GC4419, also known as avasopasem manganese, has successfully completed two clinical trials in which it was evaluated for reduction of severe oral mucositis in patients with head and neck cancer undergoing radiation therapy and also receiving cisplatin, a chemotherapy drug.1, 2 We demonstrated proof-of-concept with GC4419 for this use in a randomized, double-blinded, placebo-controlled 223-patient Phase 2b trial. In the trial, GC4419 met the primary endpoint by demonstrating a 92% reduction in median duration of SOM in the 90 mg treatment arm as compared to placebo, which was statistically significant and consistent with the results of our Phase 1b/2a SOM trial.2 Key secondary endpoints evaluating the incidence and severity of SOM also demonstrated substantial dose-dependent reductions of 34% and 47%, respectively, in the 90 mg treatment arm, and GC4419 was well tolerated in this trial.2
This chart demonstrates that (1) fewer patients in the 90 mg treatment arm developed SOM than in the placebo arm, (2) fewer patients in the 90 mg treatment arm developed Grade 4 OM than in the placebo arm, and (3) on average, SOM did not last as long for patients in the 90 mg treatment arm. This is consistent with the observed reductions in the individual numerical endpoints of median duration, incidence and severity.
In addition, consistent with the findings in our other clinical trials and pre-clinical studies to date, in this trial, the anti-cancer efficacy of radiotherapy was maintained through one year when combined with GC4419. Following consultation with the FDA, we initiated a single confirmatory, randomized, placebo-controlled Phase 3 registrational trial of a 90 mg dose of GC4419 in patients with locally advanced head and neck cancer receiving radiotherapy, which we refer to as the ROMAN Trial.
GC4419 has received Breakthrough Therapy and Fast Track designations from the U.S. Food and Drug Administration for the reduction of the incidence and severity of radiation and chemotherapy-induced OM. For additional details on ongoing clinical trials with GC4419, please visit www.clinicaltrials.gov.
- Anderson CM, Sonis ST, Lee CM, et al. Phase 1b/2a Trial of the Superoxide Dismutase Mimetic GC4419 to Reduce Chemoradiotherapy-Induced Oral Mucositis in Patients With Oral Cavity or Oropharyngeal Carcinoma. Int J Radiat Oncol. Published Online October 16, 2017.
- Anderson CM, Lee CM, Saunders D, et al. A Randomized, Placebo (PBO) Controlled, Double-Blind P2b Trial of GC4419 (Avisopasem Manganese) to Reduce Severe
Radiation-Related Oral Mucositis (SOM) in Patients (pts) with Locally Advanced Squamous Cell Cancer of the Oral Cavity (OC) or Oropharynx (OP). Int J Radiat Oncol. Volume 102, Issue 3, Supplement, Page S109