Entrectinib (1 brand name, 2 dosage forms, 1 route)
Available dosage forms: PELLETS, CAPSULE.
Routes of administration: ORAL.
Brand Names
- ROZLYTREK
Contraindications
None.
Adverse Reactions
The following clinically significant adverse reactions are described elsewhere in the labeling: Congestive Heart Failure [see Warnings and Precautions (5.1)] Central Nervous System Effects [see Warnings and Precautions (5.2)] Skeletal Fractures [see Warnings and Precautions (5.3)] Hepatotoxicity [see Warnings and Precautions (5.4)] Hyperuricemia [see Warnings and Precautions (5.5)] QT Interval Prolongation [see Warnings and Precautions (5.6)] Vision Disorders [see Warnings and Precautions (5.7)]
Mechanism of Action
Entrectinib is an inhibitor of the tropomyosin receptor tyrosine kinases (TRK) TRKA, TRKB, and TRKC (encoded by the neurotrophic tyrosine receptor kinase [NTRK] genes NTRK1, NTRK2, and NTRK3, respectively), proto-oncogene tyrosine-protein kinase ROS1 (ROS1), and anaplastic lymphoma kinase (ALK) with IC50 values of 0.1 to 2 nM. Entrectinib also inhibits JAK2 and TNK2 with IC50 values > 5 nM. The major active metabolite of entrectinib, M5, showed similar in vitro activity against TRK, ROS1, and ALK. Fusion proteins that include TRK, ROS1, or ALK kinase domains can drive tumorigenic potential through hyperactivation of downstream signaling pathways leading to unconstrained cell proliferation. Entrectinib demonstrated in vitro and in vivo inhibition of cancer cell lines derived from multiple tumor types harboring NTRK, ROS1, and ALK fusion genes. Entrectinib demonstrated steady-state brain-to-plasma concentration ratios of 0.4 – 2.2 in multiple animal species (mice, rats, and dogs) and demonstrated in vivo anti-tumor activity in mice with intracranial implantation of TRKA- and ALK-driven tumor cell lines.