LY3076226 (Drug Description)

LY3076226 is an antibody-drug conjugate or ADC, being developed by Eli Lilly Oncology, is comprised of anti-FGFR-3 (Fibroblast Growth Factor Receptor 3) antibody conjugated to a microtubule inhibitor, DM4, for the treatment of advanced or metastatic cancer.

The investigational drug is currently in  a phase I clinical trial (NCT02529553) for advanced or metastatic cancer (including multiple myeloma and lymphoma), locally advanced, unresectable, or metastatic urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis with locally determined overexpression or alterations in FGFR-3 and advanced or metastatic cancer, including multiple myeloma and lymphoma, with locally determined overexpression or alterations in FGFR-3.

Target
Fibroblast growth factors (FGFs) and their receptors control a wide range of biological functions, regulating cellular proliferation, survival, migration and differentiation. [1] The  growth factor receptor (FGFR) family consists of four members—FGFR-1, FGFR-2, FGFR-3, and FGFR-4—which mediate cellular signaling after binding to their high-affinity ligands, the FGFs. The FGF/FGFR signaling pathway has been shown to mediate cell proliferation, migration, motility, and survival. Autophosphorylation of FGFR is required for activation of FGF-induced downstream signaling. The aberrant regulation of this pathway has been implicated in many forms of human malignancies.[2] It has also been determined that activation of the FGF/FGFR pathway may lead to increased tumor angiogenesis and play a role in tumor resistance to antiangiogenic agents and other chemotherapies.[1][2]


Last Editorial Review: November 13, 2016.