A selective tyrosine kinase inhibitor with specificity, at low nanomolar concentrations, for all of three Trk proteins (encoded by the NTRK1, 2, and 3 genes, respectively) as well as the ROS1, and ALK receptor tyrosine kinases.
Entrectinib has potential antitumor activity.
Entrectinib is a selective pan-trk receptor tyrosine kinase inhibitor (TKI) targeting gene fusions in trkA, trkB, and trkC.
Trade name Rozlytrek.
An anti-cancer drug used to treat ROS1-positive non-small cell lung cancer and NTRK fusion-positive solid tumors.
A selective tyrosine kinase inhibitor (TKI), of the tropomyosin receptor kinases (Trk) A, B and C, C-ros oncogene 1 (ROS1) and anaplastic lymphoma kinase (ALK).
Routes of administration by mouth.
Approved to treat adults and adolescents whose cancers have a specific genetic feature, abnormal NTRK genes.
It is not approved for use in those less than 12 years of age.
Common side effects include: fatigue, constipation, dysgeusia, edema, dizziness, diarrhea, nausea, dysesthesia, dyspnea, myalgia, cognitive impairment, weight gain, cough, vomiting, fever, arthralgia and vision disorders.
More serious side effects of are congestive heart failure, central nervous system effects, skeletal fractures, hepatotoxicity, hyperuricemia, QT prolongation and vision disorders.
Has orphan drug designation and rare pediatric disease designation for the treatment of neuroblastoma and orphan drug designation for treatment of TrkA-, TrkB-, TrkC-, ROS1- and ALK-positive non-small cell lung cancer (NSCLC) and metastatic colorectal cancer (mCRC).
It is approved treatment designed to target both ROS1 and NTRK that also shows response in cancer that has spread to the brain.
Some kinases undergo rearrangement in human cancers include the anaplastic lymphoma kinase (ALK), ROS1 kinase, and the neurotrophic receptor tyrosine kinases (NTRKs).
The drug is orally administered, once daily.
As a ROS1 inhibitor, entrectinib has demonstrated in cellular anti-proliferative studies to have a 36-fold greater potency against ROS1 as compared with the ROS1 inhibitor, crizotinib.
Entrectinib has also demonstrated in-vitro efficacy against potential Trk inhibitor resistance mutations such as NTRK1 F589L, NTRK1 V573M, NTRK1 G667S.