561TiP A phase I dose-escalation study of ZN-d5, an BCL-2 inhibitor with improved selectivity, in patients with advanced non-Hodgkin lymphoma (NHL) or acute myeloid leukemia (AML)

Abstract

Anti-apoptotic proteins such as B-cell lymphoma 2 (BCL-2) are commonly utilized by malignant cells to evade signals that would typically induce programmed cell death. High BCL-2 expression is correlated with poor prognosis and poor responses to conventional therapies in patients with a broad range of malignancies, and dependence on BCL-2 can render cancer cells susceptible to therapy targeting this pathway. ZN-d5 is a novel, oral, once-daily BH3 mimetic with improved selectivity for BCL-2 over BCL-xL compared to the commercially available BCL-2 inhibitor venetoclax, which could reduce the rate of thrombocytopenia.