Larotrectinib is being investigated to potentially treat adult and pediatric patients with locally advanced or metastatic solid tumors with a neurotrophic tyrosine receptor kinase ( NTRK ) gene fusion.
Larotrectinib has demonstrated clinical responses in patients with NTRK fusion cancer across various tumor types in both children and adults.
Loxo Oncology and Bayer are engaged in a collaboration for the development and commercialization of Larotrectinib.
Larotrectinib is an oral and selective investigational tropomyosin receptor kinase ( TRK ) inhibitor in clinical development for the treatment of patients with cancers that harbor a neurotrophic tyrosine receptor kinase ( NTRK ) gene fusion.
Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body.
In clinical trials, Larotrectinib has demonstrated anti-tumor activity in patients with tumors harboring NTRK gene fusions, regardless of patient age or tumor type.
In an analysis of 55 RECIST-evaluable adult and pediatric patients with NTRK gene fusions, using a July 17, 2017 data cutoff, Larotrectinib has demonstrated a 75% centrally-assessed confirmed overall response rate ( ORR ) and an 80% investigator-assessed confirmed ORR, across many different types of solid tumors.
The majority ( 93% ) of all adverse events were grade 1 or 2.
TRK fusion cancer occurs when a neurotrophic tyrosine receptor kinase ( NTRK ) gene fuses with another unrelated gene, producing an altered tropomyosin receptor kinase ( TRK ) protein.
The altered protein, or TRK fusion protein, is constantly active, triggering a permanent signal cascade.
These proteins become the primary driver of the spread and growth of tumors in patients with TRK fusion cancer.
TRK fusion cancer is not limited to certain types of cells or tissues and can occur in any part of the body.
NTRK gene fusions occur in various adult and pediatric solid tumors with varying prevalence, including appendiceal cancer, breast cancer, cholangiocarcinoma, colorectal cancer, GIST, infantile fibrosarcoma, lung cancer, mammary analogue secretory carcinoma of the salivary gland, melanoma, pancreatic cancer, thyroid cancer, and various sarcomas.
Only sensitive and specific tests can reliably detect TRK fusion cancer.
Next-generation sequencing ( NGS ) can provide a comprehensive view of genomic alterations across a large number of genes.
Fluorescence in situ hybridization ( FISH ) can also be used to test for TRK fusion cancer, and immunohistochemistry ( IHC ) can be used to detect the presence of TRK protein. ( Xagena )
Source: Loxo Oncology, 2018