The FDA ( U.S. Food and Drug Administration ) has granted Breakthrough Therapy Designation to LOXO-292, a selective RET inhibitor, for: the treatment of patients with metastatic RET-fusion-positive non-small cell lung cancer who require systemic therapy and have progressed following Platinum-based chemotherapy and an anti-PD-1 or anti-PD-L1 therapy; and for the treatment of patients with RET-mutant medullary thyroid cancer who require systemic therapy, have progressed following prior treatment and have no acceptable alternative treatment options.
The LOXO-292 Breakthrough Therapy Designation was based on data from the ongoing global phase 1/2 LIBRETTO-001 clinical trial.
The FDA's Breakthrough Therapy Designation is intended to expedite the development and review of a drug candidate that is planned for use to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.
LOXO-292 is an oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities in the rearranged during transfection ( RET ) kinase.
RET fusions and mutations occur across multiple tumor types with varying frequency. 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.
Genomic alterations in the 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 cancer, 10-20% of papillary and other thyroid cancers, and a subset of other cancers.
Activating RET point mutations account for approximately 60% of medullary thyroid cancer.
Both RET fusion cancers and RET-mutant medullary thyroid cancer 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. ( Xagena )
Source: Loxo Oncology, 2018