Phase 2 Clinical Trial at Sylvester Studies First-in-class Drug for Head and Neck Cancers

Clinical researchers at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine and the Veterans Administration Greater Los Angeles health system have initiated a phase 2 clinical trial for an investigational drug as an induction (first) therapy against head and neck cancers (HNCs).

Elizabeth Franzmann, M.D.
Elizabeth Franzmann, M.D., a head and neck surgeon at Sylvester and professor of otolaryngology at the Miller School, will lead the UM arm of the trial.

The drug, called APG-157, will be administered before surgery and other definitive treatments to newly diagnosed, locally advanced patients (stage 0-4). The drug modulates the tumor microenvironment and is intended to reduce the tumor burden, to lessen the need for extensive surgical resection and intensive therapies. Currently, there is no specific induction therapy drug approved by the FDA for patients at this stage of cancer, and existing repurposed chemotherapies have significant toxicities.

“We are trying to find better approaches so we don’t have to deliver such toxic anti-cancer treatments,” said Elizabeth Franzmann, M.D., a head and neck surgeon at Sylvester and professor of otolaryngology at the Miller School, who will lead the UM arm of the trial. “We hope to decrease the amount of radiation, avoid chemotherapy, or perform smaller surgeries, decreasing the negative effects of treatment and preserve the organs.”

HNCs are among the most common and difficult cancers to treat. Approximately 476,000 people are diagnosed with cancer of the oral cavity and oropharynx (throat) worldwide, and around 225,000 people die from this disease each year.

‘Window of Opportunity’ Trial

While most cancer studies combine the trial drug with standard of care therapies, this is a “window of opportunity” trial, in which patients will receive APG-157 four to six weeks before receiving other treatments.

“If patients need surgery in two weeks, they probably won’t be eligible for this study,” said Dr. Franzmann. “But usually, there’s a gap between when a patient is diagnosed and when we can actually do their surgery or start their treatments, providing this window for induction therapy.”

APG-157, which was developed by Aveta Biomics, is a novel drug on several levels. It is a multi-agent, multi-targeted drug derived from the plant Curcuma longa. The safety and anti-cancer properties of the plant and its principal molecule, curcumin, are well established. Pilot data suggests that the drug induces selective cancer cell death, activates the immune system, and modulates the dysbiosis of oral microbiome in cancer patients.

Dr. Franzmann examining a patient.
“We are trying to find better approaches so we don’t have to deliver such toxic anti-cancer treatments,” Dr. Franzmann said.

“Unlike existing drugs for head and neck cancer, APG-157 is a first-of-its-kind drug that is delivered in a form of a pastille that dissolves in the mouth, thus significantly increasing ease of administration,” said Luis Z. Avila, Ph.D., Aveta’s vice president of research and development. “As a result, the drug acts both topically and through systemic absorption, and has high bioavailability. We are very hopeful that it will offer oncologists the first new drug in a long time to help these patients up front.”

Studying Efficacy, Biomarkers

The study will recruit 24 patients with oral cavity or oropharynx cancer at both trial sites to investigate the drug’s safety and ability to reduce tumors, as well as measure cancer stem cell biomarkers to track tumor activity. The researchers will also test whether oral cavity and oropharynx cancer patients have different responses.

“One of our goals in this phase 2 trial is to provide data that will help design a pivotal or a phase 3 study,” said Dr. Franzmann. “In particular, it will help us refine the inclusion and exclusion criteria and identify a high-responder cohort.”

Following APG-157 treatment, the research team will compare the initial biopsies with tumor tissue removed later to measure the drug’s therapeutic impact, investigating tumor size and cellular and molecular biomarkers.

“I’m really excited about this study.” said Dr. Franzmann. “If it proves to be well tolerated and easy to take, and if it shrinks tumors, it could help decrease the toxicity that oral and oropharyngeal cancer patients experience with current treatments, and improve outcomes.”

Tags: APG-157, Aveta Biomics, Department of Otolaryngology, Dr. Elizabeth Franzmann, head and neck cancers, induction therapy, Miller School of Medicine, phase 2 clinical trial, Sylvester Comprehensive Cancer Center