VA Clinical Trial of a Naturally-Derived Drug Lozenge Shows Promising Results and Safety in Combating Oral Cancer

The drug, called APG-157, comes in the form of a lozenge delivered orally. In contrast currently used Head & Neck Cancer drugs are delivered intravenously. The drug is derived from the plant Curcuma longa, a source of common spice Turmeric.  It is administered before surgery and other definitive treatments to newly diagnosed, locally advanced patients (stage 1-4) with oral or oropharyngeal (throat) cancer. The drug modifies the tumor and has shown to reduce it, thus lessening the need for extensive surgery and intensive therapies.   

Currently, there is no specific induction therapy drug approved by the FDA for patients at this stage of cancer, and existing chemotherapies have significant toxicities. 

“Oral cancer affects the tongue, mouth, and throat. It’s common in people who smoke or have the human papillomavirus (HPV),” said VA surgeon and researcher Dr. Marilene Wang. “As you can imagine, surgery of the mouth or tongue is painful, and the recovery is long. We found APG-157 to shrink small oral tumors and possibly stabilize the growth of large ones. With smaller tumors, the amount of radiation or chemotherapy can be reduced, or smaller surgeries performed.”   

Head and neck cancers are among the most 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. 

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. 

APG-157, which was developed by Aveta Biomics, is a novel drug on several levels. It is the  first multi-agent, multi-targeted drug for Head & Neck Cancer. The safety and anti-cancer properties of the plant and its principal molecules, zinflavonoids, are well established. Pilot data suggest that the drug induces selective cancer cell death, activates the immune system, and modulates the dysbiosis of the oral microbiome in cancer patients. 

“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 lozenge 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.” Aveta Biomics, Inc. manufactures the drug.

 
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. Wang.  

Research scientist, Dr. Saroj Basak, is the clinical coordinator for the project, and basic research scientist Dr. Eri Srivatsan is the co-principal investigator and is involved in identifying the molecular mechanism of APG-157’s effects on tumor cell growth suppression. 

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

If you have any questions, please contact the VA Greater Los Angeles Public Affairs Office at  VHAGLAPublicAffairs@va.gov or call 310-268-3340.