Nektar and Partners Reveal Phase 2 NKTR-255 Study Results for Radiation-Induced Lymphopenia in NSCLC at SITC Meeting

Nektar Therapeutics, in collaboration with The University of Texas MD Anderson Cancer Center, presented compelling Phase 2 study results at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC). This study, focusing on NKTR-255, a polymer-conjugated IL-15 agonist, aimed to address radiation-induced lymphopenia in patients with locally advanced non-small cell lung cancer (NSCLC) who had undergone concurrent chemoradiation.

NKTR-255 is engineered to stimulate the proliferation and activation of natural killer (NK) and CD8+ T-cells, enhancing the body's immune response. This agent is under investigation for its potential synergy with cellular therapies and immune checkpoint inhibitors. Previous research has established its capability to amplify various immune cells and promote lymphocyte trafficking.

The interim analysis from the RESCUE trial showed promising outcomes. Patients treated with NKTR-255 following chemoradiation and in combination with durvalumab exhibited significant lymphocyte recovery compared to historical controls. Notably, the eight-week absolute lymphocyte count (ALC) was markedly improved in these patients versus those who received chemoradiation alone or chemoradiation combined with durvalumab without NKTR-255.

Dr. Steven H. Lin from MD Anderson emphasized the importance of these findings, noting that radiation-induced lymphopenia commonly worsens overall survival in solid tumors like lung cancer. The rapid restoration of lymphocyte counts with NKTR-255 post-chemoradiation suggests potential prognostic benefits and enhanced survival rates for NSCLC patients.

Mary Tagliaferri of Nektar Therapeutics highlighted the broader implications of NKTR-255's efficacy. The consistent results across studies underline NKTR-255's potential to improve clinical outcomes in both hematologic malignancies and solid tumors.

The ongoing Phase 2 single-arm study at MD Anderson administers NKTR-255 intravenously every four weeks in combination with durvalumab for up to a year. The primary focus is on safety and the normalization of ALC at the eight-week mark post-treatment initiation. Secondary goals include evaluating progression-free survival and overall survival rates. The trial (NCT05632809) is continuing to recruit and treat patients.

Key points from the presentation included:
- The combination of NKTR-255 and durvalumab post-chemoradiation demonstrated safety and tolerability, with adverse events consistent with previous trials.
- Interim pharmacodynamic data showed a statistically significant improvement in the eight-week ALC with NKTR-255 post-chemoradiation and in combination with durvalumab.
- NKTR-255 administration also increased markers of NK cell proliferation and activation.

About NKTR-255:
NKTR-255 targets the IL-15 pathway to activate the body's innate and adaptive immunity. By engaging the IL-15 receptor complex, it aims to enhance NK cell populations and foster long-term immunological memory, potentially improving the anti-tumor immune response.

Apart from its combination with CAR T cell therapies, NKTR-255 is undergoing evaluation in a Phase 1 trial sponsored by AbelZeta, assessing a tumor-infiltrating lymphocyte therapy in anti-PD1 resistant metastatic NSCLC (NCT05676749). The JAVELIN Bladder Medley study, sponsored by Merck KGaA, is also investigating NKTR-255 in combination with avelumab for treating advanced or metastatic urothelial carcinoma (NCT05327530).

Nektar Therapeutics is a clinical-stage biotechnology company, headquartered in San Francisco, focused on developing treatments for autoimmune and chronic inflammatory diseases. Their lead product, rezpegaldesleukin (REZPEG, or NKTR-358), is a novel regulatory T cell stimulator under evaluation in Phase 2b trials for atopic dermatitis and alopecia areata. The company's pipeline includes a preclinical candidate, NKTR-0165, a bivalent tumor necrosis factor receptor type II agonist antibody. Alongside partners, Nektar is also advancing NKTR-255 through various clinical trials to boost the immune system's cancer-fighting capabilities.