Blu 285 Side Effects

Blu 285 is a selective oral inhibitor that targets kit exon 17 and pdgfrα d842 activation loop mutants.

Blu 285 side effects.

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. Most adverse events were grade 1 or grade 2. The most common nonhematologic side effects of avapritinib were periorbital and peripheral edema fatigue nausea abdominal pain and diarrhea among others. Blu 285 appeared to be well tolerated at all doses.

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 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 appeared well tolerated. 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.

Avapritinib blu 285 binds the active conformation of the kinase and shows antitumor activity. The most common hematologic adverse effects were anemia thrombocytopenia and neutropenia. More than two patients experienced grade 3 treatment related neutropenia 13 anemia 7 and periorbital 7. 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.

Ayvakit can cause serious side effects including bleeding inside the skull effects on the central nervous system and harm to a newborn baby. Most adverse events were grade 1 or 2 but half of the patients experienced a grade 3 or 4 event. The majority of the aes were grade 1 or 2 and included fatigue dizziness headache rash shingles anemia and thrombocytopenia n 1 for each. 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.

Avapritinib blu 285 attenuates the transport function of both abcb1 and abcg2.