The U.S. Food and Drug Administration (FDA) recently granted Breakthrough Therapy designation to LOXO-292, a selective RET inhibitor, for the treatment of patients with advanced RET fusion–positive thyroid cancer who require systemic therapy, have had disease progression following prior treatment, and have no acceptable alternative treatment options. Like two previously granted LOXO-292 Breakthrough Therapy designations announced in September 2018, this additional designation was based on data from the ongoing global phase I/II LIBRETTO-001 clinical trial.
LOXO-292 is an oral, selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities in the rearranged during transfection (RET) kinase. LOXO-292 was designed to inhibit native RET signaling as well as anticipated acquired resistance mechanisms that could otherwise limit the activity of this therapeutic approach.
About RET-Altered Cancers
Genomic alterations in RET kinase, which include fusions and activating point mutations, lead to overactive RET signaling and uncontrolled cell growth. RET fusions have been identified in approximately 2% of non–small cell lung cancers, 10% to 20% of papillary and other thyroid cancers, and a subset of additional cancers.
Activating RET point mutations account for approximately 60% of medullary thyroid cancers. Both RET fusion cancers and RET-mutant medullary thyroid cancers are primarily dependent on this single activated kinase for their proliferation and survival. This dependency, often referred to as oncogene addiction, renders such tumors highly susceptible to small-molecule inhibitors targeting RET.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.