GRECO-1: Phase 1/2 Study of Stereotactic Body Radiation Therapy (SBRT) with or without Rucosopasem (GC4711) for Early Stage, Peripheral or Centrally Located Non-Small Cell Lung Cancer (NSCLC)

Abstract

<h3>Purpose/Objective(s)</h3> The number of patients diagnosed with early-stage non-small cell lung cancer (NSCLC) has been increasing with screening programs and more frequent thoracic imaging. SBRT is an alternative for patients who are not candidates for surgery. SBRT for larger and/or centrally located tumors may have reduced efficacy and lead to higher-grade toxicity (Timmerman 2006; Dunlap 2010). Rucosopasem (GC4711) is one of a class of investigational selective dismutase mimetics that rapidly and specifically produces hydrogen peroxide from superoxide (Riley 2006). In preclinical models including NSCLC, the addition of a dismutase mimetic to SBRT regimens demonstrated mechanism-related anticancer synergy with SBRT while protecting normal tissues from radiation damage (Sishc 2021). The purpose of this trial is to test the hypothesis that rucosopasem may improve tumor control without increasing pulmonary toxicity after SBRT. <h3>Materials/Methods</h3> This phase 1/2 trial is designed to test the safety of rucosopasem and its potential to improve tumor control and reduce lung injury due to SBRT for cT1c-3N0M0 peripheral or centrally located (within 2 cm of the proximal bronchial tree) NSCLC. An open-label, phase 1 run-in cohort of 5 patients received rucosopasem 100 mg as a 15-minute IV infusion within a 180-minute window prior to each of 5 SBRT fractions of 10–12 Gy delivered on sequential weekdays. A placebo-controlled phase 2 cohort of approximately 66 patients randomized to either rucosopasem or placebo concurrent with SBRT follows and is ongoing. The primary endpoint for phase 1 is dose-limiting toxicities during treatment or within 30 days post-SBRT, and for phase 2, in-field tumor response. Reduction from baseline in diffusion capacity of lung for carbon monoxide (DLCO) at 6 months (Stone 2015) is a secondary endpoint for phase 2. Progression-free and overall survival, locoregional control, and distant metastasis rate will be followed over 24 months. Additional secondary endpoints include clinical (CTCAE 5.0) and radiological pneumonitis, measured at the same timepoints as quarterly lung function tests, and other adverse events. Trial-in-progress NCT04476797 is currently enrolling. This study is funded by Galera Therapeutics, Inc. <h3>Results</h3> TBD <h3>Conclusion</h3> TBD