Abstract 1846P
Background
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.
Methods
A dose escalation study, designed to evaluate the safety, tolerability, PK, PD and efficacy of ST-617 administered as an oral suspension, 1-2 hours before CRT for H&N cancers. 18 pts maximum will be enrolled, up to 6 pts per dose. 3 days prior to CRT, pts will begin with daily ST-617 administration, until end of treatment. Safety outcomes, using standard CTCAE criteria will be used. If no toxicity, the next dose level will be evaluated. OM occurrence and severity will be assessed using a template developed by Primary Endpoint Solutions and OM scores will be centrally assigned to the WHO, NCI-CTC and RTOG scales. The primary efficacy endpoint will be based on observed severity and (WHO grades 3 or 4) duration of OM incidence vs historical controls. PD tracking will measure total ROS/RNS, GSH/GSSG, regulation in plasma and buccal epithelial cells.
Results
10 pts completed the 50 & 100mg/day with no safety issues. Dose 150 mg/day is ongoing with 3 pts. No early dose limiting toxicity (DLT) or serious Adverse Event linked to ST-617 were observed. 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.
Conclusions
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, controlled, double blind trial is planned with the recommended dose.
Clinical trial identification
ST617-101 trial is registered in South Africa. The SAHPRA number is 20180138 ST617-101 trial is registered in Europe EUDRACT number: 2020-000774-19.
Editorial acknowledgement
Legal entity responsible for the study
Supportive Therapeutics, LLC.
Funding
Supportive Therapeutics.
Disclosure
D. Osei-Fofie: Honoraria (institution), Advisory/Consultancy: Bayer. J.A. Wetter: Travel/Accommodation/Expenses: Genentech; Honoraria (institution), Travel/Accommodation/Expenses: Roche. B. Framroze: Advisory/Consultancy, Travel/Accommodation/Expenses: Supportive Therapeutics; Leadership role, Travel/Accommodation/Expenses: Hofest Biocare. J. Gelfand: Advisory/Consultancy, Travel/Accommodation/Expenses: Supportive Therapeutics; Research grant/Funding (self): Henry Shine; Advisory/Consultancy: Aperysis. A. Lategan: Advisory/Consultancy, Travel/Accommodation/Expenses: Supportive Therapeutics. P. Song: Leadership role, Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options: NKMax. M. Dimitriu: Advisory/Consultancy, Travel/Accommodation/Expenses: Supportive Therapeutics. S. Sonis: Licensing/Royalties: Predictive Genomics; Leadership role, Research grant/Funding (institution), Travel/Accommodation/Expenses, Officer/Board of Directors: Bio Models. All other authors have declared no conflicts of interest.