FT596, a CD19-directed chimeric antigen receptor (CAR) natural killer (NK) cell therapy, was well tolerated in patients with relapsed or refractory B-cell lymphoma as a monotherapy or in combination with rituximab, according to results from a phase 1, first-in-human trial.
The study, led by Armin Ghobadi, MD, of Washington University School of Medicine in St. Louis, Missouri, was published in The Lancet.
“FT596 was well tolerated as monotherapy or with rituximab and induced deep and durable responses in patients with indolent and aggressive lymphomas,” the investigators wrote.
Investigators also identified the recommended phase 2 dose of FT596, an induced pluripotent stem cell-derived CAR-NK cell therapy, as 1.8 × 10⁹ cells administered in three doses per cycle.
The trial, conducted at nine sites across the United States, enrolled 86 patients between March 19, 2020, and January 12, 2023. All patients had received at least one prior line of therapy, with a median of four previous treatments (range, 1–11). Of these, 33 patients (38%) had been treated with a CAR-T.
Participants were assigned to one of two regimens, with 18 patients receiving FT596 (regimen a) and the remainder receiving FT596 in combination with rituximab (regimen b).
The maximum tolerated dose was not reached in the study. Cytokine release syndrome was observed in one patient (6%) in the regimen a group (maximum grade 1) and nine patients (13%) on regimen b, including six cases of grade 1 and three cases of grade 2. No neurotoxicity was reported by the investigators.
“In patients with follicular lymphoma, FT596 has shown comparable efficacy to the three FDA-approved CAR-T cell therapies, but with significantly reduced toxicity,” Dr. Ghobadi said in a press release published by the Washington University School of Medicine. “For patients with large B-cell lymphoma who undergo FDA-approved CAR-T cell therapy, approximately 60% experience a relapse. These patients have very limited treatment options, and most survive only a few months. This study demonstrates that nearly half of these patients could achieve another complete or partial remission with FT596, representing a significant improvement.”
Funding was provided by Fate Therapeutics.
Reference
Ghobadi A, Bachanova V, Patel K, et al. Induced pluripotent stem-cell-derived CD19-directed chimeric antigen receptor natural killer cells in B-cell lymphoma: a phase 1, first-in-human trial. Lancet. 2025;405(10473):127-136. doi:10.1016/S0140-6736(24)02462-0
