NKX101, Intravenous Allogeneic CAR NK Cells, in Adults With AML or MDS

Inclusion Criteria:

General:

ECOG performance status ≤2

Disease related:

For AML subjects:

1. Previously treated relapsed/refractory AML, including subjects with MRD+ disease
2. Received at most 3 lines of previous anti-leukemia therapy
3. For subjects with targetable fms-like tyrosine kinase 3 (FLT3)-mutated or isocitrate dehydrogenase (IDH)1/2 mutated disease, subjects must have received at least 1 prior respective targeted therapy and may receive up to 4 lines of prior therapy
4. White blood cell count of ≤25 × 10^9/L
5. For groups receiving NKX101 after lymphodepletion with fludarabine/cyclophosphamide +/- decitabine: Disease localized to the bone marrow, as evidenced by ≤ 5% peripheral blasts and no evidence of extramedullary disease
6. For groups receiving NKX101 after lymphodepletion with fludarabine/ cyclophosphamide +/- decitabine, group receiving NKX101 after lymphodepletion with fludarabine/ara-C: Additional subjects with specifically high-risk genetic mutations may be enrolled. High risk genetic mutation per ELN 2022 should be evaluated as per local assay and discussed with the Sponsor prior to study entry
7. For groups receiving NKX101 after lymphodepletion with fludarabine/cyclophosphamide +/- decitabine, group receiving NKX101 after lymphodepletion with fludarabine/ara-C: Additional subjects who have relapsed following HCT may be enrolled.

For MDS subjects:

1. Intermediate-, high-, or very high-risk MDS
2. Previously treated relapsed/refractory MDS
3. Received at least 1 and at most 3 lines of previous standard anti-MDS therapy
4. For groups receiving NKX101 after lymphodepletion with fludarabine/ cyclophosphamide +/- decitabine: Additional subjects with specifically high-risk disease may be enrolled. High-risk genetic mutation should be evaluated as per local assay
5. For group receiving lymphodepletion with fludarabine/cyclophosphamide +/- decitabine and NKX101: Additional subjects who have relapsed following HCT may be enrolled.
6. Adequate Organ Function
7. Platelet count ≥30,000/uL (platelet transfusions acceptable)

Other:

1. Signed informed consent
2. Agree to use an effective barrier method of birth control

Exclusion Criteria:

Disease related:

1. Acute promyelocytic leukemia with t(15;17) (q22;q12); or abnormal promyelocytic leukemia/retinoic acid receptor alpha (APML-RARA) and AML arising from chronic myelomonocytic leukemia (CMML)
2. Evidence of leukemic meningitis or known active central nervous system disease
3. Peripheral leukocytosis with ≥ 20,000 blasts/μL or other evidence of rapidly progressive disease that would preclude subject from completing at least 1 cycle of treatment
4. Use of any anti-AML/MDS chemotherapeutic or targeted small molecule drug within protocol specified window prior to the first dose of NKX101
5. Presence of residual non-hematologic toxicity from prior therapies that has not resolved to ≤ Grade 1
6. Any hematopoietic cell transplantation within 16 weeks
7. Other comorbid conditions and concomitant medications prohibited as per study protocol

Other:

Pregnant or lactating female