A Phase 1 Study of NKX019, a CD19 Chimeric Antigen Receptor Natural Killer (CAR NK) Cell Therapy, in Subjects With B-cell Malignancies
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
- 150
- 试验地点
- 10
- 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 the safety and tolerability of an experimental therapy called NKX019 (allogeneic CAR NK cells targeting CD19) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) or B cell acute lymphoblastic leukemia (B-ALL)
详细描述
This is a dose-finding study of NKX019 and will be conducted in 2 parts:
Part 1: dose finding utilizing a "3+3" enrollment schema and safety lead-in to confirm dose for NKX019 in combination with rituximab expansion cohorts (as applicable) Part 2: dose expansion to further evaluate safety and tolerability, cellular kinetics, pharmacodynamics and anti-tumor response in expansion cohorts of patients with large B cell lymphoma (LBCL), mantle cell lymphoma (MCL), indolent lymphoma (IL), Waldenström macroglobulinemia (WM), CLL/ small lymphocytic lymphoma (SLL), and B-ALL.
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
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- •Disease Related:
- •Have a histologically or cytologically confirmed diagnosis of r/r B cell NHL or CLL or B-ALL as defined by WHO 2016 classification
- •Subjects who received prior CD19/CD20-directed therapy must have disease that remains CD19+ and/or CD20+ respectively
- •Have measurable disease
- •Have received ≥2 lines of therapy except subjects with MCL, CAR T Naïve cohorts and WM, who must have received at least 1 prior line of therapy
- •Have received a combination of an anti CD20 monoclonal antibody and cytotoxic chemotherapy for subjects with NHL
- •Received:
- •BTKi for subjects with MCL, CLL/SLL, WM, and other indications where a BTKi is approved
- •Venetoclax for subjects with CLL/SLL
- •Tyrosine kinase inhibitor for subjects with Philadelphia chromosome (Ph+) B-ALL
- •Not responded or relapsed within 12 months of completion of their prior line of therapy, with the exception of a newly diagnosed Richter's transformation of CLL/SLL or other transformation of an indolent lymphoma, including from WM
- •Subjects must not have evidence of rapidly progressive disease that would preclude subject from completing at least 1 cycle of treatment.
- •Adequate organ function
- •White blood cell count of ≤20 × 109/L
- •Platelet count ≥30,000/uL
排除标准
- •Disease related:
- •Burkitt Lymphoma, primary central nervous system (CNS) lymphoma, Richter's transformation to Hodgkin lymphoma
- •Subjects with WM who underwent plasmapheresis <35 days prior to the first dose of NKX019
- •Subjects with NHL with any evidence of active CNS malignancy
- •Subjects with B-ALL who have extramedullary disease (EMD)
- •Subjects with any prior cellular therapy except subjects enrolling in selected cohorts who must have received prior CAR T therapy, recent HCT, or complications from HCT
- •Recent use of any cancer-directed therapy within protocol specified window prior to the first dose of NKX019
- •Residual toxicities ≥Grade 2 due to prior therapy
- •Other comorbid conditions and concomitant medications prohibited as per study protocol
- •Pregnant or lactating female
研究组 & 干预措施
NKX019 - CAR NK cell therapy
All subjects will receive fludarabine/cyclophosphamide lymphodepletion followed by 3 weekly doses of NKX019 on Day 0, 7, and 14 of a 28-day cycle. Combination cohorts (if opened) will additionally receive rituximab with each cycle.
干预措施: NKX019 (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 NKX019
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.
Proportion of subjects experiencing dose-limiting toxicities of NKX019
时间窗: 28 days from first dose of NKX019
DLTs are defined as adverse events attributable to NKX019 treatment that occur during Cycle 1 and meet protocol-specified criteria
Objective response rate to NKX019 in Part 2
时间窗: Primary assessment: 28 days after the first dose of NKX019 followed up to 2 years after the last dose of NKX019]
Percentage of subjects with complete and partial response. Response to treatment will be assessed based on: Lugano classification with LYRIC refinement for subjects with NHL (except CLL/SLL and WM); 2018 iwCLL guidelines for subjects with CLL/SLL; Version 1.2020 NCCN for subjects with B-ALL; consensus criteria from the 6th International Workshop on Waldenström Macroglobulinemia for subjects with WM.
次要结局
- Evaluation of host immune response against NKX019(Followed up to 2 years after last dose of NKX019)
- Objective response rate to NKX019 in Part 1(Primary assessment: 28 days after first dose of NKX019 followed up to 2 years after last dose of NKX019)
- Assessment of NKX019 half-life(Time Frame: 28 days from first dose of NKX019)
- NKX019 duration of persistence(Followed up to 2 years after last dose of NKX019)