Entrectinib: A New Selective Tyrosine Kinase Inhibitor Approved for the Treatment of Pediatric and Adult Patients with NTRK Fusionpositive, Recurrent or Advanced Solid Tumors

Curr Med Chem. 2022;29(15):2602-2616. doi: 10.2174/0929867328666210914121324.


Background: Entrectinib is a highly potent ATP-competitive and selective inhibitor of tyrosine kinases - Trk A B C, ALK, and ROS1. It was developed by Roche and initially approved in Japan in 2019 to treat pediatric and adult patients with NTRK fusionpositive, recurrent, or advanced solid tumors. In August 2019, entrectinib received accelerated approval by the U.S FDA for this indication. It is also the first FDA-approved drug designed to target both NTRK and ROS1.

Objective: We aim to summarize recent studies related to the synthesis, mechanism of action, and clinical trials of the newly approved selective tyrosine kinase inhibitor entrectinib.

Methods: We conduct a literature review of the research studies on the new highly-potent small-molecule entrectinib.

Conclusion: Entrectinib, based on three clinical studies (ALKA, STARTRK-1, and STARTRK-2), was well tolerated, with a manageable safety profile. It induced clinically meaningful responses in recurrent or advanced solid tumors associated with NTRK fusion- positive or ROS1+ NSCLC. It demonstrated substantial efficacy in patients with CNS metastases.

Keywords: ALK; Entrectinib; NTRK fusion-positive tumors; ROS1 inhibitor; Trk ABC; indazol benzamide.

Publication types

  • Review

MeSH terms

  • Adult
  • Benzamides
  • Child
  • Humans
  • Indazoles / pharmacology
  • Indazoles / therapeutic use
  • Lung Neoplasms* / drug therapy
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Protein-Tyrosine Kinases*
  • Proto-Oncogene Proteins
  • Receptor Protein-Tyrosine Kinases / genetics


  • Benzamides
  • Indazoles
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • Receptor Protein-Tyrosine Kinases
  • entrectinib