TAK-007 CAR-NK cell therapy for R/R B-cell NHL: A phase II study

Results from a phase II, open-label, multicenter study (NCT05020015), evaluating single-dose TAK-007, a cryopreserved, allogeneic, cord blood-derived, off-the-shelf CD19-directed chimeric antigen receptor (CAR)-natural killer (NK) cell therapy expressing interleukin-15 (IL-15), in heavily pretreated patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL), were published in Blood Cancer Discovery by Darrah et al. The primary objectives were to determine the safety, tolerability, and recommended phase II dose (RP2D).

Key data: The RP2D was 800 × 10⁶ CD19-directed CAR+ viable NK cells. In the safety population (N = 26), Grade ≥3 TEAEs occurred in 92.3%, most commonly neutropenia (73.1%), leukopenia (50.0%), anemia (38.5%), and thrombocytopenia (38.5%). No dose-limiting toxicities (DLTs), graft-versus-host disease (GvHD), or TAK-007-related immune effector cell-associated neurotoxicity syndrome (ICANS) occurred; TAK-007-related cytokine release syndrome (CRS) was limited to Grade 1–2 (11.5%). Across the 800 × 10⁶ dose escalation and expansion cohorts, the overall response rate (ORR) was 60.9% (complete response [CR], 34.7%; partial response [PR], 26.1%); the ORR was 50.0% in large B-cell lymphoma (LBCL) and 77.8% in indolent NHL (iNHL). Median progression-free survival (PFS) was 2.0 months in LBCL and 5.6 months in iNHL. Circulating tumor DNA (ctDNA)-negative responses were achieved in five patients.

Key learning: TAK-007 demonstrated a manageable safety profile and preliminary activity in heavily pretreated R/R B-cell NHL; further studies are needed to optimize outcomes by refining manufacturing protocols.