An RMAT designation granted to FT516 is supported by data from a phase 1 trial of FT516 in patients with diffuse large B-cell lymphoma.
The FDA has granted a regenerative medicine advanced therapy designation to FT516 for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to a press release by Fate Therapeutics, Inc.
FT516 is an investigational, off-the-shelf natural killer cell cancer immunotherapy. It is derived from a clonal master induced pluripotent stem cell line that is engineered to express a novel high affinity 158V, a non-cleavable CD16 FC receptor.
The designation is supported by data from a phase 1 dose-escalation efficacy data presented at the 63rdAmerican Society of Hematology Annual Meeting and Exposition. The phase 1 study (NCT04023071) has an estimated enrollment of 72 participants and an estimated study completion date of May 2026. The primary end point is the rate of incidence of subjects with dose limiting toxicities. Secondary end points include objective response rate and FT516 pharmacokinetic data.
During the study, patients were randomized to receive either FT516 monotherapy or FT516 monotherapy in combination with monoclonal antibodies. Patients with relapsed/refractory BCL received up to 2 cycles of therapy. Each cycle consisted of 3 days of conditioning chemotherapy, followed by a single-dose of rituximab, and 3 weekly doses of FT516 with IL-2 cytokine support.
The median number of prior lines of therapy received by patients in the dose-escalation stage was 3.5, with a median of 3 prior lines of therapy containing CD20-targeted therapy. At the data cutoff date of October 18, 2021, 4 patients in the second dose cohort of 90 million cells per dose, 7 patients in the third dose cohort of 300 million cells per dose, and 7 patients in the fourth dose cohort of 900 million cells per dose were evaluable for safety and efficacy (n = 18). Of those patients, 10 were CD19- targeted chimeric antigen receptor (CAR) T-cell therapy naïve. Three patients in the fourth dose cohort were refractory to CAR T-cell therapy.
In CAR T naïve patients with CAR T naïve aggressive BCL (n = 5), the ORR was 80%, with a complete response rate of 40%. At a median follow-up of 8.3 months (range, 4.6-9.9), 60% of patients had an ongoing response. In patients with CAR T naïve indolent BCL (n = 5), the ORR was 80%, with a complete response rate of 60%. At a median follow-up of 9.9 months (range, 3.7-13.2), 60% of participants were experiencing an ongoing response.
In patients with aggressive BCL who received a prior CAR T-cell therapy (n = 8), the ORR was 38%, with a complete response of 38%. At a median follow-up of 6.5 months (range, 4.6-8.3), 25% of patients were experiencing an ongoing response.
In terms of safety, all grade TEAEs occurred in 75% of patients in the 90 m dose cohort (n = 4). Grade 3 or higher TEAEs occurred in 50% of patients in this cohort. In the 300 m dose cohort, the rate of all grade TEAEs was 29% and the rate of grade 3 or higher TEAEs was 14%. In the 900 M dose cohort, TEAEs occurred in 30% of the population, with 20% of patients experiencing a grade 3 or higher AE.
“We continue to be highly encouraged by the differentiated therapeutic profile of FT516 as an off-the-shelf NK cell therapy administered in the outpatient setting, and its potential to deliver deep and durable responses for patients with advanced B-cell lymphomas, including those that have received prior autologous CAR T-cell therapy,” said Wayne Chu, MD, senior vice president of Clinical Development of Fate Therapeutics in a press release.
“The RMAT designation for the treatment of relapsed/refractory DLBCL reflects the positive clinical data we have observed with FT516 in the dose-escalation stage of our Phase 1 study, and it is an important milestone for the Company that recognizes the unique potential of off-the-shelf, iPSC-derived, NK cell cancer immunotherapy. We look forward to working closely with the FDA to accelerate the development of FT516 in this area of significant unmet medical need with the goal of expanding the reach of transformative cell therapies.”
In order to participate in the study, patients must be 18 years of age or older and have measurable disease. Patients with an ECOG performance status of 2 or higher, evidence of insufficient organ function, have received an allograft organ transplant, known central nervous system metastases, clinically significant cardiovascular disease, or known HIV infection are not eligible to participate.