{"entity":{"id":"navigator","kind":"trial","name":"NAVIGATOR","aka":[],"tldr":"NAVIGATOR showed that avapritinib shrank almost every GIST driven by the PDGFRA D842V mutation, a type that had resisted every earlier drug, and won the drug its approval for that group.","summary":"NAVIGATOR was the first-in-human phase 1 study of avapritinib, a kinase inhibitor designed to bind the active conformation of KIT and PDGFRA and so to inhibit the D842V mutation that imatinib, sunitinib and regorafenib cannot. It enrolled patients with unresectable gastrointestinal stromal tumour in dose-escalation and expansion cohorts, including a cohort with PDGFRA D842V mutations and cohorts of KIT-mutant disease after prior kinase inhibitors.\n\nIn PDGFRA D842V-mutant GIST the response rate was very high and responses lasted for years, a transformation for a group with essentially no prior effective therapy, and avapritinib was approved in the United States in January 2020 for that indication. Activity in later-line KIT-mutant disease was more modest, and the confirmatory VOYAGER trial did not show superiority over regorafenib in that setting. Cognitive side effects and intracranial haemorrhage at higher doses were the notable toxicities.","status":"positive","asOf":"2026-09-17","links":[{"label":"ClinicalTrials.gov NCT02508532","url":"https://clinicaltrials.gov/study/NCT02508532"}],"tags":["subtype-trials"],"related":[],"cancers":["gist-pdgfra-d842v","gist","sarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":["avapritinib"],"companies":["blueprint-medicines"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["michael-heinrich"],"bottlenecks":[],"keyPapers":["paper-navigator-avapritinib-heinrich-lancet-oncol-2020"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02508532","phase":"1","setting":"Unresectable or metastatic gastrointestinal stromal tumour, including PDGFRA D842V-mutant disease and imatinib-resistant KIT-mutant disease: avapritinib dose escalation and expansion","sponsor":"Blueprint Medicines","result":"Very high, durable response rate in PDGFRA D842V-mutant GIST; approved for that indication in January 2020.","yearReported":2020,"enrolled":250,"outcomes":[{"endpoint":"Overall response, PDGFRA D842V-mutant GIST (dose-expansion primary endpoint)","primary":true,"unit":"%","arms":[{"name":"Avapritinib","n":56,"value":88,"note":"95% CI 76 to 95; median follow-up 15.9 months"}],"source":"https://doi.org/10.1016/S1470-2045(20)30269-2"},{"endpoint":"Complete response, PDGFRA D842V-mutant GIST","unit":"%","arms":[{"name":"Avapritinib","n":56,"value":9}],"source":"https://doi.org/10.1016/S1470-2045(20)30269-2"},{"endpoint":"Treatment-related grade 3-4 adverse events","unit":"%","arms":[{"name":"Avapritinib","n":82,"value":57,"note":"Most common anaemia (17%); no treatment-related deaths"}],"source":"https://doi.org/10.1016/S1470-2045(20)30269-2"}]},"route":"/trials/navigator/","neighbours":{"cancer":[{"id":"gist","kind":"cancer","name":"Gastrointestinal stromal tumour (GIST)","route":"/cancers/gist/"},{"id":"gist-pdgfra-d842v","kind":"cancer","name":"PDGFRA D842V-mutant GIST","route":"/cancers/gist-pdgfra-d842v/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"}],"drug":[{"id":"avapritinib","kind":"drug","name":"Avapritinib","route":"/drugs/avapritinib/"}],"company":[{"id":"blueprint-medicines","kind":"company","name":"Blueprint Medicines","route":"/companies/blueprint-medicines/"}],"person":[{"id":"michael-heinrich","kind":"person","name":"Michael C. Heinrich","route":"/people/michael-heinrich/"}],"paper":[{"id":"paper-navigator-avapritinib-heinrich-lancet-oncol-2020","kind":"paper","name":"NAVIGATOR: avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour","route":"/key-papers/paper-navigator-avapritinib-heinrich-lancet-oncol-2020/"}]}}