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ROMAN showed that an infusion of avasopasem before each dose of radiotherapy cut severe mouth ulcers during head and neck chemoradiation from about two thirds of patients to about half and shortened them from 18 days to 8, but the effect was smaller than an earlier trial had promised and the FDA asked for another study before approval.
ROMAN (NCT03689712; organisation id GTI-4419-301) was a double-blind, placebo-controlled phase 3 trial of avasopasem manganese (GC4419), a superoxide dismutase mimetic, in patients with locally advanced head and neck cancer receiving 60 to 72 Gy of intensity-modulated radiotherapy (more than 50 Gy to at least two oral mucosal sites) with cisplatin every three weeks or weekly. Patients were randomised 3:2 to avasopasem 90 mg or placebo before each radiotherapy fraction. Severe oral mucositis (WHO grade 3 or 4) was assessed twice weekly during radiotherapy and weekly for two weeks after; the primary endpoint was its cumulative incidence through the end of radiotherapy.
Of 455 patients randomised, 407 (241 avasopasem, 166 placebo) formed the primary analysis population. Severe oral mucositis occurred in 54 percent on avasopasem versus 64 percent on placebo (relative risk 0.84; 95 percent CI 0.71 to 1.00; p = 0.045), and its median duration was 8 versus 18 days (p = 0.002); onset was nominally delayed (median 49 versus 38 days). Grade 4 mucositis incidence and duration were not significantly reduced (27 percent, p = 0.052; 24 percent, p = 0.143). Adverse-event frequencies were comparable, tumour outcomes were maintained at one year, and two-year overall survival was 89 percent (95 percent CI 84 to 93) with avasopasem versus 93 percent (88 to 96) with placebo.
The eClinicalMedicine 2025 report states that the incidence benefit was smaller than the phase 2b trial had predicted, that a contribution of avasopasem to adverse events could not be excluded, and that ROMAN did not give a sufficiently favourable benefit-risk determination for FDA approval; a confirmatory phase 3 was requested. The FDA issued a complete response letter in August 2023, and the drug remains investigational. The registry condition is oral mucositis rather than a cancer, which is why the automated pass never attached the trial to the drug.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
455 enrolled.
Relative risk 0.84 vs placebo; 95% CI 0.71 to 1.00
Source95% CI 84 to 93; tumour outcomes were maintained at one year · 95% CI 88 to 96
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Severe oral mucositis (WHO grade 3 or 4) incidence through the end of radiotherapyprimary | Avasopasem manganese 90 mg | 241 | 54% | - | 0.045 | link |
| Placebo | 166 | 64% | ||||
| Median duration of severe oral mucositis | Avasopasem manganese 90 mg | 241 | 8 days | - | 0.002 | link |
| Placebo | 166 | 18 days | ||||
| Median time to onset of severe oral mucositis | Avasopasem manganese 90 mg | 241 | 49 days | - | - | link |
| Placebo | 166 | 38 days | ||||
| Overall survival at 2 years | Avasopasem manganese 90 mg | - | 89% | - | - | link |
| Placebo | - | 93% |
Shares Radioprotectors and normal-tissue sparing drugs, Head and neck squamous cell carcinoma.
Shares Radioprotectors and normal-tissue sparing drugs, Head and neck squamous cell carcinoma.
Shares Radioprotectors and normal-tissue sparing drugs, Head and neck squamous cell carcinoma.