Avapritinib (1 brand name, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- AYVAKIT
Contraindications
None.
Adverse Reactions
The following clinically significant adverse reactions are described elsewhere in the labeling: Intracranial hemorrhage [see Warnings and Precautions (5.1)] Cognitive effects [see Warnings and Precautions (5.2)] Photosensitivity [see Warnings and Precautions (5.3)]
Mechanism of Action
Avapritinib is a tyrosine kinase inhibitor that targets KIT D816V, PDGFRA and PDGFRA D842 mutants as well as multiple KIT exon 11, 11/17 and 17 mutants with half maximal inhibitory concentrations (IC50s) less than 25 nM in biochemical assays. Certain mutations in PDGFRA and KIT can result in the autophosphorylation and constitutive activation of these receptors which can contribute to tumor and mast cell proliferation. Other potential targets for avapritinib include wild type KIT, PDGFRB, and CSFR1. In cellular assays, avapritinib inhibited the autophosphorylation of KIT D816V with an IC50 of 4 nM, approximately 48-fold lower concentration than wild-type KIT. In cellular assays, avapritinib inhibited the proliferation in KIT mutant cell lines, including a murine mastocytoma cell line and a human mast cell leukemia cell line. Avapritinib also showed growth inhibitory activity in a xenograft model of murine mastocytoma with KIT exon 17 mutation. Avapritinib inhibited the autophosphorylation of PDGFRA D842V, a mutation associated with resistance to approved kinase inhibitors, with an IC50 of 30 nM. Avapritinib also had anti-tumor activity in mice implanted with an imatinib-resistant patient-derived xenograft model of human GIST with activating KIT exon 11/17 mutations.