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Entrectinib (RDX-101, NMS-P626), a first-generation TRK inhibitor, is a small molecule multi-kinase inhibitor [1-3]. Entrectinib is orally available, with a plasma half-life of 20–22 hours, allowing for a once daily, continuous dosing regimen (600 mg daily was identified as the maximum tolerated dose in adults in phase 1/2 trials [3]).

In 2017, entrectinib was granted breakthrough therapy and orphan drug designation by the US FDA [4]. In addition, the EMA granted entrectinib a priority medicines designation in the same year [5].  In June 2019, entrectinib was approved in Japan for the treatment of adult and paediatric patients NTRK fusion-positive, advanced recurrent solid tumours [6]. In August 2019, entrectinib was approved for the treatment of adults and pediatric patients ≥12 years of age and older with solid tumours that have a NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory standard therapy [7].


  1. Ardini E, Menichincheri M, Banfi P et al. Entrectinib, a Pan-TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications. Mol Cancer Ther 2016; 15: 628-639.
  2. Liu D, Offin M, Harnicar S et al. Entrectinib: an orally available, selective tyrosine kinase inhibitor for the treatment of NTRK, ROS1, and ALK fusion-positive solid tumors. Ther Clin Risk Manag 2018; 14: 1247-1252.
  3. Drilon A, Siena S, Ou SI et al. Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1). Cancer Discov 2017; 7: 400-409.
  4. Drugs.com. Entrectinib Approval Status. 2019.
  5. eCancer News. EMA issues PRIME designation for entrectinib in NTRK fusion solid tumours. 2017.
  6. Roche. Media release. 2019. https://www.roche.com/media/releases/med-cor-2019-06-18.htm (accessed 24 June 2019).
  7. Food & Drug Administration. 2019. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-entrectinib-ntrk-solid-tumors-and-ros-1-nsclc (accessed 20 August 2019).