Avapritinib (Ayvakit)

General information

Class/mechanism from the NCI Drug Dictionary: An orally bioavailable inhibitor of specific mutated forms of platelet-derived growth factor receptor alpha (PDGFR alpha; PDGFRa) and mast/stem cell factor receptor c-Kit (SCFR), with potential antineoplastic activity. Upon oral administration, avapritinib specifically binds to and inhibits specific mutant forms of PDGFRa and c-Kit, including the PDGFRa D842V mutant and various KIT exon 17 mutants. This results in the inhibition of PDGFRa- and c-Kit-mediated signal transduction pathways and the inhibition of proliferation in tumor cells that express these PDGFRa and c-Kit mutants.
Route: PO
Extravasation: n/a

• IUPHAR/BPS

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.

Diseases for which it is established (work in progress)

• Gastrointestinal stromal tumor
• Systemic mastocytosis

Patient Drug Information

• Avapritinib (Ayvakit) Package Insert

History of changes in FDA indication

• 2020-01-09: Initial approval for adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including D842V mutations. (Based on NAVIGATOR)
• 2021-06-16: Approved for adult patients with advanced systemic mastocytosis (AdvSM), including patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL). (Based on EXPLORER and PATHFINDER)
• 2023-05-22: Approved for the treatment of adults with indolent systemic mastocytosis. (Based on PIONEER)

History of changes in EMA indication

• 2020-09-24: Initial conditional authorization as Ayvakyt. Ayvakyt is indicated as monotherapy for the treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumours (GIST) harbouring the platelet-derived growth factor receptor alpha (PDGFRA) D842V mutation. (Based on NAVIGATOR)
• 2022-03-24: Ayvakyt is indicated as monotherapy for the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated haematological neoplasm (SM-AHN) or mast cell leukaemia (MCL), after at least one systemic therapy. (Based on EXPLORER and PATHFINDER)
• 2023-11-09: CHMP recommendation - Ayvakyt is indicated for the treatment of adult patients with indolent systemic mastocytosis (ISM) with moderate to severe symptoms inadequately controlled on symptomatic treatment.

Also known as

• Code name: BLU-285
• Brand name: Ayvakit, Ayvakyt