A Phase 1 Study of NKX101, an Activating Chimeric Receptor Natural Killer Cell Therapy, in Subjects With Hematological Malignancies or Dysplasias
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Nkarta, Inc.
- 入组人数
- 61
- 试验地点
- 8
- 主要终点
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
- •Signed informed consent
- •Agree to use an effective barrier method of birth control
排除标准
- •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
- •Pregnant or lactating female
研究组 & 干预措施
NKX101 - CAR NK cell therapy
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.
干预措施: NKX101 - CAR NK cell therapy (Biological)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
时间窗: 30 days after last dose of NKX101
Incidence, nature, and severity of treatment related adverse events will be evaluated. An adverse event is any unfavorable and unintended sign including clinically significant abnormal laboratory findings, symptom or disease.
Response rate to NKX101 (for Part 2)
时间窗: 28 days from first dose of NKX101
Responses will be assessed per modified ELN criteria and will include complete and partial remission with and without varying degrees of hematologic recovery
次要结局
- Assessment of NKX101 half-life(28 days from first dose of NKX101)
- NKX101 duration of persistence(Followed up to 2 years after last dose of NKX101)
- Evaluation of host immune response against NKX101(Followed up to 2 years after last dose of NKX101)
- Response rate to NKX101(Primary assessment: 28 days after first dose of NKX101 followed up to 2 years after last dose of NKX101)