Aggressive Lymphoma, B-cell Acute Lymphoblastic Leukemia, Chronic Lymphocytic Leukemia, Indolent Lymphoma, Large B-cell Lymphoma, Large-cell Lymphoma, Lymphoma, Non-Hodgkin, Mantle Cell Lymphoma, Small Lymphocytic Lymphoma, Waldenstrom Macroglobulinemia
Conditions
Keywords
CD19, CAR, Allogeneic, Natural killer, ACR, NKX019, IL15, Interleukin 15, NK cell, Cell Therapy, Immunotherapy, Adoptive cell therapy, r/r NHL, r/r B-ALL, r/r MCL, r/r IL, r/r WM, r/r CLL, r/r SLL, Aggressive lymphoma, Indolent lymphoma, LCL
Brief summary
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)
Detailed description
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.
Interventions
BIOLOGICALNKX019
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 (6 × 10\^6/kg for patients \< 50 kg) administered as 3 weekly doses. Part 2 (dose expansion cohorts) will use the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of NKX019 as determined in Part 1.
Sponsors
Nkarta, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
General: 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
Exclusion criteria
• 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Objective response rate to NKX019 in Part 2 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 in Part 1 | 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. |
Countries
Australia, United States
Contacts
STUDY_DIRECTORDavid Shook, MD
Nkarta, Inc.
Outcome results
None listed