NG11-2 phase-Ib trial to prevent/reduce severe oral mucositis induced by radiotherapy.

12121 Background: Radiation-induced oral mucositis (RIOM) affects up to 80% of people undergoing treatment for head and neck cancer (HNC), reaching nearly 100% in altered or accelerated fractional radiation. Current approaches necessitate multiple supportive care pharmacotherapies with no approved preventative pharmaceutical products available for the reduction of RIOM in patients with HNC. To address this unmet medical need an innovative oral topical vasoconstrictor solution (NG11-2) has been developed and a phase-Ib dose escalation study carried out to assess the safety and preliminary efficacy of NG11-2 in preventing/reducing RIOM in patients undergoing treatment for HNC. Methods: In this single arm, multi-centre, phase-1b “2+4” dose escalation study (NCT06669390) using NG11-2, 15 participants, with a diagnosis of HNC and scheduled to receive radiotherapy with at least 30Gy exposure to the oral cavity and/or buccal mucosa (with or without chemotherapy) were enrolled, with 2 each into the 0.92mg/mL, 1.83mg/mL, 3.66mg/mL and 5.5mg/mL dose cohorts. An additional 7 patients were enrolled in the 5.5mg/mL cohort as an expansion phase. Safety was the primary endpoint, with secondary endpoints including duration, incidence and time to onset of severe RIOM using World Health Organization [WHO], Radiation Therapy Oncology Group [RTOG], and National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] V5 grading criteria, with severe levels being Grade 3 or above. Patient Reported Outcome Measurements were also performed. The Kaplan-Meier method was applied to the expanded dose cohort to estimate the median duration, incidence and time to onset of severe RIOM. Results: No Dose Limiting Toxicities or Serious Adverse Reactions were observed during the study. The duration and incidence of severe RIOM were reduced in the 5.5mg/mL cohort (15.5 days and 44.4% using WHO criteria respectively, 14 days and 33.3% using RTOG respectively, 17days and 33.3% using NCI-CTCAE respectively), relative to the 0.92mg/mL cohort (18-46 days and 100% respectively using the WHO, RTOG and NCI-CTCAE criteria). Conclusions: NG11-2 is well tolerated in the patient population included in this study. NG11-2 shows encouraging preliminary efficacy results which support proceeding to larger scale confirmation studies. Clinical trial information: NCT06669390 .