LY4052031

LY4052031 is a next-generation antibody-drug conjugate (ADC) developed by Eli Lilly. It targets Nectin-4, a cell surface protein overexpressed in several solid tumors including urothelial, breast, lung, ovarian, and cervical cancers. The drug consists of a fully human IgG1 Fc-silent monoclonal antibody against Nectin-4 conjugated via a cleavable peptide linker to a novel camptothecin-based topoisomerase I inhibitor payload (camp98/LSN3889710), with a homogeneous drug-antibody ratio (DAR) of 8:1. This design aims to deliver potent cytotoxic activity specifically to Nectin-4-expressing tumor cells while sparing normal tissues that express low levels of the antigen. Preclinical studies have shown robust antitumor efficacy across various models—including those resistant to MMAE-based ADCs like enfortumab vedotin—demonstrating both direct cytotoxicity and bystander killing effects. As of mid-2025, LY4052031 has been evaluated in global phase 1 clinical trials for advanced or metastatic urothelial carcinoma and other select solid tumors[1][4][5][6][7].