Characteristics
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 2020, entrectinib received conditional marketing authorization in Europe, as monotherapy for the treatment of adult and paediatric patients 12 years of age and older with solid tumours expressing a NTRK gene fusion who, a) have a disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity, b) have not received a prior NTRK inhibitor, and c) have no satisfactory treatment options [4].
Entrectinib has received accelerated approval by the FDA for adult and pediatric patients 12 years of age and older with solid tumors that a) have a NTRK gene fusion without a known acquired resistance mutation and b) are metastatic or where surgical resection is likely to result in severe morbidity, and c) have progressed following treatment or have no satisfactory alternative therapy [5].
References
- 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.
- 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.
- 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.
ROZLYTREK (entrectinib), EMA Summary of medicinal Product Characteristics. 2022.
- ROZLYTREK (entrectinib), USA Prescribing Information. 2022.