Dusquetide Improves Severe Oral Mucositis, But Misses Statistical Significance in Head and Neck Cancers

Biological activity was observed with dusquetide (SGX942) as treatment of severe oral mucositis (SOM) in patients with head and neck cancer receiving chemoradiation with a 56% reduction in the median duration of SOM from 18 days in the placebo arm to 8 days with the study drug, in the pivotal phase 3 DOM-INNATE study (NCT03237325). However, according to preliminary topline findings announced by Soligenix, developer of the drug, in a press release, the difference was not found to be statistically significant.

The pre-specified criterion for statistical significance for the primary end point of median duration of SOM was not achieved (P ≤. 05), and the variability in the distribution of these findings yielded a P value that was not statistically significant, despite the clinically meaningful improvement observed.

"Despite the fact that SGX942 demonstrated clinically meaningful reductions in oral mucositis consistent with the phase 2 study, the phase 3 trial did not achieve the statistically significant benefit we expected. Over the coming weeks, we will be analyzing the data to better determine why the study did not meet expectations. If there is any clarity gained from further analysis of the dataset, especially with respect to specific subsets of patients that may benefit from SGX942 therapy, we will certainly communicate our findings and explore follow-up discussions with the FDA and the European Medicines Agency,” said Christopher J. Schaber, PhD, president and CEO of Soligenix, in a statement.

Other secondary end points that support the biological activity include a statistically significant reduction of 50% in the duration of SOM in the per-protocol population, which was defined as the population of patients receiving at least 55 Gy radiation and at least 10 doses of dusquetide or placebo. The duration of SOM in this group decreased from 18 days in the placebo arm to 9 days with dusquetide (P = .049), and this is consistent with the findings from the phase 2 study.

The incidence of SOM also supported this biological trend, which was decreased 16% in the experimental arm relative to the placebo arm in the per-protocol population. There were no major protocol deviations on the study, such as extended breaks longer than 8 days between successive doses of treatment.

Findings from an interim analysis conducted in August 2019, resulted in the recommended addition of 35 patients to maintain 90% power, and the patients are being followed for an additional 12 months following completion of the study treatment.

SOM is estimated to affect approximately 90,000 patients in the United States, with comparable estimates in Europe as well. It occurs in almost all patients with head and neck cancer who are treated with chemoradiation, and it tends to be severe, which causes an inability to eat and/or drink for >80% of patients. Occurring in 40% to 100% of cases, SOM is common in patients receiving high-dose chemotherapy and undergoing hematopoietic stem cell transplantation, and the incidence and severity depend greatly on the nature of conditioning therapy that is used for myeloablation.

With no currently approved therapies available in the context of any solid tissue tumors, SOM represents an area of unmet medical need.

The multinational, placebo-controlled, randomized clinical trial enrolled 268 patients with a diagnosis of squamous cell carcinoma of the oral cavity and oropharynx who were scheduled to receive a minimum of 55 Gy fractionated radiation at 2.0 to 2.2 Gy per day, in addition to concomitant cisplatin at 80 to 100 mg/m2 every 3 weeks. Patients were randomized to receive a dose of 1.5 mg/kg dusquetide or placebo twice per week during chemoradiation therapy and for 2 weeks following completion of chemoradiation.

Oral mucositis is evaluated with the World Health Organization (WHO) Grading system, and SOM is defined as a WHO grade ≥3.

Patients were excluded from the study if they had current mucositis, current clinically significant active infection that would make them unfit for the study, plans to receive cetuximab (Erbitux) or a similar targeted agent between baseline and 6 weeks following radiation therapy, or prior radiation to the head and neck. Patients were also ineligible if they had chemotherapy within the last 12 months or tumors of the lips, sinuses, glands, nasopharynx, hypopharynx, or larynx.

_Reference

_{Soligenix announces topline results from its phase 3 clinical trial of SGX942 for the treatment of oral mucositis in head and neck cancer patients. News Release. Soligenix Inc. December 22, 2020. Accessed December 23, 2020. https://bit.ly/34A5XMo}