Phase Ib, international, dose-escalation study to evaluate the safety, pharmacokinetics (PK) and efficacy of ST-617 for the attenuation of oral mucositis (OM) in patients receiving chemoradiation (CRT) for head and neck (H&N) cancer.

OM is a common, painful, and costly toxicity associated with cytotoxic regimens used to treat H&N cancers. There is currently no approved intervention to successfully prevent or delay OM onset among patients being treated with CRT. Oxidative stress is a critical event in the pathogenesis of CRT associated OM. ST-617 has marked anti-oxidative activity/properties and has previously been studied in multiple human clinical trials. Supportive Therapeutics is developing ST-617 for the attenuation of OM onset, duration and severity. A dose escalation trial in which ST-617 administered as an oral suspension, 1-2 hours before the administration of daily RT fractions. 18 patients with diagnoses of oral or oropharyngeal CA were enrolled (up to 6 pts/dose). Patients received concomitant cisplatin either weekly or tri-weekly. ST-617 was administered 3 days prior to CRT, and then continuing daily until the end of treatment. Safety outcomes, using CTCAE criteria (v 4.03) were used. OM occurrence and severity were assessed by trained and validated evaluators using WHO, NCI-CTC and RTOG criteria; scores were centrally assigned. The primary efficacy endpoints included the incidence and duration of SOM (WHO grades 3 or 4) vs historical controls. PD tracking measured total ROS/RNS, GSH/GSSG, regulation in plasma and buccal epithelial cells. 17 pts completed the 50, 100 and 150mg/day with no safety issues. No early dose limiting toxicity (DLT) or serious Adverse Event linked to ST-617 were observed. AEs observed were mainly nausea which is usually associated with CRT as expected. The 100 mg/day dose has been well tolerated with no grade 4 OM. No CRT dose interruptions or delays due to OM has been observed. Total ROS/RNS levels in plasma and buccal samples shows significant decrease with increased ST-617 dosing from 50 to 100 mg/day. ST-617 administration shows a very good safety profile. Favorable signs of efficacy in preventing the duration and severity of OM with a physiologically relevant mode of action response have been noted. A randomized, double blind trial is planned with the recommended dose.