NKX019, Intravenous Allogeneic Chimeric Antigen Receptor Natural Killer Cells (CAR NK), in Adults With B-cell Cancers
A Phase 1 Study of NKX019, a CD19 Chimeric Antigen Receptor Natural Killer (CAR NK) Cell Therapy, in Subjects With B-cell Malignancies
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)
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.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Assessment of NKX019 half-life
Study Arms / Comparison Groups
NKX019 - CAR NK cell therapy
Description: 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.
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
August 20, 2021
Primary Completion Date
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
18 Years - N/A
Accepts Healthy Volunteers
David Shook, MD, +1 415-651-5080, [email protected]
David Shook, MD, Study Director, Nkarta Inc.