J. Mel Sorensen, MD President, and Chief Executive Officer Galera Thereptutics, Inc gives an overview from ASCO 2020 abstract entitled ROMAN: Reduction in oral mucositis with avasopasem manganese (GC4419)"“phase III trial in patients receiving chemoradiotherapy for locally advanced, nonmetastatic head and neck cancer.
Background:
Around 70 % of patients receiving intensity-modulated radiotherapy (IMRT) plus cisplatin for locally advanced head and neck cancer (HNC) develop SOM, identified as WHO Grade 3 or 4, which restricts the ability of patients to absorb solids (Gr 3) or liquids (Gr 4, requiring enteral nutrition). An RT-induced superoxide burst initiates the production of oral mucositis (OM). GC4419, a dismutase mimetic superoxide, interrupts this mechanism by converting superoxide to H2O2. In a published open-label Phase 1b/2a trial (IJROBP 1 Feb 2018), it demonstrated a promising reduction of SOM. In a subsequent randomized, double-blind, placebo-controlled trial in 223 patients receiving IMRT / cisplatin for HNC (ASCO 2018), 90 mg of GC4419 given M-F prior to IMRT showed a statistically significant decrease in SOM duration (p=0.024, median 1.5 days @ 90 mg vs. 19 days placebo) and a significant decrease in SOM incidence (43 percent vs. 65 percent) and severity (incidence (incidence) @ 90 mg vs. 19 days placebo) and a significant decrease in SOM incidence (43 percent vs. 65 percent) The safety outcomes were reasonable and compatible with the IMRT / cisplatin identified toxicities.
Approaches:
335 patients with locally advanced, nonmetastatic head and neck (oral cavity / oropharyngeal) cancer receiving 70 Gy IMRT (> 50 Gy to > 2 oral sites) plus cisplatin (40 mg / m2 qwk x 6-7 or 100 mg / m2 q3wk x 3) at various centers in the United States and Canada are randomized (double-blinded) 3:2 to 90 mg GC4419 or placebo, M-F before each RT fraction. Enrollment is stratified by the timetable for cisplatin and the environment of treatment (definitive versus postop). During RT & weekly for 2 weeks post RT, OM by the WHO scale will be measured twice weekly. The primary endpoint of effectiveness is SOM occurrence via the termination of IMRT. Secondary efficacy endpoints include severity (incidence of Grade 4 OM by the end of IMRT), & SOM days (days from the first to the last SOM for all patients, with patients never developing SOM having by definition 0 days of SOM). SOM dates will be evaluated descriptively for the sub-set evolving SOM. For one year post IMRT, patients will be followed for tumor progression/recurrence and for two years for survival. Data on clinical trials: NCT03689712.