December 23, 2020 — Although SGX942 was found to induce clinically meaningful reductions in severe oral mucositis vs placebo in patients with head and neck cancer, the benefit failed to reach statistical significance, thus missing the primary end point of the phase 3 DOM-INNATE study.
Although SGX942 was found to induce clinically meaningful reductions in severe oral mucositis (SOM) vs placebo in patients with head and neck cancer, the benefit failed to reach statistical significance, thus missing the primary end point of the phase 3 DOM-INNATE study (NCT03237325).1
Topline data from the trial showed that the primary end point of median duration of SOM did not meet the prespecified criterion for statistical significance (P ≤ .05). However, SGX942 was found to have reduced the median duration of SOM by 56% in this patient population vs placebo. Specifically, the median duration of SOM was 18 days in the placebo cohort vs just 8 days in the investigative cohort.
In the per-protocol population, which was defined as those who had been administered a minimum of 55 Gy of radiation and at least 10 doses of study treatment throughout the intended treatment period, SGX942 reduced the duration of SOM by 50%; this reduction was determined to be statistically significant.
Moreover, in the placebo and investigative arms, the median duration of SOM was 18 days vs 9 days (P = .049). SGX942 also led to a 16% reduction in the incidence of SOM vs placebo in this population.
“We are obviously very disappointed with the unanticipated outcome of the study,” Christopher J. Schaber, PhD, president and chief executive officer of Soligenix, stated in a press release. “Despite the fact that SGX92 demonstrated clinically meaningful reduction in oral mucositis consistent with the phase 2 study, the phase 3 trial did not achieve the statistically significant benefit we expected.”
The active ingredient in SGX92 is dusquetide, which is an innate defense regulator; this has a mechanism of action that allows it to regulate how the body responds to injury and infection, prompting it to produce a response that is anti-inflammatory, anti-infective, and heals tissue. Although this class of short, synthetic peptides does not possess any direct antibiotic activity, it has the potential to improve survival following infections associated with bacterial Gram-positive and-negative pathogens through its novel mechanism of action.
The multinational, placebo-controlled phase 3 trial enrolled a total of 268 participants with squamous cell carcinoma of the oral cavity and oropharynx who had been slated to receive a minimum total cumulative radiation dose ranging from 80 mg/m2 and 100 mg/m2 every third week.
Patients were randomized to receive SGX942 or placebo at a dose of 1.5 mg/kg; this was administered twice weekly during, and for 2 weeks following, the completion of chemoradiation.
Previously, in August 2019, an independent data monitoring committee (DMC) completed a prospectively defined interim analysis of the trial; this review had been used to confirm the underlying assumptions that described the required sample size needed for the study to support its 90% statistical power.2 Because the DMC determined that SGX942 showcased benefit, the target sample size for the study was subsequently adjusted from 190 patients to 260.
Data from the phase 2 trial evaluating the agent did show a significant reduction in the median duration of severe oral mucositis vs placebo in this patient population.3 At 12 months, the findings indicated that SGX942, given at a dose of 1.5 mg/kg, led to accelerated tumor resolution and reduced mortality vs placebo following completion of chemoradiation treatment (P = .08). The safety and tolerability of the drug was also further supported by these findings.
“Over the coming weeks, we will be analyzing the data to better determine why the study did not meet expectations,” added Schaber. “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.”