Selpercatinib (1 brand name, 2 dosage forms, 1 route)
Available dosage forms: TABLET, CAPSULE.
Routes of administration: ORAL.
Brand Names
- RETEVMO
Contraindications
None.
Adverse Reactions
The following clinically significant adverse reactions are described elsewhere in the labeling: Hepatotoxicity [see Warnings and Precautions (5.1)] Interstitial Lung Disease / Pneumonitis [see Warnings and Precautions (5.2)] Hypertension [see Warnings and Precautions (5.3)] QT Interval Prolongation [see Warnings and Precautions (5.4)] Hemorrhagic Events [see Warnings and Precautions (5.5)] Hypersensitivity [see Warnings and Precautions (5.6)] Tumor Lysis Syndrome [see Warnings and Precautions (5.7)] Risk of Impaired Wound Healing [see Warnings and Precautions (5.8)] Hypothyroidism [see Warnings and Precautions (5.9)] Slipped Capital Femoral Epiphysis/Slipped Upper Femoral Epiphysis in Adolescent Patients [see Warnings and Precautions (5.11)]
Mechanism of Action
Selpercatinib is a kinase inhibitor. Selpercatinib inhibited wild-type RET and multiple mutated RET isoforms as well as VEGFR1 and VEGFR3 with IC50 values ranging from 0.92 nM to 67.8 nM. In other enzyme assays, selpercatinib also inhibited FGFR 1, 2, and 3 at higher concentrations that were still clinically achievable. In cellular assays, selpercatinib inhibited RET at approximately 60-fold lower concentrations than FGFR1 and 2 and approximately 8-fold lower concentration than VEGFR3. Certain point mutations in RET or chromosomal rearrangements involving in-frame fusions of RET with various partners can result in constitutively activated chimeric RET fusion proteins that can act as oncogenic drivers by promoting cell proliferation of tumor cell lines. In in vitro and in vivo tumor models, selpercatinib demonstrated anti-tumor activity in cells harboring constitutive activation of RET proteins resulting from gene fusions and mutations, including CCDC6-RET, KIF5B-RET, RET V804M, and RET M918T. In addition, selpercatinib showed anti-tumor activity in mice intracranially implanted with a patient-derived RET fusion positive tumor.