ESTRO 2024 - Abstract Book

S1298

Clinical - Head & neck

ESTRO 2024

Severe oral mucositis (OM) is a debilitating side effect observed in patients with head and neck cancer (HNC) undergoing radiotherapy (RT), with or without chemotherapy (CT). To date, there are no approved pharmaceutical products with clinically meaningful efficacy to prevent severe OM in patients undergoing chemoradiotherapy or RT for their HNC treatment. Topical application of vasoconstrictors has been explored as a preventive therapeutic for severe OM in the past years, with preliminary safety and efficacy observed in animal models and bone marrow transplant patients (Li NF, 2022). NG11-2, an investigational pharmaceutical product utilising a well-known vasoconstrictor drug substance, is being developed as a mouthwash solution administered to patients with HNC in RT clinics prior to each fraction of RT. Currently, five cancer centres within the National Health Service system are involved in this Phase-Ib study across the United Kingdom. (EudraCT Number: 2022-002409-99; IRAS Number 1004528).

Objectives:

1. To evaluate the safety profile of NG11-2 investigational mouthwash pharmaceutical product with a range of doses; 2. To observe the preliminary efficacy of NG11-2 on preventing/delaying the onset of severe OM during

radiotherapy (RT) with/without concurrent chemotherapy (CT); 3. To identify the Recommended Phase 2 Dose (RP2D) of NG11-2.

Material/Methods:

Materials : NG11-2 Investigational medical products are supplied by the Sponsor (VasoDynamics Ltd) at a range of doses including 0.92mg/ml, 1.83mg/ml, 3.66mg/ml and 5.5mg/ml.

Patients : Patients with HNC undergoing RT, with or without concomitant CT. Concomitant CT consists of either Cisplatin weekly 40mg/m2 or Cetuximab at standard doses.

Methods :

1. Dose Escalation: The dose escalation scheme follows a “2+4” Dose Escalation design (Revathi 2017) starting at 0.92mg/mL on 2 patients and escalating to the next dose level if no Dose Limiting Toxicity (DLT) is seen on these two patients in each cohort. Additional 4 patients will be added into the dose cohort when one of the 2 patients experiences DLT at the dose level. The definition of DLT includes the parameters to assess the oral local toxicity and systemic safety. 2. Endpoints parameters: The primary endpoint of the study is the occurrence of DLTs and serious adverse events (SAE). The secondary endpoints include the incidence, duration and the time to onset of severe OM defined as Grade 3 and above OM in WHO/RTOG/CTCAEv5.0 scales. OM is assessed by using a tailor-made OM assessment worksheet and a Patient Reported Outcome Measure (PROM) questionnaire. 3. The following inclusion criterion was applied to select the patients with high likelihood to develop severe OM: scheduled to receive a mean radiation dose of no less than 30Gy on either (a) Extended Oral Cavity, or (b) Buccal Mucosa, or (c) Lips, according to CT based delineation of Organ-At-Risk (OAR) Guideline (Brouwer et al 2015). 4. RP2D will be defined after completion of the dose escalation part of the study, by assessing the safety profiles and the patterns of severe OM among enrolled patients. 5. A colour-heatmap of OM scores of each patient week-by-week throughout the treatment period will be used to display the preliminary effects of NG11-2 treatment in relation to the development of severe OM during the radiotherapy period.