Avasopasem manganese provided a clinically meaningful benefit to patients with locally advanced, nonmetastatic head and neck cancer (HNC) who developed treatment-related severe oral mucositis (OM), according to results of a phase 3 trial presented at the 2022 ASCO Annual Meeting.

Intensity-modulated radiotherapy (IMRT) plus cisplatin is the standard of care for locally advanced HNC. But a high percentage of patients develop severe OM (WHO grade 3 or 4), limiting their ability to eat solids (grade 3) or liquids, often requiring intravenous or tube feeding (grade 4). There are no drugs approved in the United States for the treatment of severe OM in patients with HNC.

Avasopasem converts radiotherapy-induced superoxide to hydrogen peroxide. Superoxide initiates tissue damage and an inflammatory cascade that leads to OM. Avasopasem protects normal cells from, and potentially sensitizes cancer cells to, radiotherapy, Carryn M. Anderson, MD, of the University of Iowa Hospitals and Clinics in Iowa City, explained when presenting this research at ASCO 2022.

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Data from a phase 2b trial were promising, suggesting that avasopasem at 90 mg could reduce the duration of severe OM (P =.024), the incidence of severe OM through IMRT (P =.009), and the incidence of grade 4 OM (P =.045). Compared with placebo, avasopasem had a comparable adverse event profile, and tumor outcomes were maintained at 1 and 2 years.

In the phase 3 ROMAN trial (ClinicalTrials.gov Identifier: NCT03689712), the safety and efficacy of avasopasem was assessed in patients with locally advanced, squamous cell carcinoma of the oral cavity or oropharynx who were eligible for standard care: 7 weeks of IMRT plus cisplatin.

Patients received avasopasem at 90 mg or placebo, administered as a 60-minute IV infusion, Monday to Friday, ending no more than 60 minutes prior to radiotherapy, and were stratified by surgery status (postop or definitive) and cisplatin schedule (every 3 weeks or weekly). Trained evaluators examined the patients for oral mucositis biweekly during radiotherapy and weekly for 2 weeks thereafter.

The primary endpoint was the incidence of severe OM through IMRT. Secondary endpoints were the duration of severe OM through 2 weeks post-IMRT, and the incidence and duration of grade 4 OM through IMRT.

A total of 455 patients at 69 sites in the United States and Canada were enrolled. Of 407 patients who were randomly assigned and treated, 241 received avasopasem and 166 received placebo. The median age was 61 years, 86% were men, and 80% had oropharyngeal cancer.

Avasopasem was associated with a significant 16% relative reduction in the incidence of severe OM through IMRT. The incidence was 54% with avasopasem and 64% with placebo (P =.045).

Avasopasem was also associated with a 56% relative reduction in the duration of severe OM through follow-up. The median duration was 8 days with avasopasem and 18 days with placebo (P =.002).

The incidence and duration (mean number of days) of grade 4 OM was reduced by 27% (P =.052) and 24% (P =.143), respectively, with avasopasem.

Avasopasem is the first drug to show statistically significant and clinically meaningful reductions in both incidence and duration of severe OM, Dr Anderson reported. Nominal, meaningful improvements in the severity or incidence of grade 4 OM and onset of severe OM were also reported. These findings are consistent with results of the phase 2b study.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Anderson CM, Lee CM, Kelley JR, et al. ROMAN: Phase 3 trial of avasopasem manganese (GC4419) for severe oral mucositis (SOM) in patients receiving chemoradiotherapy (CRT) for locally advanced, nonmetastatic head and neck cancer (LAHNC). Presented at ASCO 2022; June 3-7, 2022. Abstract 6005.