Drug Shows Promise in Reducing Oral Mucositis in Patients With Head and Neck Cancer

A new drug, GC4419 (Galera Therapeutics), may reduce a common side effect that occurs among 70 percent of patients with head and neck cancer who are being treated with radiation — oral mucositis.

Cancer treatments can break down rapidly dividing epithelial cells that line the gastrointestinal tract, which in turn, leaves the mucosal tissue open to ulceration or infection, also known as mucositis. Because the mucosal tissue that covers the mouth is one of the most sensitive, it makes it even more vulnerable to cancer treatments like chemotherapy and radiation.

Oral mucositis causes pain, the inability to eat which can also lead to nutritional problems, and an increased risk for infection as a result of open sores. In turn, these symptoms can lead to reduced quality of life, chemotherapy or radiation dose-limiting, and increased treatment costs from antibiotics or narcotics or additional or longer hospital stays.

To combat this side effect, Galera Therapeutics created the drug candidate GC4419 for severe oral mucositis, which is currently being evaluated among patients with head and neck cancer.

“Seventy percent of those patients get what is called severe oral mucositis, and that has the immediate and deleterious effect of sores being painful, but it also interferes with eating, and it can cause treatment interruptions. And then there are more chronic effects that occur later on, like dry mouth, xerostomia, and others that can have longer term consequences,” Mel Sorensen, CEO of Galera Therapeutics, said in an interview with CURE.

GC4419 is a first-in-class, small molecule enzyme mimetic that converts superoxide to hydrogen peroxide and molecular oxygen. Sorensen explained that this conversion can be selective among patients being treated with radiation.

“In patients who are getting radiation for cancer treatment, the super oxide is created and it overwhelms the natural system. So, you get a build-up of super oxide in tissues,” he added. “In fact, you get a selective build-up of super oxide tissues in normal tissues. What we can do with our compound, is because we convert it to hydrogen peroxide and the cancer cells are more sensitive to the hydrogen peroxide, there is a build-up of hydrogen peroxide in the cancer cells. So, that is where we get our selectivity.”

In the double blind, placebo-controlled phase 2a trial, researchers randomized 223 patients with head and neck cancer to receive either 30 mg or 90 mg of GC4419 or placebo by infusion on the days they received their radiation treatment. Patients were scheduled to receive seven weeks of radiation therapy plus cisplatin, therefore, the researchers aimed to determine the duration of severe oral mucositis they experienced in this timeframe.

Patients in the placebo arm endured having severe oral mucositis for an average of 19 days, whereas the group of patients who received the 90-mg dose of GC4419 only experienced the side effect for about a day and a half — a 92 percent reduction.

Severe oral mucositis occurred in 58 percent of the placebo arm, but in only 40 percent of patients who received the 30-mg dose and 37 percent of those who received 90 mg.

In addition, patients treated with GC4419 experienced longer delays in the time to onset of oral mucositis, and fewer grade 4 events occurred. The agent was also tolerated and the frequency of treatment-related side effects was comparable across all treatment arms in the trial.

“There are three things about this study that are very important for demonstrating that our technology works,” said Sorensen. “The first is we had a very robust result, highly statistically significant and clinically relevant in the primary endpoint. The second is that all of the secondary endpoints pointed in the same direction, that they were consistent with the primary endpoint. And third is that the intermediate dose, 30 mg, was also intermediate in results between the two arms.”

Sorensen noted these trial results show promise in reducing additional radiation-related toxicities. “This was a demonstration that we could not only selectively reduce the toxicity of radiation, but also preserve the activity of the chemoradiation, in other words, not reduce that against the cancer.”

Therefore, Galera Therapeutics intends to further investigate GC4419 as an agent to treat and reduce, and go after the cancer itself, as well as the side effects, Sorensen said.

“We want to make sure that our plan and our discussion with the FDA results in the most efficient way to get this to patients because after all everything we do is theoretical until we can actually get it to patients, which is what we want to do,” he added.