NKX019, Intravenous Allogeneic Chimeric Antigen Receptor Natural Killer Cells (CAR NK), in Adults With B-cell Cancers
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)
|Condition or Disease||Intervention/Treatment||Phase|
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. 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.
Arms and Interventions
|Experimental: 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.
NKX019 is an investigational allogeneic CAR NK product targeting CD19 on cells. The starting dose of NKX019 in Part 1 is 3 × 10^8 NK cells (2 × 10^6/kg for patients < 50 kg) administered as 3 weekly doses. Part 2 will use the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of NKX019 as determined in Part 1.
Primary Outcome Measures
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [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 [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
Secondary Outcome Measures
- Assessment of NKX019 half-life [Time Frame: 28 days from first dose of NKX019]
Time required for 50% reduction from maximum amount of circulating NKX019
- NKX019 duration of persistence [Followed up to 2 years after last dose of NKX019]
Testing NKX019 in peripheral blood every 3 months after dosing to determine persistence
- Evaluation of host immune response against NKX019 [Followed up to 2 years after last dose of NKX019]
Serum samples will be measured for antibodies against NKX019
- Objective response rate to NKX019 [Primary assessment: 28 days after first dose of NKX019 followed up to 2 years after 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.
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-directed therapy must have disease that remains CD19+
Have measurable disease
Have received ≥2 lines of therapy except subjects with MCL 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
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
Adequate organ function
White blood cell count of ≤20 × 109/L
Platelet count ≥30,000/uL
• Disease related:
Burkitt Lymphoma, primary 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 LBCL expansion cohort who must have received prior CD19 directed 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
Contacts and Locations
|1||Colorado Blood Cancer Institute||Denver||Colorado||United States||80218|
|2||University of Chicago||Chicago||Illinois||United States||60637|
|3||The Cleveland Clinic Foundation||Cleveland||Ohio||United States||44195|
|4||Institute of Haematology, Royal Prince Alfred Hospital||Camperdown||New South Wales||Australia||2050|
|5||St. Vincent's Hospital||Sydney||New South Wales||Australia||2010|
|6||Royal Brisbane and Woman's Hospital||Brisbane||Queensland||Australia||4029|
|7||Peter MacCallum Cancer Center||Melbourne||Victoria||Australia||3000|
Sponsors and Collaborators
- Nkarta Inc.
- Study Director: David Shook, MD, Nkarta Inc.
Study Documents (Full-Text)None provided.