On November 7, 2024 Nektar Therapeutics (Nasdaq: NKTR) and collaborators at The University of Texas MD Anderson Cancer Center reported late-breaking results from a Phase 2 study evaluating NKTR-255 for the treatment of radiation induced lymphopenia after concurrent chemoradiation in locally advanced non-small cell lung cancer (NSCLC) patients at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting (Press release, Nektar Therapeutics, NOV 7, 2024, View Source [SID1234647982]).

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NKTR-255 is a novel polymer-conjugated IL-15 agonist, designed to activate, proliferate and expand natural killer (NK) and CD8+ T-cells, as well as to promote the survival and expansion of memory CD8+ T cells. NKTR-255 is currently being evaluated in combination with cellular therapies and immune checkpoint inhibitors. Previous pre-clinical and clinical studies have shown that NKTR-255 can proliferate a range of immune cells and augment lymphocyte trafficking.1,2,3

The results from the preplanned interim analysis from the REStoring lymphoCytes Using NKTR-255 after chemoradiothErapy in solid tumors (RESCUE) trial suggest that NKTR-255 effectively reversed radiation induced lymphopenia in patients with locally advanced NSCLC receiving consolidation therapy with durvalumab. Interim pharmacodynamic data demonstrated statistically significant superiority of the eight-week absolute lymphocyte count (ALC) with NKTR-255 post chemoradiation and in combination with durvalumab versus non-contemporaneous control groups who received either chemoradiation alone or chemoradiation in combination with durvalumab.

"Radiation induced lymphopenia is common after chemoradiation therapy and is associated with worse overall survival in multiple solid tumors including lung cancer." said Steven H. Lin, MD, PhD, Professor of Radiation Oncology at MD Anderson. "These interim results showing that NKTR-255 can rapidly restore absolute lymphocyte counts post chemoradiation suggest that NKTR-255 has the potential to confer prognostic benefits and enhanced survival in patients with locally advanced NSCLC."

"These results, combined with the body of evidence previously reported with NKTR-255 in combination with cell therapy, highlight NKTR-255’s potential to enhance clinical benefit in both hematologic malignancies and solid tumors" said Mary Tagliaferri, MD, Senior Vice President and Chief Medical Officer at Nektar.

The Phase 2 single-arm study conducted by MD Anderson is evaluating NKTR-255 (3µg/kg IV) following concurrent chemoradiation and in combination with consolidation therapy with durvalumab. NKTR-255 3µg/kg is administered intravenously every 4 weeks in combination with durvalumab (1500mg IV) for up to 1 year (NCT05632809). The primary objectives of the study are safety and ALC normalization at Week 8 after initiation of NKTR-255 and durvalumab post chemoradiation. Secondary endpoints include progression-free survival and overall survival. The trial is currently ongoing at MD Anderson.

Key details and takeaways from the presentation are as follows:

Late-breaking Abstract (LBA) 1489: " REStoring lymphoCytes Using NKTR-255 after chemoradiothErapy in solid tumors (RESCUE): Preplanned Interim Safety and Efficacy Analysis", Lin, S., et al.

The combination of NKTR-255 and durvalumab post chemoradiation was shown to be safe and tolerable with an AE profile consistent with previously reported clinical trials.
Interim pharmacodynamic data demonstrated statistically significant superiority of the eight-week absolute lymphocyte count with NKTR-255 post chemoradiation and in combination with durvalumab versus non-contemporaneous control groups who received either chemoradiation alone or chemoradiation in combination with durvalumab. Additional pharmacodynamic findings following NKTR-255 administration show increased markers of NK cell proliferation and activation.
About NKTR-255

NKTR-255 is a biologic that targets the IL-15 pathway in order to activate the body’s innate and adaptive immunity. Through optimal engagement of the IL-15 receptor complex, NKTR-255 is designed to enhance functional NK cell populations and formation of long-term immunological memory to improve the anti-tumor immune response.

In addition to studies in combination with CAR T cell therapies, NKTR-255 is being studied in a Phase 1 clinical trial sponsored by AbelZeta which is evaluating C-TIL051, a tumor-infiltrating lymphocyte therapy, in anti-PD1 resistant metastatic non-small cell lung cancer (NCT05676749). The JAVELIN Bladder Medley study (NCT05327530), sponsored by Merck KGaA, is also ongoing to evaluate NKTR-255 in combination with avelumab as a maintenance treatment in patients with locally advanced or metastatic urothelial carcinoma (NCT05327530).