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

Brief Title

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

Official Title

A Phase 1 Study of NKX019, a CD19 Chimeric Antigen Receptor Natural Killer (CAR NK) Cell Therapy, in Subjects With B-cell Malignancies

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.

Study Phase

Phase 1

Study Type

Interventional

Primary Outcome

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

Secondary Outcome

 Assessment of NKX019 half-life

Condition

Lymphoma, Non-Hodgkin

Intervention

NKX019

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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Biological

Estimated Enrollment

Start Date

August 20, 2021

Completion Date

December 2038

Primary Completion Date

December 2023

Eligibility Criteria

        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

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

David Shook, MD, +1 415-651-5080, [email protected]

Location Countries

Australia

Location Countries

Australia

Administrative Informations

NCT ID

NCT05020678

Organization ID

NKX019-101

Responsible Party

Sponsor

Study Sponsor

Nkarta Inc.

Study Sponsor

David Shook, MD, Study Director, Nkarta Inc.

Verification Date

January 2023