avipendekin pegol (NKTR-255)

Single-cell RNA sequencing and mass cytometry revealed upregulated apoptosis and transforming growth factor-β (TGF-β) signaling as the potential mechanisms of response/resistance to NK cell therapy in vivo. Our findings highlight potential application of chemokine-enhanced NK tumor infiltration in combination with an IL-15 agonist as a novel approach to effective treatment of OSA.

P1, N=28, Active, not recruiting, Fred Hutchinson Cancer Center | Recruiting --> Active, not recruiting

In this phase 2, randomized, double-blind, placebo-controlled, multicenter study of NKTR-255 versus placebo following CD19 CAR T-cell therapy, eligible patients with R/R LBCL were treated with one of two FDA-approved CAR T-cell products, axicabtagene ciloleucel (axi-cel) or lisocabtagene maraleucel (liso-cel). NKTR-255 was well-tolerated, safe, and augmented CR6 for LBCL patients. Based on the findings, additional confirmatory studies with NKTR-255 as adjuvant treatment to CAR T-cell, including other cellular therapies, are warranted (ClinicalTrials.gov number NCT05664217).

P2, N=256, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Trial completion date: Jan 2025 --> Jul 2026 | Trial primary completion date: Jan 2025 --> Jun 2025

P2/3, N=15, Terminated, Nektar Therapeutics | N=400 --> 15 | Trial completion date: Jan 2029 --> Aug 2024 | Recruiting --> Terminated | Trial primary completion date: Jan 2027 --> May 2024; Sponsor decided to end the study

P1, N=24, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2024 --> Jun 2025

NKTR-255, a polymer-conjugated recombinant human interleukin-15 agonist, significantly stimulated NK cell proliferation and expansion and further enhanced the in vitro cytotoxic activity and in vivo anti-tumor efficacy of anti-MCAM-CAR-NK cells against NB. Our preclinical studies demonstrate that ex vivo expanded and modified anti-MCAM-CAR-NK cells alone and/or in combination with NKTR-255 are promising novel alternative therapeutic approaches to targeting MCAMhigh malignant NB.

Our preclinical studies demonstrate that immunotherapy via the innate immune system by combining tumor-targeting CAR-NK cells with an IL-15 agonist and a CD47 blockade is a promising novel therapeutic approach to targeting MCAMhigh malignant metastatic ES.

P2, N=256, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Recruiting --> Active, not recruiting

The increase in chemokines was associated with decreases in absolute lymphocyte counts and CD8+ CAR T-cells in blood and ten-fold increases in CSF CAR-T cells, suggesting lymphocyte trafficking to tissue. Combining NKTR-255 with CAR19-22 was safe, feasible and associated with high rates of durable responses (NCT03233854).

P1/2, N=25, Completed, Nektar Therapeutics | Phase classification: P1b/2 --> P1/2

P1, N=20, Recruiting, AbelZeta, Inc. | Not yet recruiting --> Recruiting