{"entity":{"id":"paper-explorer-avapritinib-advanced-systemic-mastocytosis-nat-med-2021","kind":"paper","name":"EXPLORER: safety and efficacy of avapritinib in advanced systemic mastocytosis (phase 1)","aka":[],"tldr":"The first study of avapritinib, a drug designed to hit the KIT D816V mutation that drives most mastocytosis, produced responses in three quarters of patients with advanced disease and set the dose for later trials.","summary":"Phase 1 dose-escalation and expansion study of 86 patients with advanced systemic mastocytosis treated with avapritinib, a selective inhibitor of KIT D816V.\n\nThe overall response rate in response-evaluable patients was 75 percent with deep and durable responses, falls in serum tryptase and KIT D816V allele burden, and a recommended dose of 200 mg daily; cognitive effects and intracranial bleeding (mainly with severe thrombocytopenia) were the notable toxicities. The results, with PATHFINDER, led to approval of avapritinib for advanced systemic mastocytosis in 2021.","asOf":"2026-09-18","links":[{"label":"Nat Med 2021","url":"https://doi.org/10.1038/s41591-021-01538-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34873347/"}],"tags":[],"related":[],"cancers":["advanced-systemic-mastocytosis"],"sections":[],"technologies":[],"targets":[],"drugs":["avapritinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2021,"doi":"10.1038/s41591-021-01538-9","pmid":"34873347","authors":"DeAngelo DJ, Radia DH, George TI, et al.","paperType":"observational","findings":["Overall response 75 percent in evaluable patients; complete remissions with full or partial haematological recovery in a substantial minority.","Intracranial haemorrhage occurred mainly in patients with platelet counts below 50,000 per microlitre, prompting a platelet threshold for treatment."],"whatItMeans":"Avapritinib is the most active drug in advanced systemic mastocytosis; platelet counts must be checked before and during treatment.","caveats":["Phase 1 without a comparator; response criteria changed between cohorts.","Cognitive adverse effects are common and dose-related."],"changedPractice":true,"participants":86},"route":"/key-papers/paper-explorer-avapritinib-advanced-systemic-mastocytosis-nat-med-2021/","neighbours":{"cancer":[{"id":"advanced-systemic-mastocytosis","kind":"cancer","name":"Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia)","route":"/cancers/advanced-systemic-mastocytosis/"}],"drug":[{"id":"avapritinib","kind":"drug","name":"Avapritinib","route":"/drugs/avapritinib/"}],"journal":[{"id":"nature-medicine","kind":"journal","name":"Nature Medicine","route":"/journals/nature-medicine/"}]}}