IMGN632 is efficacious with venetoclax plus azacitidine in AML models

Marina Konopleva, MD, PhD, University of Texas MD Anderson Cancer Center, Houston, TX, shares the findings of IMGN632 plus venetoclax and azacitidine triplet therapy efficacy in acute myeloid leukemia models in vitro and in vivo. IMGN632 is a novel antibody-drug conjugate, with an anti-CD123 antibody and a DNA single-stranded break-inducing alkylating payload. AML cells express high levels of CD123, making IMGN632 effective in AML treatment. Given preliminary results of synergy with venetoclax, a BCL-2 inhibitor, IMGN632 was investigated with the established combination of VEN + AZA. Cell line studies identified upregulation of apoptotic proteins and increased cell death with the triplet combination, compared to IMGN632 or VEN+AZA separately. The triplet also showed superior efficacy in AML patient-derived xenograft models. Additionally, in models refractory to the VEN + AZA doublet, the triple combination resulted in efficacy results exceeding those of IMGN632 alone. This indicates synergistic activity of the three agents. The pre-clinical results support the addition of IMGN632 to VEN+AZA, and a Phase Ib clinical trial has begun. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.