Results of a randomized, open-label, multicenter trial to assess the safety, dose, and schedule ofRRx-001(001) in reducing incidence, severity and duration of severe oral mucositis (SOM) inpatients receiving concomitant chemoradiation (CRT) for advanced head and neck cancer (HNC).

Abstract

12081 Background: SOM occurs in 70% of patients receiving CRT for HNC with consequent pain, treatment interruptions and increased costs of care. Supraphysiologic levels of oxidative stress are key SOM initiators. 001 activates nuclear factor erythroid related factor 2 (Nrf2) increasing expression of multiple antioxidant genes including superoxide dismutase glutathione peroxidase and glutathione S-transferase. This trial examined the effect of dose and schedule on safety and efficacy of 001. Primary efficacy endpoint was duration of SOM (WHO criteria assessed); secondary endpoints included time to onset, incidence grade 4 through 60Gy and 70Gy. Methods: Locally advanced HNC treated with definitive or postoperative CRT (cisplatin + RT) received one of 3 001 schedules: (ARM1) 2 doses/wk for 2 weeks (prior to) CRT. ARMS 2, 3: prior to + 2 doses or 6 doses with CRT respectively or standard of care (SOC). Results: 53 patients randomized, 45 evaluable. Benefit trends for endpoints were consistent across all 3 001 arms with greatest effect size in pre-treatment only, ARM1. Compared to SOC, 001 reduced duration of SOM by 45% (40 vs 22 days). Through 60Gy and 70Gy a reduction of 95% and 79% in duration SOM was also observed (17 vs 1 day, and 23 vs 5 days) respectively. No patients in ARM1 developed grade 4, (0% vs SOC 30%). Side effects were comparable to SOC. Conclusions: In this small, open label trial, 001 demonstrated a favorable risk-benefit profile supported by reductions in overall SOM duration including through 60Gy and 70Gy with no grade ARM1 was most effective suggesting short periods of Nrf2 activation before CRT oxidative stress generation may increase the threshold and buffering capacity of upregulated antioxidants. Larger, blinded trials, confirming the observed dose, schedule and treatment effects are warranted. Clinical trial information: NCT03515538 .