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

Sponsor

Nkarta Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05020678

Collaborator

(none)

Enrollment

Locations

Arm

202.3

Anticipated Duration (Months)

8.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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)

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Non-Hodgkin B-cell Acute Lymphoblastic Leukemia Large B-cell Lymphoma Mantle Cell Lymphoma Indolent Lymphoma Waldenstrom Macroglobulinemia Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Aggressive Lymphoma Large-cell Lymphoma	Biological: NKX019	Phase 1

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. 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 Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Aug 20, 2021

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Jul 1, 2038

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NKX019 - CAR NK cell therapy 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.	Biological: NKX019 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 (2 × 10^6/kg for patients < 50 kg) administered as 3 weekly doses. Part 2 will use the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of NKX019 as determined in Part 1.

Arm

Intervention/Treatment

Experimental: NKX019 - CAR NK cell therapy

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.

Biological: NKX019

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 (2 × 10^6/kg for patients < 50 kg) administered as 3 weekly doses. Part 2 will use the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of NKX019 as determined in Part 1.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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
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 [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

General:

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-directed therapy must have disease that remains CD19+
Have measurable disease
Have received ≥2 lines of therapy except subjects with MCL 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
Adequate organ function
White blood cell count of ≤20 × 109/L
Platelet count ≥30,000/uL

Exclusion Criteria:

• Disease related:

Burkitt Lymphoma, primary 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 LBCL expansion cohort who must have received prior CD19 directed 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
2	University of Chicago	Chicago	Illinois	United States	60637
3	The Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
4	Institute of Haematology, Royal Prince Alfred Hospital	Camperdown	New South Wales	Australia	2050
5	St. Vincent's Hospital	Sydney	New South Wales	Australia	2010
6	Royal Brisbane and Woman's Hospital	Brisbane	Queensland	Australia	4029
7	Peter MacCallum Cancer Center	Melbourne	Victoria	Australia	3000