Nektar Therapeutics and collaborators at MD Anderson Cancer Center have presented positive results from a Phase 2 study of NKTR-255 in treating radiation-induced lymphopenia in patients with locally advanced non-small cell lung cancer (NSCLC). The study, presented at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting, showed that NKTR-255, when administered post-chemoradiation and in combination with durvalumab, led to statistically significant lymphocyte recovery compared to historical controls.
NKTR-255 Mechanism and Trial Design
NKTR-255 is a novel polymer-conjugated IL-15 agonist designed to activate and expand natural killer (NK) cells and CD8+ T-cells, while also promoting the survival of memory CD8+ T cells. The Phase 2 single-arm RESCUE trial (NCT05632809) evaluated NKTR-255 (3µg/kg IV) following concurrent chemoradiation and in combination with durvalumab (1500mg IV) every 4 weeks for up to one year. The primary objectives were safety and absolute lymphocyte count (ALC) normalization at Week 8. Secondary endpoints included progression-free survival and overall survival.
Key Findings from the RESCUE Trial
Interim pharmacodynamic data demonstrated a statistically significant improvement in the eight-week absolute lymphocyte count (ALC) with NKTR-255 post-chemoradiation and combined with durvalumab, versus non-contemporaneous control groups that received either chemoradiation alone or chemoradiation plus durvalumab. The study also revealed increased markers of NK cell proliferation and activation following NKTR-255 administration.
According to Steven H. Lin, MD, PhD, Professor of Radiation Oncology at MD Anderson, "Radiation induced lymphopenia is common after chemoradiation therapy and is associated with worse overall survival in multiple solid tumors including lung cancer. 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."
Implications for Cancer Immunotherapy
The findings suggest that NKTR-255 could play a crucial role in enhancing the effectiveness of cancer immunotherapies, particularly in patients undergoing chemoradiation. Mary Tagliaferri, MD, Senior Vice President and Chief Medical Officer at Nektar, noted, "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."
NKTR-255 is also being evaluated in combination with CAR T-cell therapies and in a Phase 1 trial with tumor-infiltrating lymphocyte therapy for anti-PD1 resistant metastatic NSCLC (NCT05676749). Additionally, Merck KGaA is sponsoring a study (JAVELIN Bladder Medley, NCT05327530) to evaluate NKTR-255 with avelumab as maintenance treatment for locally advanced or metastatic urothelial carcinoma.
