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.

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