SGX942 Decreases Duration of Severe Oral Mucositis in Patients with Head and Neck Cancer

MASCC/ISOO

SGX942 is a novel agent that decreased the incidence of severe oral mucositis (OM) in patients with head and neck cancer (HNC) undergoing chemoradiation (CRT), according to new research led by Oreola Donini, PhD, Senior Vice President and Chief Scientific Officer at Soligenix, Inc, and Mahesh R. Kudrimoti, MD, Professor of Radiation Medicine at the University of Kentucky in Lexington.

They presented the results of this double-blind, placebo-controlled, phase 2 exploratory study in a poster 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. CRT-associated OM has been linked to dysfunctional inflammation stimulated by innate immunity.

Patients with HNC undergoing CRT are at a particularly high risk for ulcerative OM (World Health Organization [WHO] score ≥2) and severe OM (WHO score ≥3), and severe OM can cause the interruption of CRT in addition to negatively impacting the quality of life of these patients.

Study Design

A total of 111 patients with HNC receiving radiation of at least 55 Gy and cisplatin (either weekly at a dose of 30-40 mg/m² or every third week at 80-100 mg/m²) were enrolled in the study. Participants received placebo (n = 43) or SGX942 at either 1.5 mg/kg (n = 41) or 6.0 mg/kg (n = 24) twice weekly with a 4-minute intravenous infusion. A group (n = 3) receiving a dose of 3.0 mg/kg was also included for dose-escalation safety purposes only and was not included in the efficacy analysis. OM was monitored twice weekly until the end of radiation, and then weekly for 1 month. Key efficacy end points included incidence and/or duration of severe OM.

Effective Dose Is 1.5 mg/kg

According to the researchers, participants with a higher incidence of severe OM experienced a greater benefit from SGX942, although a reduced duration of ulcerative OM was also observed. Depending on the type of chemoradiation received, the 1.5-mg/kg dose decreased the duration of severe OM by 50% and 67% among patients at highest risk for it. The drug did not interfere with tumor treatment, with tumor status at the 1-month follow-up visit favoring the 1.5-mg/kg treatment group. Nonfungal infections were also decreased in the patients treated with SGX942.

Findings in the 1.5-mg/kg group were consistent across end points (incidence, onset, and duration of severe OM) and subpopulations (human papilloma­virus negative or positive, chemotherapy type, etc), whereas in comparison, the 6.0-mg/kg dose was found to be less effective and inconsistent. A similar nonlinear dose response curve was observed in the clinical and preclinical phase 1 studies.

The investigators found the treatment drug to be safe and well tolerated in patients with HNC, and no treatment-emergent changes were observed in vital signs, laboratory values, adverse events, or serious adverse events between treatment groups. These findings were consistent with the phase 1 clinical study.

This exploratory study confirmed the effective dose of SGX942 in HNC patients with severe OM, and the results support further clinical research on its effectiveness in OM, the investigators said.

Reference

Donini O, Kudrimoti M, Curtis A, et al. SGX942 reduces the duration of severe oral mucositis. Poster presented at: MASCC/ISOO Annual Meeting on Supportive Care in Cancer; June 23-25, 2016; Adelaide, Australia.

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