High Dose NK Cell Therapy Shows Efficacy in AML

NKX101 (Nkarta), an allogeneic, NKG2D ligand-targeting natural killer (NK) cell therapy has shown signs of efficacy and was well-tolerated in patients with relapsed or refractory acute myeloid leukemia (AML).

“Patients with relapsed or refractory AML have few treatment options, and novel approaches are urgently needed. Traditional chemotherapy is often unable to drive deep remissions in this setting, and many patients cannot tolerate it,” Carlos Bachier, MD, Medical Director of Research and Cellular Therapy, Sarah Cannon Transplant & Cellular Therapy Program, Methodist Hospital, San Antonio, Texas, said in a statement. “NKX101 following lymphodepletion with fludarabine and Ara-C had encouraging anti-tumor activity in a small number of patients with difficult to treat relapsed/refractory AML. This activity, together with its tolerable safety profile, merits further study of NKX101.”

The study has enrolled 36 patients as of June 10, 2023, to be treated with NKX101 after lymphodepletion with fludarabine and cyclophosphamide across the dose finding and dose expansion cohorts, most of which (n = 17, 57%) of patients had poor risk disease. Participants had 2 median lines of therapy (range, 1-12) and 27 (90%) had been treated with venetoclax.

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In the dose expansion cohort, 4 of 6 patients receiving 3 weekly doses of NKX101 at 1.5 billion cells achieved complete response (CR) or incomplete CR (CRi; 67%) and 3 achieved a CR with hematologic recovery. Two of the 4 reported CRs were MRD (measurable residual disease) negative. One patient with MRD positive CR remains in CR 4 months after allogeneic hematopoietic stem cell transplant. In patients that received the highest doses of NKX101 in the dose finding cohort, (3 weekly doses at 1 billion or 1.5 billion cells per dose), 4 of 18 achieved CR/CRi (22%) and 3 achieved a CR with hematologic recovery CR (17%). There were no CRs at the lower doses.

NKX101 was well tolerated with no dose-limiting toxicities observed across cohorts and Nkarta stated that its safety profile is positively differentiated from those of many cell therapies. Toxicities included 5 (12%) infusion reactions of at least grade 2, 5 (12%) cases of2 cytokine release syndrome (CRS) at least grade 2, 1 case of grade 2 immune effector cell-associated neurotoxicity syndrome, and no graft-versus-host disease. The most common higher-grade adverse events were myelosuppression.

Nkarta expects to enroll 12 to 20 additional patients in the expansion cohort, with more data to come in the first half of 2024. The company may also change protocols to standardize criteria for retreatment and consolidation and simplify study logistics.

“NK cell therapy has long held promise for patients with AML, and these latest results highlight our continued progress towards delivering on that promise with NKX101,” David R. Shook, MD,Chief Medical Officer, Nkarta, added. “While these data are early and in a small number of patients, the response rate exceeds the rate observed with even the latest approved agents and highlights the potential advantages of lymphodepletion using Flu/Ara-C.”

REFERENCE

Nkarta Updates Clinical Progress Of CAR-NK cell therapy NKX101 for patients with relapsed or refractory acute myeloid leukemia. News release. Nkarta. June 27, 2023.