NKX101 Demonstrates Early Activity in Relapsed/Refractory AML


Treatment with NKX101 led to a best composite complete response rate of 67% in patients with relapsed/refractory acute myeloid leukemia, according to updated data from a dose-expansion cohort of an ongoing phase 1 trial.

Carlos Bachier, MD

Carlos Bachier, MD

Treatment with NKX101 led to a best composite complete response (CR) rate of 67% (n = 4/6) in patients with relapsed/refractory acute myeloid leukemia (AML), according to updated data from a dose-expansion cohort of an ongoing phase 1 trial (NCT04623944).

In this cohort, NKX101 was administered 3 times a week at a dose of 1.5 billion cells/dose following lymphodepletion with fludarabine and cytarabine. Specifically, 50% of patients (n = 3/6) experienced a CR with hematologic recovery, and 1 patient had a CR with incomplete hematologic recovery (CRi).

Additionally, two of the 4 complete responses were negative for measurable residual disease (MRD). One patient with an MRD-positive CR underwent allogeneic transplant and remained in CR at 4 months. Another patient with CR was without detectable disease by flow cytometry.

“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 at Methodist Hospital in San Antonio, Texas, said in a press release. “NKX101 following lymphodepletion with fludarabine and [cytarabine] had encouraging antitumor 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.”

NKX101 is an allogeneic, cryopreserved, off-the-shelf immune therapy that uses donor-derived natural killer (NK) cells engineered to target NKG2D ligands on cancer cells.

In the phase 1 trial, eligible patients received either fludarabine and cyclophosphamide lymphodepletion or fludarabine and cytarabine lymphodepletion followed by NKX101. NKX101 was dosed at 100 million, 300 million, 1 billion or 1.5 billion NK cells three times in the 3-dose regimen, or 150 million or 1.5 billion NK cells twice in the 2-dose regimen.

As of June 10, 2023, 36 patients with relapsed/refractory AML were enrolled in the phase 1 trial, compared with 17 at the previous update of April 21, 2022.

Thirty patients received NKX101 following lymphodepletion with fludarabine and cyclophosphamide in the dose-finding and a separate dose-expansion cohort.

Most patients had poor-risk disease (n = 17/30; 57%) and were heavily pretreated, with a median of 2 prior lines of therapy (range, 1-12). Additionally, 90% (n = 27/30) of patients received prior venetoclax (Venclexta). Among patients who received the highest doses of NKX101, the CR/CRi rate was 22% (n = 4/18) and the CR rate was 17% (n = 3/18).

Another expansion cohort enrolled 6 patients who received lymphodepletion with fludarabine and cytarabine followed by 3 weekly doses of NKX101 at 1.5 billion cells/dose. This cohort included patients with poor risk disease (n = 5/6; 83%), early relapse after allogeneic hematopoietic cell transplant, and chemotherapy-refractory disease. The patients in this cohort were also heavily pretreated, receiving a median of 2 prior lines of therapy (range, 1-3) and all having been previously exposed to venetoclax-containing regimens.

“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 of Nkarta, said. “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 fludarabine [and cytarabine].”

Regarding safety, NKX101 was well tolerated. No dose-limiting toxicities occurred, and the safety profile of NKX101 was consistent with both lymphodepletion regimens.

In the 30 patients enrolled in the dose-finding cohort, grade 3 or greater adverse effects (AEs) included thrombocytopenia (60%), anemia (53%), neutropenia (43%), febrile neutropenia (27%), white blood cell count decrease (17%), leukocytosis (13%), pneumonia (10%), hypoxia (13%), fatigue (10%), and hypotension (10%).

Expected CAR T-cell therapy–like events included grade 1/2 infusion reactions (12%), grade 1/2 cytokine release syndrome (CRS; 12%), and 1 case of grade 2 immune effector cell–associated neurotoxicity syndrome (ICANS).

In the expansion cohort using fludarabine and cytarabine, there were no reports of CRS, ICANS, or graft-vs-host disease. In this cohort, grade 3 or greater AEs included anemia (50%), febrile neutropenia (50%), neutropenia (50%), thrombocytopenia (33%), lymphocyte count decrease (33%), white blood cell count disease (33%), and sepsis (50%).

The company expects to enroll between 12 and 20 additional patients to the expansion cohort using the fludarabine and cytarabine lymphodepletion regimen from phase 1 and provide an update in the first half of 2024.


Nkarta updates clinical progress of CAR-NK cell therapy NKX101 for patients with relapsed or refractory acute myeloid leukemia. News release. Nkarta Inc. June 27, 2023. Accessed June 27, 2023. https://ir.nkartatx.com/news-releases/news-release-details/nkarta-updates-clinical-progress-car-nk-cell-therapy-nkx101

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