nadunolimab + azacitidine + venetoclax

CAN04 + azacitidine + venetoclax is an investigational combination regimen being evaluated for the treatment of hematological malignancies, specifically adverse-risk relapsed or refractory (R/R) acute myeloid leukemia (AML). The regimen combines nadunolimab (CAN04), a fully humanized IgG1 monoclonal antibody targeting interleukin-1 receptor accessory protein (IL1RAP), with the hypomethylating agent azacitidine and the BCL-2 inhibitor venetoclax. Nadunolimab binds to IL1RAP on leukemia stem cells and bulk blasts, blocking IL-1α and IL-1β signaling to disrupt the immunosuppressive tumor microenvironment and reverse chemotherapy resistance, while also inducing antibody-dependent cellular cytotoxicity (ADCC). Azacitidine acts as a pyrimidine nucleoside analogue that inhibits DNA methyltransferases, leading to DNA hypomethylation and cellular cytotoxicity, while venetoclax selectively inhibits the anti-apoptotic protein BCL-2 to trigger apoptosis in leukemia cells. This triplet combination is being evaluated in an investigator-initiated Phase 1b/2a clinical trial led by the MD Anderson Cancer Center, with funding support from the U.S. Department of Defense, aiming to target leukemia stem cells and overcome resistance mechanisms in difficult-to-treat myeloid malignancies.

Other names

CAN04 + azacitidine + venetoclaxnadunolimab + azacitidine + venetoclax