Patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) marked by high expression of CD123 have few effective treatment options. In a new multicenter Phase I/II trial, researchers led by Naval Daver, M.D., and Hagop Kantarjian, M.D., evaluated pivekimab sunirine, a novel CD123-targeting antibody-drug conjugate, in 91 patients with CD123+ R/R AML. This first-in-human dose-escalation and expansion study had a primary endpoint to determine the maximum tolerated dose and the recommended Phase II dose. The recommended dose was selected as 0.045 mg/kg once every three weeks.
At this dose, the overall response rate was 21%, and the composite complete remission rate was 17%. The therapy was well-tolerated with manageable side effects, and patients did not experience capillary leak syndrome or severe myelosuppression, which are common with other CD123 antibody constructs. Pivekimab also is being evaluated as frontline monotherapy for blastic plasmacytoid dendritic cell neoplasm (BPDCN) in the CADENZA study and as a frontline combination with azacitidine and venetoclax in older/unfit patients with AML.