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Treatment with the small molecule oral immunomodulator EC-18 resulted in a reduction in both the duration and incidence of severe oral mucositis in patients with head and neck cancer who are undergoing concurrent chemoradiation.
Treatment with the small molecule oral immunomodulator EC-18 resulted in a reduction in both the duration and incidence of severe oral mucositis (SOM) in patients with head and neck cancer who are undergoing concurrent chemoradiation, meeting both primary and secondary end points of the phase 2 CRIOM study (NCT03200340).1
With a short-term follow-up period, EC-18 reduced the duration of SOM from 13.5 days to 0 days, translating to an 100% reduction vs placebo. The incidence of SOM through completion of radiation was also reduced with EC-18 by 37.1% vs placebo. The rate of SOM was 65% in the control arm vs 40.9% in the investigative arm.
Moreover, the incidence of SOM through a short-term follow-up period was reduced by 35.1% vs the placebo arm; these rates were 70.0% vs 45.5% in the control and investigative arms, respectively.
Regarding safety, no serious toxicities were observed between the 2 treatment arms; no serious effects were determined to be associated with the investigative agent. Safety findings were similar between the arms, and all toxicities aligned with what is typically reported with chemoradiation.
Follow-up for tumor outcomes is ongoing, according to Enzychem Lifesciences, the drug developer.
“Severe chemoradiation-induced oral mucositis [CROIM] affects almost 75% of patients being treated with concomitant chemoradiation for head and neck cancers with symptoms that are so severe that they challenge a patients’ ability to tolerate optimal treatment,” Stephen Sonis, DMD, DMSc, professor at Harvard School of Dental Medicine and key advisor for the CRIOM study, stated in a press release. “Despite its frequency and burden it places on patients and their caregivers, there is no approved pharmaceutical intervention. The results observed with EC-18 support its continued development and offer encouragement as an effective CRIOM therapy.”
The phase 2 study enrolled patients who were aged 18 years or older, who had pathologically confirmed diagnosis of squamous cell carcinoma of the mouth, oropharynx, hypopharynx, or nasopharynx.2 To be eligible for enrollment, patients needed to have an ECOG performance status of 0 or 1 and have been planned to receive concomitant single-agent chemotherapy in the form of cisplatin either weekly or every 3 weeks.
Patients also had to have been slated to receive intensity-modulated radiation therapy with daily fractions ranging from 2.0 Gy to 2.2 Gy, to a cumulative dose of at least 60 Gy, and a maximum dose of 72 Gy. Radiation fields needed to include at least 2 mucositis sites at risk and both sites needed to receive a minimum of 55 Gy.
If patients previously received radiation treatment to the head and neck, had metastatic disease, active infectious disease apart from oral candidiasis, oral mucositis or any oral lesion that would confound the evaluation of oral mucositis, active systemic disease known to impact the risk or course of oral mucositis, or they received an investigational agent within 30 days of their first dose of radiation, they were excluded.
In the first stage of the study, a total of 24 patients were randomized to receive placebo or EC-18 at 1 of the following 3 doses: 500 mg, 1000 mg, or 2000 mg. In stage 2 of the research, 81 participants were randomized to either placebo or EC-18 at a twice-daily dose of 2000 mg over approximately 7 weeks.
Based on the phase 2 findings, the company has shared plans to file for a breakthrough therapy designation with the FDA later in 2021 and to further explore the investigational agent as part of a global phase 3 trial.
“We are delighted to announce these positive results from our phase 2 US study, which confirm that EC-18 is safe and well-tolerated,” Ki-Young Sohn, chief executive officer and chairman at Enzychem Lifesciences, stated in a press release. “In addition, EC-18 may have a number of key advantages, including oral route of administration and convenience of use. We are excited to advance this novel candidate into a pivotal study and will also evaluate EC-18 for other radiation-induced inflammatory diseases.”