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

Phase 1

Active, not recruiting

• Conditions: Lymphoma, Non-Hodgkin; Large B-cell Lymphoma; Mantle Cell Lymphoma; B-cell Acute Lymphoblastic Leukemia; Indolent Lymphoma; Small Lymphocytic Lymphoma; Large-cell Lymphoma; Waldenstrom Macroglobulinemia; Aggressive Lymphoma; Chronic Lymphocytic Leukemia
• Interventions: Biological: NKX019

• Registration Number: NCT05020678
• Lead Sponsor: Nkarta, Inc.

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 Timeline

• Study Start: 2021-08-20
• Study First Submitted: 2021-08-20
• Study First Submitted QC: 2021-08-20
• Study First Posted: 2021-08-25
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-20
• Last Update Posted: 2024-12-24
• Primary Completion: 2025-03
• Study Completion: 2038-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 150

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
NKX019 - CAR NK cell therapy	NKX019	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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

Trial Locations

Locations (6)

Colorado Blood Cancer Institute; 🇺🇸 Denver, Colorado, United States

The Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

Institute of Haematology, Royal Prince Alfred Hospital; 🇦🇺 Camperdown, New South Wales, Australia

St. Vincent's Hospital; 🇦🇺 Sydney, New South Wales, Australia

Royal Brisbane and Woman's Hospital; 🇦🇺 Brisbane, Queensland, Australia

Peter MacCallum Cancer Center; 🇦🇺 Melbourne, Victoria, Australia