Carlos Bachier, MD, Sarah Cannon Center for Blood Cancer, Nashville, TN, outlines the design of a Phase I trial (NCT04623944) of NKX101, an allogeneic CAR-NK cell therapy, in relapsed/refractory (R/R) acute myeloid leukemia (AML) or higher-risk myelodysplastic syndrome (MDS). CAR-T cell therapy has shown little benefit in myeloid malignancies, resulting from a lack of AML-specific targets and a hostile microenvironment. Investigations into alternative options for this patient population have identified allogeneic haplomatched NK-cells as having clinical activity in AML, while causing minimal cytokine release syndrome and neurotoxicity. NKX101 cells are engineered to have enhanced anti-AML cytolytic activity, which has been demonstrated preclinically. The 3+3 dose-escalation and dose-expansion study will evaluate the safety, tolerability, and anti-tumor activity of NKX101 in AML/MDS and identify the recommended Phase II dose. Degree of HLA match will also be explored for its impact on safety and efficacy. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.