{"entity":{"id":"explorer","kind":"trial","name":"EXPLORER","aka":["BLU-285-2101"],"tldr":"EXPLORER was the first human study of avapritinib, a pill designed to block the KIT D816V mutation that drives almost every case of advanced systemic mastocytosis; three quarters of evaluable patients responded and a third went into complete remission, and the drug was approved for the disease in 2021.","summary":"EXPLORER was a phase 1 dose-escalation and expansion study of avapritinib (BLU-285), a selective inhibitor of KIT D816V, in 86 patients with advanced systemic mastocytosis or relapsed myeloid malignancies, 69 of whom had centrally confirmed advanced systemic mastocytosis. The primary endpoints were the maximum tolerated dose, the recommended phase 2 dose and safety; response rate and measures of mast cell burden were secondary.\n\nThe maximum tolerated dose was not reached and 200 mg and 300 mg daily were studied in expansion. Among 53 response-evaluable patients the overall response rate was 75 percent with a complete remission rate of 36 percent, and avapritinib halved marrow mast cells and serum tryptase in almost every patient. Periorbital oedema, anaemia, diarrhoea and thrombocytopenia were the common adverse events; intracranial bleeding occurred in 13 percent overall but in 1 percent of patients without severe thrombocytopenia, which is why the label requires a platelet count of 50 x 10^9/L or more. Together with the phase 2 PATHFINDER trial it supported approval of avapritinib for advanced systemic mastocytosis in the United States in June 2021.","status":"positive","asOf":"2026-09-22","links":[{"label":"ClinicalTrials.gov NCT02561988","url":"https://clinicaltrials.gov/study/NCT02561988"}],"tags":["soc-trials"],"related":[],"cancers":["advanced-systemic-mastocytosis","systemic-mastocytosis"],"sections":[],"technologies":["kinase-inhibitors"],"targets":[],"drugs":["avapritinib"],"companies":["blueprint-medicines"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-explorer-avapritinib-advanced-systemic-mastocytosis-nat-med-2021"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02561988","phase":"1","setting":"Advanced systemic mastocytosis (aggressive systemic mastocytosis, mastocytosis with an associated haematological neoplasm, mast cell leukaemia) and relapsed myeloid malignancies: first-in-human dose escalation and expansion of the selective KIT D816V inhibitor avapritinib at 30 to 400 mg daily","sponsor":"Blueprint Medicines Corporation","result":"Overall response rate 75 percent and complete remission rate 36 percent in 53 evaluable patients with advanced systemic mastocytosis; maximum tolerated dose not reached; recommended dose 200 mg daily; approved June 2021.","yearReported":2021,"enrolled":86,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall response rate (response-evaluable advanced systemic mastocytosis)","unit":"%","arms":[{"name":"Avapritinib 30 to 400 mg daily","n":53,"value":75}],"source":"https://doi.org/10.1038/s41591-021-01538-9"},{"endpoint":"Complete remission rate (response-evaluable advanced systemic mastocytosis)","unit":"%","arms":[{"name":"Avapritinib 30 to 400 mg daily","n":53,"value":36}],"source":"https://doi.org/10.1038/s41591-021-01538-9"},{"endpoint":"Reduction of 50% or more in serum tryptase","unit":"%","arms":[{"name":"Avapritinib 30 to 400 mg daily","value":99}],"source":"https://doi.org/10.1038/s41591-021-01538-9"},{"endpoint":"Intracranial bleeding","unit":"%","arms":[{"name":"Avapritinib, all patients","n":86,"value":13},{"name":"Avapritinib, patients without severe thrombocytopenia","value":1}],"source":"https://doi.org/10.1038/s41591-021-01538-9"},{"endpoint":"Periorbital oedema (any grade)","unit":"%","arms":[{"name":"Avapritinib 30 to 400 mg daily","n":86,"value":69}],"source":"https://doi.org/10.1038/s41591-021-01538-9"}]},"route":"/trials/explorer/","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/"},{"id":"systemic-mastocytosis","kind":"cancer","name":"Systemic mastocytosis","route":"/cancers/systemic-mastocytosis/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"drug":[{"id":"avapritinib","kind":"drug","name":"Avapritinib","route":"/drugs/avapritinib/"}],"company":[{"id":"blueprint-medicines","kind":"company","name":"Blueprint Medicines","route":"/companies/blueprint-medicines/"}],"paper":[{"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)","route":"/key-papers/paper-explorer-avapritinib-advanced-systemic-mastocytosis-nat-med-2021/"}]}}