Nicholas Short, MD, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, discusses a Phase II trial (NCT04266795) of a pevonedistat, venetoclax (Ven) and azacitadine (aza) triplet combination in newly-diagnosed acute myeloid leukemia (AML) patients unfit for intensive chemotherapy. Pevonedistat inhibits NEDD8-activating enzyme (NAE), causing cell cycle disturbance and cell death in cancers. Both pevonedistat and Ven, a BCL-2 inhibitor, have been shown to improve survival when combined with aza, compared to aza alone. Additionally, pevonedistat plus Ven has shown synergistic cytotoxic activity in pre-clinical AML data, potentially by preventing MCL-1-mediated Ven resistance. This evidence all together provides the basis for trialling the triplet combination, in the hopes of improving response duration and relapse rates. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.
Consulting fees: Takeda Oncology, AstraZeneca Research funding: Takeda Oncology, Astellas Pharma Inc. Honoraria: Amgen