A Phase 2, Open-Label, Multicenter Study of the Safety and Efficacy of TAK-007 in Adult Patients with...

In relapsed/refractory large B-cell lymphoma (LBCL), chimeric antigen receptor (CAR)-natural killer (NK) cell therapies offer potential advantages over CAR-T-cell therapies, including off-the-shelf availability and scalable manufacturing. We performed a phase 2 study of single-dose TAK-007, a cryopreserved, cord blood-derived, off-the-shelf CD19 CAR-NK cell therapy, in 26 heavily pre-treated patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). Adverse events were manageable, with limited grade 1-2 cytokine release syndrome (11.5%). Overall response rate with TAK-007 800 x106 CD19 CAR+ viable NK cells (n=14) was 60.9% (95% CI: 38.5-80.3). Median progression-free survival was 2.0 months (95% CI: 0.99-3.58) in LBCL (n=10) and 5.6 months (95% CI: 1.05-8.57) in indolent NHL (n=7) expansion cohorts. Deep molecular responses, including ctDNA-negative responses, were achieved. Not all TAK-007 products elicited clinical responses; single cell RNA-sequencing showed NK proliferating and NK-CD56dim cell enrichment in TAK-007 products eliciting/not eliciting responses, respectively, which could inform product selection.