NKTR-255 Shows Promise in Reversing Radiation-Induced Lymphopenia in NSCLC
Key Insights
NKTR-255, combined with durvalumab, demonstrates potential in treating radiation-induced lymphopenia in locally advanced NSCLC (search) patients undergoing chemoradiation.
Interim phase 2 trial results indicate NKTR-255 significantly improved absolute lymphocyte count (ALC) compared to control groups post-chemoradiation.
Pharmacodynamic data showed increased NK cell proliferation and activation, supporting NKTR-255's ability to enhance immune responses.
Treatment with NKTR-255 combined with durvalumab (Imfinzi) may offer an effective approach for radiation-induced lymphopenia in patients with locally advanced non-small cell lung cancer (NSCLC (search)) undergoing chemoradiation, according to phase 2 trial results presented at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting.
NKTR-255 is a novel polymer-conjugated IL-15 (search) agonist designed to activate and expand natural killer (NK) cells and CD8-positive T-cells while promoting the survival of memory T-cells. Preclinical and clinical studies have demonstrated its ability to stimulate a broad range of immune cells and enhance lymphocyte trafficking. It is currently being investigated in combination with cellular therapies and immune checkpoint inhibitors.
Impact on Lymphocyte Counts
"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 Cancer Center. "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 (search)."
The phase 2 study is part of the ongoing REStoring lymphoCytes Using NKTR-255 after chemoradiothErapy in solid tumors (RESCUE) trial. NKTR-255 3µg/kg is administered intravenously every 4 weeks in combination with durvalumab (1500 mg intravenously) for up to 1 year.
The primary end points of the trial are to estimate the level of lymphocyte restoration after administration of NKTR-255 concurrently with durvalumab after chemoradiation and to monitor the safety of NKTR-255. Secondary end points of the study include estimating progression-free survival (PFS) and overall survival (OS) time distribution. Additional exploratory end points include pharmacokinetics, pharmacodynamics, and assessing the correlation between circulating tumor DNA and efficacy measurements.
Interim Efficacy and Safety
Interim results suggest that NKTR-255, in combination with the anti–PD-L1 therapy durvalumab, significantly improved absolute lymphocyte count (ALC) in patients with NSCLC (search) following chemoradiation therapy. Findings showed that NKTR-255 outperformed control groups among patients receiving either chemoradiation alone or chemoradiation plus durvalumab, regarding ALC recovery at the 8-week mark.
In addition to ALC improvements, interim pharmacodynamic data revealed increased NK cell proliferation and activation, further supporting NKTR-255’s ability to enhance immune responses post-chemoradiation.
The safety profile of NKTR-255 in this setting was consistent with prior studies, with no unexpected adverse effects reported.
Future Directions
“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 Therapeutics.
The study is continuing to evaluate NKTR-255’s effects on PFS and OS, with ongoing enrollment at MD Anderson.