CC-95251 + azacitidine

CC-95251 + azacitidine is an investigational combination therapy comprising CC-95251, a fully human monoclonal antibody that targets signal regulatory protein alpha (SIRPα), and azacitidine, a hypomethylating antineoplastic agent. CC-95251 blocks the SIRPα–CD47 interaction on myeloid cells, allowing macrophage-mediated phagocytosis of tumor cells, which is a new immune checkpoint approach for treating hematological malignancies, such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Azacitidine induces pro-phagocytic signals and direct cytotoxicity by incorporating into DNA and RNA and inhibiting DNA methyltransferase, thereby altering gene expression and promoting cytotoxicity in malignant cells. The combination aims to enhance anti-leukemic efficacy through synergistic mechanisms involving both enhanced phagocytosis of malignant cells and cytotoxic effects. The combination is being studied in adult patients with AML and MDS, including untreated and relapsed/refractory settings[1][3][4][6].