New RET inhibitor showed 77% overall response rate for RET fusion-positive cases.
Loxo Oncology is focused on the development of highly selective drugs for the treatment of genomic-derived cancers. The company leverages a combination of genomic testing for the identification of defects that lead to cancer and advances in chemistry that enable the production of complex drug candidates. According to Loxo’s CEO Joshua H. Bilenker, genetic sequencing has allowed Loxo to identify the specific mutations that lead to cancers, unveiling targets for specially designed treatments. It is also “becoming a mainstay of clinical practice” and helping physicians to determine the best therapies for each individual patient and his/her cancer type.
The company’s lead compound is larotrectinib, an oral and selective inhibitor of tropomyosin receptor kinases (TRK), a family of signaling proteins that play an important role in cellular communication and tumor growth. In some people, the NTRK genes that encode for TRKs are fused to other genes, resulting in the production of aberrant growth signals that lead to cancer. Larotrectinib is designed to selectively inhibit TRK, preventing the release of the signals without affecting other signaling pathways. The US Food and Drug Administration (FDA) has granted larotrectinib orphan drug, rare pediatric disease and breakthrough therapy designations, as well as priority review, for a variety of cancers.
At the recent ASCO meeting, Loxo reported initial results for its second developmental targeted cancer treatment LOXO-292, an oral, selective inhibitor for the treatment of patients with cancers that harbor abnormalities in the rearranged during transfection (RET) kinase.
A transmembrane receptor tyrosine kinase, RET kinase signaling activates cellular proliferation, survival, invasion, and migration pathways in a tightly regulated way during the development and maintenance of a broad range of tissues, including neural and genitourinary tissues. The RET proto-oncogene can experience alterations, such as RET rearrangements that lead to RET fusions and activating point mutations, that can lead to the formation and spreading of many different types of tumors due to overactive or constitutively active RET activity.
LOXO-292 achieved a 77% overall response rate for RET fusion-positive cases, which was above the predicted 69% value, and 45% in RET-mutant medullary thyroid cancer. Most of the patients in the early clinical study had non-small cell lung cancer, but some had thyroid or pancreatic cancer. Most of the patients in the study were previously treated with a kinase inhibitor and systemic therapy, so achieving this level of response is quite notable, according to Loxo chief business officer Jake Van Naarden.