1489 REStoring lymphoCytes using NKTR-255 after chemoradiothErapy in solid tumors (RESCUE): preplanned interim safety and efficacy analysis
Year: 2024
Type: conference-abstract
Abstract: Background Radiation induced lymphopenia (RIL) is common after chemoradiation therapy (CRT) and can reduce efficacy of immunotherapies. IL-15 is a pleiotropic cytokine with roles in innate and adaptive immunity and is essential for lymphocyte formation, immunological memory and cell survival. NKTR-255 is an investigational polymer-conjugated rhIL-15 receptor agonist with extended exposure and sustained activation of the IL-15 pathway. Here, we present a prespecified interim analysis of a Phase II study evaluating safety and PK of NKTR-255 for restoring absolute lymphocyte count (ALC) after CRT in locally advanced non-small cell lung cancer (LA-NSCLC). Methods NKTR-255 (3µg/kg) is given after CRT (day 0), with repeat doses given every 4 weeks concurrently with durvalumab up to 1 year. This trial is designed to enroll up to 30 patients with ongoing safety and futility analysis after the first 10 evaluable patients. The primary objectives are safety of NKTR-255 after CRT, incidence of treatment-related adverse events (TRAE) of Grade 3+ (G3) radiation pneumonitis, and ALC normalization after administration of NKTR-255 and durvalumab at Day 60 after CRT (figure 1). Early stopping rules are in place to control incidence of grade 3+ radiation pneumonitis, and futility monitoring for efficacy, defined as ALC recovery >1000 cells/µL. Results As of September 5th, 2024, 15 enrolled patients received at least one dose of NKTR-255. Preliminary PK analyses showed a mean half-life of 32 hours with no accumulation after repeat dosing, consistent with prior studies. One patient developed G3 pneumonitis. Two patients had transient G3 liver enzyme elevation and 1 patient had transient G3 sinus tachycardia. The most common TRAEs were fever, chills, sinus tachycardia, ALT elevation and dyspnea. Among the enrolled 15 patients, 10 patients, who completed at least 2 doses of the study treatment and reached week 8 evaluation, are evaluable for ALC assessment. At week 8, ALC recovery was met for 9 evaluable patients and 1 patient had increased ALC from G2 to G1. This finding greatly exceeds the minimal success rate futility cutoff. At Cycle 1 day 8 (C1D8), the median increase in ALC was 2.35-fold (range 1.46–4.33) and at C2D8, it was 3.57-fold (range 1.84–8.09). Conclusions NKTR-255 after CRT was safe and biologically active in reverting RIL. These preliminary findings support the MOA of reversal of lymphopenia with NKTR-255. After meeting the initial safety and efficacy threshold, the trial continues accrual at MDACC (NCT05632809). Trial Registration NCT05632809. Ethics Approval All patients are consented to an institutional review board approved clinical trial protocol.
Authors: Steven H Lin, Ying-Shiuan Chen, Priti Gupta, Madison Kahanek, Rebecca S Tidwell, Hyunsoo Hwang, Peter F Thall, Stephen G Chun, Joe Y Chang, Zhongxing Liao, Zachary Lee, Mario A Marcondes, Mary Tagliaferri, George R Blumenschein, Janet Tu, John V Heymach, Mehmet Altan
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4404067345