A Phase 2, Open-Label, Multicenter Study of the Safety and Efficacy of TAK-007 in Adult Patients with Relapsed/Refractory B-cell Non-Hodgkin Lymphoma
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.
Authors
- Reem Karmali (ORCID: https://orcid.org/0000-0003-0984-4376)
- Varsha Sundaresan
- Matthew McKinney (ORCID: https://orcid.org/0000-0002-2979-4882)
- Monalisa Ghosh (ORCID: https://orcid.org/0000-0003-2260-8212)
- Jennifer N. Saultz (ORCID: https://orcid.org/0000-0003-0024-9466)
- Indumathy Varadarajan (ORCID: https://orcid.org/0000-0001-8737-4053)
- Ajeetha Ramachandran
- Usama Gergis (ORCID: https://orcid.org/0000-0003-0656-7385)
- Leopold Sellner (ORCID: https://orcid.org/0000-0002-7893-401X)
- Justin Darrah (ORCID: https://orcid.org/0000-0002-6557-4027)
- Girish Bende
- Kevin Galinsky (ORCID: https://orcid.org/0000-0003-0311-4938)
- Amitkumar Mehta
- Andrew Krueger (ORCID: https://orcid.org/0000-0001-5817-0262)
- Bradley Hupf (ORCID: https://orcid.org/0009-0007-4180-9091)
- Siddha Kasar (ORCID: https://orcid.org/0009-0001-8633-4292)
Institutions
- Cedars-Sinai Medical Center (US)
- University of Alabama at Birmingham Hospital (US)
- Thomas Jefferson University (US)
- Oregon Health & Science University (US)
- University of Michigan (US)
- Northwestern Memorial Hospital (US)
- Duke Medical Center (US)
- Takeda (United States) (US)
- Takeda (Japan) (JP)
- University of Virginia (US)
Publication Details
- Journal
- Blood Cancer Discovery
- Published
- 2026-04-17
- DOI
- https://doi.org/10.1158/2643-3230.bcd-25-0323-a
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Gilead Sciences
- BeiGene
- Incyte
- Genentech