Josh Bilenker, MD
Oncogenic fusions involving TRK proteins have been implicated in various cancer types, prompting clinical development of therapies targeting the aberrations across histologies rather than their body site of origin. This “tumor-agnostic” development approach includes research into next-generation sequencing (NGS) and immunohistochemistry (IHC) assays for the detection of TRK fusions.
Figure. TRK Fusions Found In Diverse Cancer Histologies
Larotrectinib (LOXO-101), a novel small molecule, is the most advanced selective pan-TRK inhibitor in development.1
Updated results demonstrate an 80% response rate by investigator assessment (95% CI, 67%-90%), including 16% complete responses, among 55 evaluable adult and pediatric patients with 17 unique cancer types who were treated with larotrectinib in 1 of 3 phase I/II clinical trials.2 The findings will support a new drug application that Loxo Oncology, which is developing the drug, plans to file with the FDA later this year or early in 2018. Currently, there are 3 modalities for testing for oncogenic mutations or amplifications that have varying potential for use as diagnostics in the TRK space: fluorescence in situ hybridization (FISH), IHC, and NGS.
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