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

Nkarta, Inc.

Status and phase: Active, not recruiting; Phase 1

Conditions: Relapsed/Refractory AML; MDS; AML, Adult; Refractory Myelodysplastic Syndromes

Treatments: Biological: NKX101 - CAR NK cell therapy

Study type: Interventional

Funder types: Industry

Identifiers

NCT04623944

NKX101-101

Details and patient eligibility

About

This is a single-arm, open-label, multi-center, Phase 1 study to determine safety and tolerability of an experimental therapy called NKX101 (allogeneic CAR NK cells targeting NKG2D ligands) in patients with relapsed/refractory AML or intermediate, high and very high risk relapsed/refractory MDS.

Full description

This is a dose-finding study of NKX101 and will be conducted in 2 parts:

Part 1: dose finding with two dosing regimens, utilizing modified "3+3" enrollment schema.

Part 2: dose expansion to further evaluate safety and tolerability, cellular kinetics, pharmacodynamics and anti-tumor response in expansion cohorts of patients with either AML or MDS.

Enrollment: 61 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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61 participants in 1 patient group

NKX101 - CAR NK cell therapy

Experimental group

Description:

All subjects in Part 1 will receive lymphodepletion with fludarabine/cyclophosphamide followed by 3 or 2 (Regimen A or B, respectively) weekly doses of NKX101. Subjects in Part 2 will receive lymphodepletion with either fludarabine/cyclophosphamide or fludarabine/cytarabine (ara-C), or if the optional arm is opened, lymphodepletion with fludarabine/cyclophosphamide and decitabine, followed by 3 weekly doses of NKX101. Part 2: unrelated off-the-shelf donor derived NKX101 will be used.

Treatment:

Biological: NKX101 - CAR NK cell therapy