CC-95251 + azacitidine + venetoclax

CC-95251 + azacitidine + venetoclax is a combination therapy under investigation primarily for hematologic malignancies, notably acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). CC-95251 is a monoclonal antibody targeting SIRPα, designed to disrupt the "don't eat me" signal mediated by CD47-SIRPα interaction, thus enhancing macrophage-mediated phagocytosis of tumor cells. Azacitidine is a hypomethylating agent that incorporates into DNA and RNA, leading to DNA hypomethylation and direct cytotoxicity. Venetoclax is a small molecule inhibitor of B-cell lymphoma 2 (BCL-2), promoting apoptosis in malignant cells. This combination is being evaluated in early-phase clinical trials, sponsored by Bristol Myers Squibb (formerly Celgene), for treatment of AML and MDS.[2][4][6][8]