Phase 2/3 Pivekimab sunirine CD123-targeted ADC (IGN payload) + venetoclax/azacitidine in AML

AbbVie’s randomized Phase 2/3 trial (NCT07581002) tests whether adding pivekimab sunirine (PVEK)—a CD123-directed monoclonal antibody–drug conjugate carrying an indolinobenzodiazepine (IGN) DNA-alkylating payload—can improve outcomes versus venetoclax plus azacitidine alone in newly diagnosed AML patients who are ineligible for intensive chemotherapy and have CD123-positive disease. Phase 2 is open-label and randomized (PVEK+VEN+AZA vs VEN+AZA), while Phase 3 is double-blind and randomized (PVEK+VEN+AZA vs placebo+VEN+AZA), aiming to confirm benefit while controlling for expectation and management bias. Venetoclax (AbbVie/Genentech-Roche) inhibits BCL-2 to promote apoptosis, and azacitidine (a hypomethylating agent) reprograms aberrant DNA methylation and supports cytotoxicity in AML. CD123 is commonly expressed on AML blasts and leukemic stem/progenitor cells, making it an attractive target to “deliver” a potent payload into malignant cells; the commercial angle is a potential registrational path for a CD123 ADC layered onto the dominant lower-intensity backbone. Today, many older/unfit newly diagnosed AML patients receive venetoclax + azacitidine as frontline therapy, with relapse often managed by switching therapies (including targeted inhibitors when mutations allow) or moving to transplant in select responders—this study asks whether intensifying the same backbone with a targeted ADC can deepen and extend remissions.