Clinical trial of NKX019, cell therapy for lupus nephritis, opens

Ntrust-1 to assess safety, efficacy of 3 cycles of CAR natural killer cell therapy

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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Patient screening is underway in a U.S.-based clinical trial of NKX019, an investigational natural killer (NK) cell therapy for people with treatment-resistant lupus nephritis, a serious complication of lupus, its developer, Nkarta, announced.

The trial, called Ntrust-1, is a multicenter and open-label study to assess the safety, efficacy, and clinical activity of NKX019 in up to 12 patients with refractory lupus nephritis. Study results are expected to be released in 2025, Nkarta reported in a company press release.

Ntrust-1’s launch follows clearance received from the U.S. Food and Drug Administration (FDA) in October to begin testing the therapy in people with lupus nephritis. NKX019 also is under testing in people with B-cell blood cancers.

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Limited treatment options among reasons for clinical trials in lupus nephritis

An autoimmune disease, lupus is caused by the production of self-reactive antibodies produced by immune B-cells that mistakenly attack healthy tissues.

Lupus nephritis is a severe disease complication that damages and impairs the function of the kidneys, and which currently has limited treatment options.

Cell-based therapies that help other immune system cells target and destroy self-reactive B-cells are of particular interest in treating autoimmune diseases. These include CAR T-cell therapies, which use immune T-cells engineered in the lab to have a chimeric antigen receptor (CAR) designed to target and attack other cells with specific protein markers, including B-cells.

NKX019 is a CAR cell therapy using immune cells known as NK cells, as natural killer cells are considered less likely to trigger an unwanted immune response than T-cells. The therapy involves collecting NK cells from a healthy donor and modifying them in the lab with a CAR targeting CD19, a protein found on the surface of B-cells. The modified cells also contain a version of interleukin-15, an immune signaling protein that helps in sustaining therapeutic activity, on their surface.

NK cells can be collected from one donor and modified for use in many patients, which is referred to as an allogeneic approach. These cells can also be expanded in large batches, being ready to use as needed, rather than being produced on demand for each patient, Nkarta reported.

“NKX019 is unencumbered by many of the safety, infrastructure and logistical challenges associated with existing cell therapy approaches,” said Paul J. Hastings, Nkarta’s president and CEO. “Many people living with lupus are historically underserved, and our aim is to develop treatments that are broadly accessible and easier to tolerate and administer.”

In Ntrust-1, after a round of chemotherapy to clear immune cells that are triggering the disease and to make room for the new CAR NK cells, patients will be treated with three cycles of NKX019 (at 1 or 1.5 billion cells), weekly for three weeks. Additional cycles may be given to restore a response.

The FDA also approved Nkarta’s request to start a clinical trial testing NKX019 in people with other autoimmune conditions, including systemic sclerosis, ANCA-associated vasculitis, and  idiopathic inflammatory myopathy. The company is planning to launch a trial, to be called Ntrust-2, testing NKX019 in patients with these disorders.

“The initiation of Ntrust-1 in lupus nephritis and the … clearance for three additional indications are critical milestones in our mission to improve the accessibility and safety of cell therapy,” Hastings said.