AESOP: Phase 2 Open-Label Trial of Avasopasem Manganese (GC4419) for Reduction of Esophagitis in Patients Receiving Chemoradiotherapy for Nonmetastatic Lung Cancer

Abstract

<h3>Purpose/Objective(s)</h3> National Cancer Institute (NCI) grade 3+ esophagitis has been reported in up to 20% of advanced lung cancer patients receiving standard fractionation radiotherapy with concurrent chemotherapy (Provencio 2011, Curran 2011). Avasopasem (GC4419) is an investigational selective dismutase mimetic that rapidly and selectively converts superoxide to hydrogen peroxide, interrupting the initiation of radiation-induced mucosal injury (Thompson 2010, Sonis 2021). Avasopasem demonstrated the potential to reduce severe oral mucositis due to chemoradiotherapy for head and neck cancer in a randomized phase 2 clinical trial (Anderson 2019), supporting the hypothesis that avasopasem might reduce severe radiation-induced esophagitis in patients with lung cancer. <h3>Materials/Methods</h3> In a single-arm open-label trial, patients with stage 3 or post-operative stage 2B non-small cell lung cancer (NSCLC) or limited stage small-cell lung cancer (LS-SCLC) received 90 mg avasopasem by 60-minute infusion prior to radiation therapy (1.8–2.0 Gy 5 days/week up to 60 Gy total), in combination with investigator's choice of chemotherapy other than gemcitabine. Primary objective to assess the incidence of acute (NCI ≥gr 2) radiation esophagitis, with observed incidence of grade 3–4 radiation esophagitis as a secondary endpoint. <h3>Results</h3> A total of 39 patients were enrolled and received at least 1 dose of avasopasem: median age 64 (range 38–85); 22 (56.4%) were male; 95% performance status (PS) 0 or 1. Thirty-two (82.1%) had NSCLC and 7 (17.9%) had LS-SCLC. Median duration of exposure to avasopasem was 43.0 days (range 2–54). Preliminary results with data analysis ongoing showed 14 of 29 evaluable patients (48.3%) experienced acute esophagitis at week 6 (95% confidence interval [CI], 29.5–67.5). Of these, 13 (44.8%) were grade 2 and 1 (3.4%) was grade 3; there were no grade 4 events. Adverse events (AEs, all grades) considered possibly related to avasopasem occurring in at least 15% of patients were nausea (36%), paresthesia (26%), dizziness, fatigue (21% each), and hypotension (15%). Three patients had grade 3 AEs (7 events) possible related to avasopasem (nausea, vomiting, dehydration, hypokalemia, dysphagia, muscular weakness, hypoxia). <h3>Conclusion</h3> In this phase 2 open-label study, grade 3 esophagitis was infrequent with avasopasem at an unscheduled interim analysis. The AE profile appeared consistent with expectations for standard therapy and avasopasem appeared well tolerated. Final data will be presented at the conference. This study (NCT04529850) is funded by Galera Therapeutics, Inc.