Dr. Ailawadhi on the Rationale for Evaluating Lisaftoclax in CLL

Sikander Ailawadhi, MD, professor of medicine, consultant, Division of Hematology/Oncology, Department of Internal Medicine, consultant, Department of Cancer Biology, lead, International Cancer Center, Mayo Clinic, discusses the rationale for evaluating lisaftoclax (APG-2575) in chronic lymphocytic leukemia (CLL) in an early phase 1 study (NCT03537482).

Venetoclax (Venclexta), a first-generation BCL-2 inhibitor, is FDA approved for the treatment of several lymphoid and myeloid malignancies, including CLL.The rationale for the phase 1 trial was to continue exploring the role of BCL-2 inhibitors in CLL with the next-generation agent lisaftoclax, Ailawadhi explains. Lisaftoclax was hypothesized to be more refined, more active, and better tolerated compared with venetoclax in this patient population, Ailawadhi says. 

Lisaftoclax has a distinct pharmacokinetic and pharmacodynamic profile in which it affects but does not irreversibly bind to BCL-2 to cause prolonged adverse effects, Ailawadhi adds. Overall, lisaftoclax demonstrated similarefficacy to venetoclax with a different, safer toxicity profile, Ailawadhi concludes.