NEW YORK – Ayala Pharmaceuticals, MD Anderson Cancer Center, and the Adenoid Cystic Carcinoma Research Foundation on Tuesday said they've begun enrolling patients in a trial exploring the activity of Ayala's gamma-secretase inhibitor AL101.
The partners have enrolled five patients with aggressive Notch-activated ACC in the "window of opportunity" trial, which is being funded by the US Department of Defense, the ACC Research Foundation, and Ayala. In the trial, patients who provide a biopsy to confirm they have Notch-activated ACC will receive AL101 for six to eight weeks before they undergo surgery to remove their tumors. Patients can receive AL101 after surgery at the discretion of their doctors.
Researchers are primarily interested in the safety of AL101 and the feasibility of administering the drug in the pre-operative setting. They will also compare NICD1 levels in patients' baseline tumor samples and post-treatment surgical specimens using immunohistochemistry.
Secondary outcomes of interest include objective response rate and the percentage of patients undergoing initial surgery after AL101 therapy. Researchers will also explore whether pre- and post-treatment tumor and blood biomarkers can predict treatment response or the risk of toxicities.
ACC is a rare cancer of the secretory glands that affects approximately 3,400 people in the US each year. Currently, ACC is treated with surgery and radiation, which yields high five-year survival rates. However, ACC patients tend not to respond to chemotherapy, and 60 percent eventually experience disease recurrence after surgical resection.
Jeffrey Kaufman, executive director of the ACC Research Foundation, noted in a statement that there are no approved treatments for patients with recurrent or metastatic disease. Other studies have shown that the Notch pathway, when dysregulated, drives ACC metastasis and is associated with a poor prognosis in patients.
According to Ayala, AL101 monotherapy has demonstrated some efficacy already in advanced, Notch-activated ACC. The latest study may further advance understanding of how Ayala's drug is impacting tumor biology and inform the Israel-based firm's future development strategy for the agent.
"It has been established that mutations in Notch are tumorigenic drivers in ACC and correlate with poorer prognosis," Renata Ferrarotto, director of head and neck oncology clinical research at MD Anderson, said in a statement. "AL101, as a γ-secretase inhibitor, can extinguish Notch signaling in these mutant tumors and has the potential to reduce recurrence and improve long-term patient outcomes."
In January 2021, Ayala began a Phase II trial of AL101 in Notch-activated triple-negative breast cancer patients.