Chugai Pharmaceutical Phase 1 trial: AQUA07 in Patients With ALK-Positive Non-Small Cell Lung Cancer; soon to be recruiting
Chugai Pharmaceutical, a major Japanese pharmaceutical company and the early developer of alectinib, will soon be testing AQUA07, an experimental ALK therapy in a Phase 1 trial NCT07617337.
Approved ALK inhibitors are tyrosine kinase inhibitors (TKIs) and occupy the ATP-binding pocket, blocking ATP, the cell’s main energy-carrying molecule, from activating ALK. AQUA07 is designed to bind to a separate allosteric site on ALK. Allosteric refers to the regulation of a protein or enzyme by binding at a site other than the active site, causing a shape change that turns the protein’s activity up or down. This can alter the protein’s three-dimensional conformation, i.e. the shape and molecular movements that determine how the protein functions. It is intended to effectively lock ALK into a state in which it cannot efficiently transmit cancer-promoting signals. Because the binding site is different from the ATP pocket, an allosteric inhibitor may be able to overcome resistance mutations that develop to ALK TKIs, including potentially compound resistance mutations.
AQUA07 is an orally-administered, macrocyclic peptide, a small, ring-shaped molecule designed to bind tightly to its target protein. The ring shape can make the molecule more stable and help it bind to protein surfaces that conventional small-molecule drugs may have difficulty targeting.
The trial is evaluating AQUA07 alone and in combination with lorlatinib, with the initial goals of establishing safety, dosing, and pharmacology while looking for early evidence of anti-cancer activity. ALK trial participants must have been previously treated with at least one ALK TKI regardless of prior chemotherapy treatment. While the trial is posted on clinicaltrials.gov, it is not yet recruiting, although we know that Dana-Farber Cancer Institute will be one site. Chugai Pharmaceutical is a member of the Roche group of companies, headquartered in Basel, Switzerland.
Editor’s Note: Thanks to Dr. Alice Shaw, MD, PhD, Chair of the Department of Medical Oncology and the Chief of Strategic Partnerships at Dana-Farber Cancer Institute, for reviewing this article.
View Full Trial Details on ClinicalTrials.gov
Clinical trial details may change. Please refer to ClinicalTrials.gov for the most up-to-date information.
Jeffrey M. Sturm BS, MA, MBA
ALK Positive, Inc. www.alkpositive.org
Member, Medical Committees
Member Board of Directors
Eleven-year ALK NSCLC survivor
