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Synonyms: Ayvakit® | Ayvakyt® | BLU-285 | BLU285
avapritinib is an approved drug (FDA & EMA (2020))
Compound class: Synthetic organic
Comment: Avapritinib (BLU-285) was developed by Blueprint Medicines as an oral precision therapy to selectively and potently inhibit KIT and PDGFRA mutant kinases . It is a Type I kinase inhibitor that binds the active kinase conformation. Avapritinib binds to the 'switch pocket' of KIT, a domain that regulates the enzyme's catalytic conformation. Compounds that act in this way are often referred to as switch control inhibitors . Another such switch control inhibitor is ripretinib.
Ligand Activity Visualisation Charts
These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.✖
|No information available.|
|Summary of Clinical Use|
|In early clinical evaluation avapritinib (BLU-285) demonstrated significant activity in patients with diseases associated with KIT (aggressive systemic mastocytosis (SM)  and gastrointestinal stromal tumour (GIST) ) and PDGFRA (GIST) activation loop mutations [3,5]. Avapritinib progressed to more advanced clinical evaluation for these indications. Click here to link to ClinicalTrials.gov's full list of avapritinib trials. The developer submitted two New Drug Applications (NDAs) for avapritinib to the FDA; the first for PDGFRA exon 18 mutant GIST (irrespective of prior therapy) and the second as fourth-line therapy for GIST. NDAs for second-line and third-line treatment of GIST will be determined by results from ongoing clinical trials.
Prior to full approval both the EMA and FDA had granted avapritinib orphan designation for the treatment of GIST and mastocytosis. The FDA granted Breakthrough Therapy Designation to avapritinib for two specific forms of these conditions: unresectable or metastatic GIST harbouring the PDGFRA D842V mutation and advanced SM (including aggressive SM and SM with an associated haematologic neoplasm and mast cell leukemia). The first full FDA approval was granted in January 2020, for use in genomically defined unresectable or metastatic PDGFRA exon 18 mutant GIST . Results from NCT03465722, looking at avapritinib vs. regorafenib in heavily pretreated KIT and PDGFRA wild type cancers, indicate non-superiority compared to regorafenib. EMA approval for this indication followed in September 2020.
In June 2021 the FDA approved avapritinib for advanced systemic mastocytosis (AdvSM; including aggressive systemic mastocytosis), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL), based on results from the EXPLORER (NCT02561988) and PATHFINDER (NCT03580655) trials.
|Clinical Trial ID||Title||Type||Source||Comment||References|
|NCT03580655||(PATHFINDER) Study to Evaluate Efficacy and Safety of Avapritinib (BLU-285), A Selective KIT Mutation-targeted Tyrosine Kinase Inhibitor, in Patients With Advanced Systemic Mastocytosis||Phase 2 Interventional||Blueprint Medicines Corporation||PATHFINDER trial|
|NCT02561988||(EXPLORER) Study of BLU-285 in Patients With Advanced Systemic Mastocytosis (AdvSM) and Relapsed or Refractory Myeloid Malignancies||Phase 1 Interventional||Blueprint Medicines Corporation||EXPLORER trial|