FDA Grants Fast Track Designation to RRx-001 for Severe Oral Mucositis in Head and Neck Cancer

The FDA has granted a fast track designation to RRx-001 for the prevention and attenuation of severe oral mucositis associated with chemotherapy and radiation in patients with head and neck cancer, according to a news release from EpicentRx.¹

RRx-001, a direct NLRP3 inhibitor and Nrf2 upregulator with anti-inflammatory and antioxidant properties, is also under investigation for the treatment of small cell lung cancer.

“The fast track designation is great news for EpicentRx, and it puts us one step closer to a potential treatment for this critical unmet need of oral mucositis with RRx-001,” Tony Reid, MD, PhD, chief executive officer of EpicentRx, stated in a news release.

Investigators previously evaluated RRx-001 in the phase 2a PREVLAR trial (NCT03515538). The study evaluated the agent’s efficacy and feasibility in mitigating severe oral mucositis in patients with head and neck cancers who were receiving chemoradiation.² Findings showed that in patients who experienced severe oral mucositis in the 3 RRx-001 treatment arm, the median duration of severe oral mucositis was 8.5 days, 17 days, and 10 days, in arms 1, 2, and 3 respectively, compared with 24 days in the control arm.

When accounting for patients who did not experience severe oral mucositis, the median duration of severe oral mucositis was 5 days for patients in arm 1, 13.5 days for arm 2, 8 days in arm 3, and 18 days in the control arm.

The trial enrolled patients at least 18 years of age with pathologically diagnosed stage III to IVB locally advanced squamous cell carcinoma of the oral cavity or oropharynx who were scheduled to receive definitive or postoperative daily fractionation intensity-modulated radiation therapy at 2.0 Gy to 2.2 Gy for a total dose of 60 Gy to 72 Gy, with concomitant cisplatin given as either weekly at 40 mg/m2 or tri-weekly at 100 mg/m².

Patients were randomly assigned in a 1:1:1:1 fashion to 3 arms receiving RRx-001 or a fourth control arm. Patients in arm 1 received twice weekly infusions of RRx-001 at 4 mg per dose after a premedication dose of dexamethasone at 10 mg for the 2 weeks prior to the start of chemoradiotherapy. Arm 2 consisted of 2 additional doses of RRx-001 at 4 mg after premedication with dexamethasone in weeks 2 and 5 of their chemoradiotherapy regimen. Those in arm 3 received 4 mg of RRx-001 weekly after dexamethasone predosing during the first 6 weeks of chemoradiotherapy. Patients in the control arm were given chemoradiotherapy alone.

Duration of severe oral mucositis served as the trial’s primary end point. Secondary end points included time to onset and incidence of severe oral mucositis, duration and incidence of ulcerative oral mucositis, and patient-reported pain.³

Regarding safety, the incidence of severe adverse effects (AEs) was comparable across RRx-001 arms and consistent with the known toxicities of chemoradiotherapy.² Twenty-two severe AEs were reported in 21 patients, and none were attributed to RRx-001.

Additionally, the regulatory agency has accepted an investigational new drug application from EpicentRx to initiate the follow-on phase 2b KEVLARx trial in the same head and neck cancer population.

References

1. EpicentRx receives fast track designation from the U.S. FDA for lead asset, RRx-001, to prevent/attenuate chemotherapy and radiation treatment induced severe oral mucositis. News release. EpicentRx. March 29, 2023. Accessed March 30, 2023. https://www.epicentrx.com/2023/
2. Bonomi M, Blakaj DM, Kabarriti R, et al. PREVLAR: phase 2a randomized trial to assess the safety and efficacy of RRx-001 in the attenuation of oral mucositis in patients receiving head and neck chemoradiotherapy. Int J Radiat Oncol Biol Phys. Published online January 14, 2023. doi:10.1016/j.ijrobp.2022.12.031
3. Safety and efficacy of RRx-001 in the attenuation of oral mucositis in patients receiving chemoradiation for the treatment of oral cancers (PREVLAR). ClinicalTrials.gov. Updated January 11, 2021. Accessed March 30, 2023. https://clinicaltrials.gov/ct2/show/NCT03515538