Adelaide, Australia—SGX942, a novel agent that is first in its class, decreased the incidence of severe oral mucositis in patients with head and neck cancer undergoing chemoradiation, according to new research led by Oreola Donini, PhD, Senior Vice President and Chief Scientific Officer, Soligenix, Princeton, NJ, and Mahesh R. Kudrimoti, MD, Professor of Radiation Medicine, University of Kentucky, Lexington.
They presented the results of this double-blind, placebo-controlled, phase 2 exploratory study at the 2016 Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology Annual Meeting on Supportive Care in Cancer.
SGX942 is a first-in-class innate defense regulator containing the active ingredient dusquetide. According to Dr Donini, its novel mechanism of action modulates the innate immune system to decrease inflammation and enhance bacterial clearance and tissue healing. Chemoradiation-associated oral mucositis has been linked to dysfunctional inflammation stimulated by innate immunity.
Patients with head and neck cancer undergoing chemoradiation are at a particularly high risk for ulcerative (World Health Organization [WHO] score ≥2) and severe (WHO score ≥3) oral mucositis, and severe oral mucositis can cause the interruption of chemoradiation in addition to negatively impacting the quality of life of these patients.
A total of 111 patients with head and neck cancer receiving ≥55 Gy radiation and cisplatin (at a dose of 30-40 mg/m2 weekly or 80-100 mg/m2 every third week) were enrolled in the study. Participants received placebo (n = 43) or SGX942 1.5 mg/kg (n = 41) or 6.0 mg/kg (n = 24) twice weekly with a 4-minute intravenous infusion. Oral mucositis was monitored twice weekly until the end of radiation, and then weekly for 1 month. Key efficacy end points included incidence and duration of severe oral mucositis.
An Effective Dose
Patients with higher incidence of severe oral mucositis had a greater benefit from SGX942, although a reduced duration of ulcerative oral mucositis was also observed. Depending on the type of chemoradiation received, the 1.5-mg/kg dose decreased the duration of severe oral mucositis by 50% and 67% among patients at highest risk. The drug did not interfere with tumor treatment, and tumor status at the 1-month follow-up visit favored the 1.5-mg/kg treatment group. Nonfungal infections also decreased in the patients receiving SGX942.
Findings in the 1.5-mg/kg group were consistent across end points (ie, incidence, onset, and duration of severe oral mucositis) and subpopulations (eg, human papillomavirus negative or positive, chemotherapy type): in comparison, the 6.0-mg/kg dose was less effective and inconsistent. A similar, nonlinear dose response curve was observed in the clinical and preclinical phase 1 studies.
The investigators found the drug to be safe and well-tolerated among patients with head and neck cancer, and no treatment-emergent changes were observed in vital signs, laboratory values, adverse events, or serious adverse events between the treatment groups. The findings were consistent with those of the phase 1 clinical study.
This exploratory study confirmed the effective dose of SGX942 in patients with head and neck cancer who have severe oral mucositis, but these results support further clinical research on its effectiveness in oral mucositis, the investigators said.