A Phase 1b, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of ST-617 for the Attenuation of Oral Mucositis in Patients Receiving Chemoradiation for Head and Neck Cancer

This Phase 1b part of the study will be an open-label, dose-finding study to: • Test the safety and tolerability of ST-617 (to find out what effects ST-617 has, at different doses) on patients and their oral cavities while they are being treated with chemoradiation for head and neck cancer. • Find the highest dose of ST-617 that can be given without causing bad side-effects (and that will be used in the Phase 2 part of the study). • Find out other things about ST-617 such as: - what the body does to ST-617 after swallowing it - what ST-617 does to certain molecules and genes in the body - how soon severe oral mucositis (OM) starts in patients receiving chemoradiation - how bad OM becomes and how long it lasts, with and without the treatment of ST-617 Participants will receive either best supportive care (BSC) alone, or BSC plus an oral suspension of ST-617 administered daily for 3 days prior to the start of radiation, and then daily during radiation treatment. Radiation treatment duration will last for up to approximately 6 to 8 weeks, however this duration will vary among participants and will depend on clinician's discretion. Initially, a minimum of 3 evaluable patients will receive an oral suspension of ST-617 at the 50 mg dose level plus BSC daily during chemoradiation treatment. After the third patient at the 50 mg dose completes 21 days of oral suspension of ST-617, the Safety Review Committee will review the safety data for the 3 patients and will decide to either expand the number of patients at the dose level or escalate to the next dose (or an intermediary dose level). The 'safe' dose will be determined by medical monitors evaluating a minimum of two dose levels of ST-617 to determine the recommended Phase 2 dose (RP2D) of ST-617 for the attenuation of OM. BSC is defined as a specific oral hygiene regimen based on current guidelines, and practices to minimise the risk of mucosal injury and reduce the risk of secondary oral infection. To assure compliance each patient will be provided with a kit containing supplies necessary for BSC and instructions regarding its use. During the study, patients will be given a kit that has been specifically designed for patients at risk of radiation induced dental disease. This kit contains a toothbrush, toothpaste, dental floss, fluoride gel, oral rinse, and chewing gum. Patients will also receive instructions on how best to use these items to lower the amounts of bacteria on teeth and gums and make teeth more resistant to tooth decay. Radiation treatment duration will last for up to approximately 6 to 8 weeks, however this duration will vary among participants and will depend on clinician's discretion. The dose levels are currently planned to be 50 mg and 100 mg, however, after pharmacokinetic (PK) and safety data are reviewed from each cohort, other doses within the dose range of 50 mg to 150 mg may be evaluated with a minimum of 6 patients enrolled in each dose cohort evaluated. Although patients will be treated with ST-617 for the duration of their chemoradiation therapy, the decision to dose escalate to a new cohort will be based on safety monitoring, occurrence of drug-related toxicities throughout the first 21 days of ST-617 treatment and clinician's discretion. Doses will be provided as one 50 mg dose suspended in one 15 mL bottle. Accountability for the study drug at the study site is the responsibility of the Investigator. The Investigator will ensure that the study drug is used only in accordance with the study protocol. The Investigator may assign the drug accountability responsibilities to a pharmacist or other appropriately trained individual; however, the Investigator remains ultimately responsible for drug accountability. Drug accountability records indicating the drug’s delivery date to the site, inventory at the site and use/dispensing will be maintained. These records will adequately document that study drugs were used and dispensed as specified in the study protocol. Accountability records will include dates, quantities, batch/lot numbers, number of vials, and patient numbers. The Sponsor (or its designee) will review drug accountability records at the site on an ongoing basis during the study. All unused supplies must be inventoried, accounted for, and returned to Sponsor (or its designee), or if authorised, disposed of at the study site. Records of disposal must be maintained with the study records. To ensure compliance each patient will be provided with a kit containing supplies necessary for BSC and instructions regarding their use.