by Dr. C.H. Weaver M.D. 6/2018
Loxo Oncology presented at the American Society of Clinical Oncology annual meeting in Chicago the initial clinical trial data for LOXO-292, a novel precision cancer medicine targeting tumors containing a mutated protein known as RET.
LOXO-292 is an oral precision cancer medicine that is designed to target cancers with genomic alterations in the RET kinase, which include fusions and activating point mutations which lead to overactive RET signaling and uncontrolled cell growth. These “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. 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.
In the current clinical trial LOXO-292 shrank the cancer in 77% of patients with RET fusion cancers originating in the lungs, thyroid and pancreas. Overall treatment with LOXO-292 was well tolerated. According to the investigators the anti-cancer responses to LOXO-292 have been durable. None of the responding patients has relapsed to date, with the longest-followed patient still on therapy 10 months since beginning treatment.
LOXO-292 is currently only available in clinical trials but represents a new area of development for precision cancer medicine. Loxo’s other medicine in development is larotrectinib which has already demonstrated significant anti-cancer activity in cancers with TRK gene fusions. The drug is under FDA review with an approval decision expected in late November.