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

Abstract

<h3>Purpose/Objective(s)</h3> The number of patients diagnosed with early-stage NSCLC has been increasing with screening programs and more frequent thoracic imaging. Many patients are not ideal surgical candidates and SBRT offers an effective alternative. SBRT for larger and/or centrally located tumors is described with higher risk of toxicity and poorer local control (Timmerman 2006). Improving the safety and efficacy of SBRT with GC4711 may be of significant value in today's NSCLC management for all patients. GC4711 converts superoxide to hydrogen peroxide and has the potential to act as a radiation response modifier, increasing both tumor control and safety of SBRT. In preclinical models, the addition of selective dismutase mimetics to SBRT regimens enhanced tumor control while also protecting normal tissues from radiation damage (Sishc, AACR 2018). Consistent with this, GC4711 augmented the anti-tumor activity of SBRT in NSCLC xenograft mouse models. <h3>Materials/Methods</h3> This Phase 1/2 trial is designed to test the safety of GC4711 and its potential to reduce lung injury due to SBRT and improve tumor control for early stage cT1c-3N0M0 peripheral or centrally located (within 2cm of the proximal bronchial tree) NSCLC. An open-label, Phase 1 cohort of 5 subjects receiving GC4711, 100 mg IV (15 min), prior to each of 5 consecutive daily (M-F) SBRT fractions of 10-12Gy (Bezjak 2019) will be followed by a placebo-controlled, double-blind Phase 2 cohort of approximately 66 subjects randomized to either GC4711 or placebo concurrent with SBRT. For the primary endpoint, decline in diffusion capacity of carbon monoxide at 6 months will be compared to baseline (Stone 2015). All subjects will be followed for 12 months to report clinical (CTCAE 5.0) and radiographic pneumonitis, measured at the same time-points as quarterly lung function tests, other adverse effects, tumor control (RECIST 1.1), survival and quality of life (FACT-L). Exploratory correlative studies include ctDNA and immune profiling. <h3>Results</h3> Trial-in-progress NCT04476797 <h3>Conclusion</h3> GC4711 may improve the benefit-risk ratio of 5-fraction SBRT in early-stage NSCLC; improving tumor control while reducing the risk of lung injury.