Fig. 1

DLL3-targeted investigational products utilize distinct mechanisms of action. a Rovalpituzumab tesirine is a DLL3-targeted antibody-drug conjugate (ADC) that consists of a humanized DLL3-specific IgG1 monoclonal antibody, a pyrrolobenzodiazepine (PDB) dimer toxin, and a protease-cleavable linker that covalently links the antibody to the toxin. Internalization of the ADC to lysosomes leads to the cleavage of the linker, release of the toxin, and apoptosis. b AMG 757 is a half-life extended bispecific T cell engager (HLE BiTE®) antibody construct that consists of a single-chain (sc) Fv domain that binds DLL3, an scFv domain that binds CD3ε (an invariable part of the T cell receptor complex), and a fragment crystallizable (Fc) region. AMG 757 is designed to transiently connect DLL3-positive cells to CD3-positive T cells and induce serial lysis of tumor cells and concomitant proliferation of T cells. c AMG 119 is an adoptive cellular therapy that consists of a patient’s own T cells that have been genetically modified ex vivo to express a chimeric antigen receptor (CAR) that targets DLL3 and redirects cytotoxic T cells to DLL3-positive cells. AMG 119 is designed to expand and persist in vivo and induce apoptosis of tumor cells