Pralsetinib (1 brand name, 1 dosage form, 1 route)
Available dosage forms: CAPSULE.
Routes of administration: ORAL.
Brand Names
- GAVRETO
Boxed Warning
GAVRETO may increase the risk for serious infections, including bacterial, fungal, viral and opportunistic infections, which can lead to hospitalization or death. Withhold, reduce the dose or permanently discontinue GAVRETO based on severity [see Dosage and Administration (2.3), Warnings and Precautions (5.1)].
Contraindications
None.
Adverse Reactions
The following clinically significant adverse reactions are described elsewhere in the labeling: Serious Infections, Including Opportunistic Infections [see Warnings and Precautions (5.1)] Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions (5.2)] Hypertension [see Warnings and Precautions (5.3)] Hepatotoxicity [see Warnings and Precautions (5.4)] Hemorrhagic Events [see Warnings and Precautions (5.5)] Tumor Lysis Syndrome [see Warnings and Precautions (5.6)] Risk of Impaired Wound Healing [see Warnings and Precautions (5.7)] Embryo-Fetal Toxicity [see Warnings and Precautions (5.8)]
Mechanism of Action
Pralsetinib is a kinase inhibitor of wild-type RET and oncogenic RET fusions (CCDC6-RET) and mutations (RET V804L, RET V804M and RET M918T) with half maximal inhibitory concentrations (IC50s) less than 0.5 nM. In purified enzyme assays, pralsetinib inhibited DDR1, TRKC, FLT3, JAK1-2, TRKA, VEGFR2, PDGFRB, and FGFR1 at higher concentrations that were still clinically achievable at Cmax. In cellular assays, pralsetinib inhibited RET at approximately 14-, 40-, and 12-fold lower concentrations than VEGFR2, FGFR2, and JAK2, respectively. Certain RET fusion proteins and activating point mutations can drive tumorigenic potential through hyperactivation of downstream signaling pathways leading to uncontrolled cell proliferation. Pralsetinib exhibited anti-tumor activity in cultured cells and animal tumor implantation models harboring oncogenic RET fusions or mutations including KIF5B-RET, CCDC6-RET, RET M918T, RET C634W, RET V804E, RET V804L and RET V804M. In addition, pralsetinib prolonged survival in mice implanted intracranially with tumor models expressing KIF5B-RET or CCDC6-RET.