Inclusion Criteria:

• General:
  • ECOG performance status ≤2
• Disease related:
  • For AML subjects:
    • Previously treated relapsed/refractory AML, including subjects with MRD+ disease
    • Received at most 3 lines of previous anti-leukemia therapy
    • 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
    • White blood cell count of ≤25 × 10^9/L
    • 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
    • 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
    • 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:
    • Intermediate-, high-, or very high-risk MDS
    • Previously treated relapsed/refractory MDS
    • Received at least 1 and at most 3 lines of previous standard anti-MDS therapy
    • 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
    • For group receiving lymphodepletion with fludarabine/cyclophosphamide +/- decitabine and NKX101: Additional subjects who have relapsed following HCT may be enrolled.
• Adequate Organ Function
• Platelet count ≥30,000/uL (platelet transfusions acceptable)
• Other:
• • Signed informed consent
  • Agree to use an effective barrier method of birth control

Exclusion Criteria:

• Disease related:
  • 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)
  • Evidence of leukemic meningitis or known active central nervous system disease
  • 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
  • Use of any anti-AML/MDS chemotherapeutic or targeted small molecule drug within protocol specified window prior to the first dose of NKX101
  • Presence of residual non-hematologic toxicity from prior therapies that has not resolved to ≤ Grade 1
  • Any hematopoietic cell transplantation within 16 weeks
• Other comorbid conditions and concomitant medications prohibited as per study protocol
• Other:
• • Pregnant or lactating female