Allogeneic CAR-NK Therapy TAK-007 Achieves Responses in R/R B-NHL

Takeda’s TAK-007, an allogeneic cord blood-derived CD19-directed chimeric antigen receptor natural killer (CAR-NK) cell therapy, has demonstrated safety and efficacy in a phase 2 clinical trial (NCT05020015) evaluating the therapy for the treatment of patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL) or indolent nonHodgkin lymphoma (iNHL).¹ The data were presented by Justin M. Darrah, MD, codirector of the Lymphoma Program and director of the CAR T-cell Therapy program at Cedars-Sinai, at the 66th American Society of Hematology (ASH) Annual Meeting, held December 7-10, 2024, in San Diego, California.

The 26 patients treated in the trial included 3 patients with LBCL who were treated at the study’s low dose (200M cells), 14 patients with LBCL who were treated at the study’s high dose (800M cells), and 9 patients with iNHL who were treated at the high dose. The overall response rate (ORR) for the total group of 26 patients was 53.8%, with the complete response rate (CRR) being 30.8% and the partial response rate (PRR) being 23.1%. For patients with LBCL who received the high dose, the ORR was 50.0%, with a 21.4% CRR and a 28.6% PRR. For patients with iNHL, the ORR was 77.8%, with a CRR of 55.6% and a PRR of 22.2%. For the 35% of patients in the trial who received the high dose of TAK-007 and had previously been treated with CD19 CAR T-cell therapy, the ORR was 42.9%. For the patients in the trial who received the high dose of TAK-007 and had not previously been treated with CD19 CAR T-cell therapy, the ORR was 68.8%.

Darrah pointed out that the responses seen in the trial were not particularly durable, however, with a median duration of response (DOR) of 2.6 months observed for the patients with LBCL and a DOR of 4.9 months observed for the patients with iNHL. He also noted that responses to TAK-007 appeared to be unrelated to CD19 antigen densities and that higher exposures to TAK-007 were positively correlated with the probability of a response.

With regard to safety, there were no dose-limiting toxicities, no cases of graft versus host disease (GvHD), and no cases of TAK-007-related immune effector cell-associated neurotoxicity syndrome (ICANS). TAK-007-related cytokine release syndrome was reported in 3 patients, with 1 case being grade 2 and the other cases being grade 1. One patient experienced an infusion-related reaction. Darrah pointed out that 81% of patients had grade 2 or higher cytopenia at baseline. Nonhematologic treatment-emergent adverse events (TEAEs) were grade 1 to 2 in 77% of cases. Nausea, which occurred in 15 patients (58%) and fatigue (14 patients, 54%) constituted the most common nonhematologic TEAEs.

Furthermore, 24 patients (92%) experienced grade 3 or higher TEAEs, with the most common of these being neutropenia (19 patients, 73%) and leukopenia (13 patients, 50%). Twenty patients (77%) in the trial experienced serious TEAEs, but in 14 of these patients (54%) the serious TEAEs were deemed unrelated to TAK-007 and the lymphodepleting chemotherapy. Seven patients died from their underlying disease.

The ages of the patients treated in the trial ranged from 38 years to 83 years (median 54). The group included 18 men (69%). With regard to race, 23 patients (88%) treated in the trial were white, 1 patient was black (4%), 1 patient (4%) was Asian, and 1 patient was listed as being multiple races (4%). One patient’s ethnicity was reported as Hispanic or Latino. The number of prior lines of therapy received by the treated patients ranged from 2 to 11 (median, 5). Eleven patients (42%) had previously received antiCD19 therapies and 9 patients (35%) had previously received CAR-T therapy.

“In summary, TAK-007 is an allogeneic off-the-shelf CD19-directed CAR NK cell therapy,” Darrah concluded his presentation.¹ “It offers potential clinical and operational advantages versus our standard autologous CAR T-cell therapy options. The 800M dose demonstrated early efficacy and a favorable safety profile, with low rates of infusion related reactions and CRS and no cases of ICANS or GvHD... We think that it's possible that administration of more than 1 dose of TAK-007 at the 800M dose may result in higher efficacy and better durability of response and may be an area for future exploration.”

For more coverage of ASH 2024, click here.

REFERENCE
1. Darrah JM, Varadarajan I, Mehta A, et al. Efficacy and safety of TAK-007, cord blood-derived CD19 CAR-NK Cells, in adult patients with relapsed/refractory (R/R) B-cell non-Hodgkin Lymphoma (NHL). Presented at: ASH 2024 Annual Meeting. December 7-10, 2024; San Diego, CA. Abstract 95