IMGN632 + azacitidine + venetoclax

This agent is a **triplet combination therapy** composed of IMGN632 (pivekimab sunirine), azacitidine, and venetoclax, under clinical investigation for the treatment of relapsed/refractory and frontline CD123-positive acute myeloid leukemia (AML). IMGN632 is a CD123-targeting antibody-drug conjugate (ADC) utilizing a humanized anti-CD123 antibody linked via a cleavable peptide linker to an indolinobenzodiazepine (IGN) class DNA-alkylating cytotoxic payload (pseudodimer). Its mechanism is selective delivery of this cytotoxin to CD123-expressing leukemia cells, leading to DNA alkylation without crosslinking, inducing cytotoxicity, and sparing normal hematopoietic progenitors. Azacitidine is a hypomethylating agent that incorporates into DNA and RNA, impairing DNA methylation and causing cytotoxicity. Venetoclax is a selective inhibitor of B-cell lymphoma 2 (BCL-2), restoring apoptosis in leukemic cells. This triplet is studied in a dose-escalation and expansion Phase 1b/2 trial, specifically in cases of AML where conventional therapies may not be appropriate or have failed, particularly in CD123-positive disease[4][2][3].

Other names

IMGN632 + azacitidine + venetoclaxpivekimab sunirine + azacitidine + venetoclax