Entrectinib (Rozlytrek)

General information

Class/mechanism, from the NCI Drug Dictionary: An orally bioavailable inhibitor of the tyrosine kinases tropomyosin receptor kinases (Trk) A, B and C, C-ros oncogene 1 (ROS1) and anaplastic lymphoma kinase (ALK), with potential antineoplastic activity. Upon administration, entrectinib binds to and inhibits TrkA, TrkB, TrkC, ROS1 and ALK. Inhibition of these kinases may result in a disruption of TrkA-, TrkB-, TrkC-, ROS1-, and ALK-mediated signaling. This leads to an induction of apoptosis and an inhibition of tumor cell proliferation in tumor cells that express these kinases.
Route: PO
Extravasation: n/a

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias or the prescribing information.

Diseases for which it is established

• ROS1+ NSCLC
• Solid malignancies with NTRK fusions

History of changes in FDA indication

• 2019-08-15: Granted accelerated approval for adults and pediatric patients 12 years of age and older with solid tumors that have a neurotrophic tyrosine receptor kinase (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. (Based on ALKA-372-001, STARTRK-1, and STARTRK-2)
• 2019-08-15: Approved for adults with metastatic non-small cell lung cancer (NSCLC) whose tumors are ROS1-positive. (Based on ALKA-372-001, STARTRK-1, and STARTRK-2)
• 2023-10-20: Granted accelerated approval for pediatric patients older than 1 month with solid tumors that have a neurotrophic tyrosine receptor kinase (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. (Based on STARTRK-NG & TAPISTRY)

History of changes in EMA indication

• 2020-07-31: Initial conditional authorization as Rozlytrek. Rozlytrek as monotherapy is indicated for the treatment of adult and paediatric patients 12 years of age and older, with solid tumours expressing a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, who have a disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity, and who have not received a prior NTRK inhibitor and who have no satisfactory treatment options.
• 2020-07-31: Rozlytrek as monotherapy is indicated for the treatment of adult patients with ROS1-positive, advanced non-small cell lung cancer (NSCLC) not previously treated with ROS1 inhibitors.

History of changes in Health Canada indication

• 2020-02-10: Initial notice of compliance with conditions for the treatment of adult patients with unresectable locally advanced or metastatic extracranial solid tumours, including brain metastases, that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, and with no satisfactory treatment options.

History of changes in PMDA indication

• 2019-06-18: Newly indicated for the treatment of NTRK fusion gene positive advanced or recurrent solid tumours.
• 2020-02-21: New indication and a new dosage for the treatment of ROS1 fusion gene-positive unresectable advanced or recurrent non-small cell lung cancer.

Patient Drug Information

• Entrectinib (Rozlytrek) Package Insert

Also known as

• Code name: RXDX-101
• Brand name: Rozlytrek