NKX019, Intravenous Allogeneic Chimeric Antigen Receptor Natural Killer Cells (CAR NK), in Adults With B-cell Cancers

NCT05020678 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: NKX019-101
• Study Type: interventional
• Target: 150
• Locations: 2 countries
• Sites: 6

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)

Conditions

Lymphoma, Non-Hodgkin; B-cell Acute Lymphoblastic Leukemia; Large-cell Lymphoma; Large B-cell Lymphoma; Mantle Cell Lymphoma; Indolent Lymphoma; Waldenstrom Macroglobulinemia; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Aggressive Lymphoma

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

Outcome Measures

Primary Outcomes (3)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  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.

  30 days after last dose of NKX019

• Proportion of subjects experiencing dose-limiting toxicities of NKX019

  DLTs are defined as adverse events attributable to NKX019 treatment that occur during Cycle 1 and meet protocol-specified criteria

  28 days from first dose of NKX019

• Objective response rate to NKX019 in Part 2

  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.

  Primary assessment: 28 days after the first dose of NKX019 followed up to 2 years after the last dose of NKX019]

Secondary Outcomes (4)

• 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

• 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

Study Arms (1)

NKX019 - CAR NK cell therapy

EXPERIMENTAL

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.

Biological: NKX019

Interventions

NKX019 BIOLOGICAL

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.

NKX019 - CAR NK cell therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nkarta, Inc.: lead

Study Sites (6)

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Institute of Haematology, Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

St. Vincent's Hospital

Sydney, New South Wales, 2010, Australia

Location

Royal Brisbane and Woman's Hospital

Brisbane, Queensland, 4029, Australia

Location

Peter MacCallum Cancer Center

Melbourne, Victoria, 3000, Australia

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Burkitt Lymphoma; Lymphoma, Mantle-Cell; Waldenstrom Macroglobulinemia; Leukemia, Lymphocytic, Chronic, B-Cell; Dendritic Cell Sarcoma, Interdigitating

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Histiocytic Disorders, Malignant; Histiocytosis

Study Officials

• David Shook, MD

  Nkarta, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2021
• First Posted: August 25, 2021
• Study Start: August 20, 2021
• Primary Completion: March 31, 2025
• Study Completion (Estimated): December 1, 2038
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4); US (2)