), now FDA approved for clinical trials...Collectively, our results show that utilizing the iNK cell platform to uniformly express hnCD16 and IL15RF combined with complete CD38 KO is an effective strategy to promote effective ADCC against CD38+ cells in the absence of fratricide, and that CD38 KO reprograms NK cells for higher oxidative metabolic fitness for improved persistence and anti-tumor function. Furthermore, we have generated proof-of-concept data supporting triple gene-modified iNK cells combined with dara as a novel AML immunotherapy.