EUSOM: Phase 2 Trial of Avasopasem Manganese (GC4419) for Oral Mucositis in Patients Receiving Chemoradiotherapy for Locally Advanced, Nonmetastatic Head and Neck Cancer

Abstract

<h3>Purpose/Objective(s)</h3> Severe oral mucositis (SOM; gr 3–4 on the WHO scale) occurs in about 70% of patients receiving chemoradiotherapy (CRT) for head and neck cancer (HNC). Current treatment approaches focus primarily on symptoms. (Elad 2020) Avasopasem (AVA; GC4419) is an investigational selective dismutase mimetic that rapidly converts superoxide to hydrogen peroxide, potentially interrupting SOM development. (Riley 2007, Sonis 2001) In a phase 2 study, AVA vs placebo reduced SOM duration, incidence, and severity (gr 4 incidence) in patients with locally advanced HNC undergoing CRT (Anderson 2019), prompting initiation of the phase 3 ROMAN study (NCT03689712). The objective of the phase 2 EUSOM open-label trial was to assess the feasibility (safety and efficacy) of a vasospasm in European patients receiving CRT for locally advanced squamous cell carcinoma of the head and neck. <h3>Materials/Methods</h3> In EUSOM (NCT04529850), patients with locally advanced, nonmetastatic HNC in Belgium, Czech Republic, Germany, Poland, Spain and Switzerland received AVA 90 mg IV before each daily fraction (2.0–2.2 Gy, M–F) of intensity-modulated radiation therapy (IMRT; 60–72 Gy over appx. 7 weeks), with investigator's choice of cisplatin 100 mg/m² q3wks x 3 or 40 mg/m² weekly x 6–7. WHO grade of OM was assessed twice weekly through IMRT then weekly for 4 weeks. The primary endpoint was safety. SOM incidence, severity (gr 4), and duration were secondary endpoints. <h3>Results</h3> N=38 enrolled, 37 (median age 61 [range 45–79]; 81% male) received ≥1 dose of AVA, 33 received ≥ 60 Gy IMRT and ≥ 5 wks AVA (per protocol). Primary tumor: oral (n=15), oropharyngeal (n=20), or other (n=2). AVA median duration of exposure was 6.7 weeks. Median cumulative IMRT dose was 69.3 Gy (range 14–74). Mean cumulative cisplatin dose was 245.5 mg/m² and 212.3 mg/m², respectively, for patients receiving q3w (11/37) and weekly (26/37) schedules; 91% and 58%, respectively, received ≥200 mg/m². The most frequent adverse events (AEs) were lymphopenia, nausea, leukopenia, and anemia. Hypotension occurred in 19% (n=7, 3 gr 3) and was the most frequent AVA-related AE (n=5). Serious AEs (N=18; 49%) included pneumonia (n=3), COVID-19 (n=2), and hypotension (n=2, 1 AVA-related leading to AVA discontinuation). SOM efficacy for the full and per protocol population (≥60 Gy RT and ≥25 infusion of AVA; n=33) are shown in the table. <h3>Conclusion</h3> The AE profile observed in EUSOM was comparable to published data and suggested that vasospasm was well tolerated in these patients. SOM incidence appeared lower than historic expectations. Funder Galera Therapeutics, Inc.