Avapritinib blu 285 binds the active conformation of the kinase and shows antitumor activity.
Blu 285 side effects.
Blu 285 appeared to be well tolerated at all doses.
Avapritinib blu 285 attenuates the transport function of both abcb1 and abcg2.
The most common nonhematologic side effects of avapritinib were periorbital and peripheral edema fatigue nausea abdominal pain and diarrhea among others.
The majority of the aes were grade 1 or 2 and included fatigue dizziness headache rash shingles anemia and thrombocytopenia n 1 for each.
The most common hematologic adverse effects were anemia thrombocytopenia and neutropenia.
Results of a phase 1 study systemic mastocytosis sm encompasses a spectrum of mast cell disorders characterized by an accumulation of neoplastic mast cells in tissues visceral organs1 2.
No patients discontinued treatment due to adverse events aes and no grade 4 aes were reported.
This is a phase 1 open label first in human fih study designed to evaluate the safety tolerability pharmacokinetics pk pharmacodynamics pd and antineoplastic activity of avapritinib formerly blu 285 administered orally po in adult patients with unresectable gist or other relapsed or refractory solid tumors.
Avapritinib blu 285 a selective kit inhibitor is associated with high response rate and tolerable safety profile in advanced systemic mastocytosis.
Most adverse events were grade 1 or grade 2.
Blu 285 appeared well tolerated.
These mutations have not responded to other approved tyrosine kinase inhibitors.
Avapritinib blu 285 is a highly potent selective and orally active kit and pdgfra activation loop mutant kinases inhibitor with ic50s of 0 27 and 0 24 nm for kit d816v and pdgfra d842v respectively.
Blu 285 is a selective oral inhibitor that targets kit exon 17 and pdgfrα d842 activation loop mutants.
Avapritinib brand name ayvakit formerly blu 285 was approved january 9 2020 by the fda for gastrointestinal stromal tumors with a mutation in exon 18 of the platelet derived growth factor receptor alpha pdgfra including the d842v mutation.
Cellular assays measuring inhibition of kit mutant autophosphorylation confirm the activity of blu 285 against the kit d816 mutants d816v hmc1 2 cells ic50 3 nm and d816y p815 cells ic50 22 nm as well as other kit exon 17 mutants such as n822k kasumi cells ic50 40 nm.
Adverse events common side effects for patients taking avapritinib were edema swelling nausea fatigue asthenia abnormal physical weakness or lack of energy cognitive impairment vomiting decreased appetite diarrhea hair color changes increased lacrimation secretion of tears abdominal pain constipation rash and dizziness.
