lisaftoclax + acalabrutinib

Lisaftoclax + acalabrutinib is an investigational oral combination therapy consisting of the selective Bcl-2 inhibitor lisaftoclax (APG-2575) and the Bruton tyrosine kinase (BTK) inhibitor acalabrutinib. Lisaftoclax is being developed as a next-generation Bcl-2 inhibitor, able to induce apoptosis in B-cell malignancies by blocking Bcl-2, a key protein that prevents cancer cell death. It is characterized by a short half-life and is notable for allowing a rapid (five-day) dose ramp-up, unlike venetoclax. Acalabrutinib is a highly selective, covalent BTK inhibitor that interferes with B-cell receptor signaling, reducing malignant B-cell proliferation and survival. The combination has demonstrated a high overall response rate (~96-98%) and favorable safety in phase 1b/2 trials in patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), including those previously treated with venetoclax. No significant drug-drug interactions or unexpected safety signals have been reported. A global phase 3 registrational study (GLORA) in CLL/SLL is underway.