{"entity":{"id":"brigatinib","kind":"drug","name":"Brigatinib","aka":[],"tldr":"Brigatinib is an ALK pill with strong brain activity, approved first after crizotinib and then first line after beating it in ALTA-1L.","summary":"Brigatinib is a second-generation ALK inhibitor with broad activity against resistance mutations including G1202R, and at higher doses it also inhibits wild-type EGFR; it penetrates the brain well. The ALTA trial (2017) established activity after crizotinib, and ALTA-1L (2018 to 2020) showed first-line superiority over crizotinib with median progression-free survival of 24 versus 11 months and a 78% intracranial response rate. It was approved in the US in 2017 after crizotinib and in 2020 first line, and in the EU in 2018. Early pulmonary events in the first week are its distinctive toxicity, which is why treatment starts with a 90 mg lead-in dose before escalation. It competes with alectinib and lorlatinib in the first line, and no trial has directly compared them. Brigatinib is an ALK pill whose main strengths are brain activity and coverage of resistance mutations.","status":"approved","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Brigatinib","links":[{"label":"ALTA (JCO 2017)","url":"https://doi.org/10.1200/JCO.2016.71.5904"},{"label":"ALTA-1L (NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1810171"},{"label":"Label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=brigatinib"},{"label":"NICE TA571: brigatinib for treating ALK-positive advanced non-small-cell lung cancer after crizotinib","url":"https://www.nice.org.uk/guidance/ta571"},{"label":"NICE TA670: brigatinib for ALK-positive advanced non-small-cell lung cancer not previously treated with an ALK inhibitor","url":"https://www.nice.org.uk/guidance/ta670"}],"tags":["gap-fill"],"related":["alk-fusion"],"cancers":["nsclc","alk-positive-nsclc","lung-cancer"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["alk"],"drugs":[],"companies":["takeda"],"institutions":[],"pathways":[],"terms":[],"trials":["alta","alta-1l"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Alunbrig","modality":"Small-molecule ALK/EGFR TKI (second generation)","mechanism":"Broad-spectrum ALK inhibitor with activity against G1202R and other resistance mutations plus wild-type EGFR at higher doses.","approvals":[{"region":"US","year":2017,"indication":"ALK-positive metastatic NSCLC after crizotinib"},{"region":"US","year":2020,"indication":"First-line ALK-positive metastatic NSCLC"},{"region":"EU","year":2018,"indication":"ALK-positive NSCLC"},{"region":"England (NICE)","year":2019,"indication":"ALK-positive advanced non-small-cell lung cancer after crizotinib","note":"TA571, published 20 March 2019, subject to the commercial arrangement."},{"region":"England (NICE)","year":2021,"indication":"ALK-positive advanced non-small-cell lung cancer not previously treated with an ALK inhibitor","note":"TA670, published 27 January 2021 (ALTA-1L), subject to the commercial arrangement."}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[{"date":"2017-04-28","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint, with a confirmatory trial required.","indication":"Patients with ALK-positive metastatic NSCLC that have progressed or are intolerant to crizotinib"},{"date":"2020-05-22","type":"conversion","region":"US","note":"Confirmed: the accelerated approval of 2017 converted to traditional approval 3.1 years after it was granted.","indication":"Patients with ALK-positive metastatic NSCLC that have progressed or are intolerant to crizotinib"}]},"route":"/drugs/brigatinib/","neighbours":{"biomarker":[{"id":"alk-fusion","kind":"biomarker","name":"ALK fusion (ALK-positive)","route":"/biomarkers/alk-fusion/"}],"cancer":[{"id":"alk-positive-nsclc","kind":"cancer","name":"ALK-positive non-small-cell lung cancer","route":"/cancers/alk-positive-nsclc/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"vestibular-schwannoma","kind":"cancer","name":"Vestibular schwannoma (acoustic neuroma)","route":"/cancers/vestibular-schwannoma/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"alk","kind":"target","name":"ALK","route":"/targets/alk/"}],"company":[{"id":"takeda","kind":"company","name":"Takeda","route":"/companies/takeda/"}],"trial":[{"id":"alta","kind":"trial","name":"ALTA","route":"/trials/alta/"},{"id":"alta-1l","kind":"trial","name":"ALTA-1L","route":"/trials/alta-1l/"},{"id":"intuitt-nf2","kind":"trial","name":"INTUITT-NF2","route":"/trials/intuitt-nf2/"},{"id":"nct06813079","kind":"trial","name":"Using Tumor Models to Determine Treatments","route":"/trials/nct06813079/"}],"paper":[{"id":"paper-alta-jco-2017","kind":"paper","name":"Brigatinib in patients with crizotinib-refractory ALK-positive non-small-cell lung cancer: a randomized, multicenter phase II trial (ALTA)","route":"/key-papers/paper-alta-jco-2017/"},{"id":"paper-intuitt-nf2-brigatinib-plotkin-nejm-2024","kind":"paper","name":"INTUITT-NF2: brigatinib in NF2-related schwannomatosis with progressive tumours","route":"/key-papers/paper-intuitt-nf2-brigatinib-plotkin-nejm-2024/"},{"id":"paper-gainor-alk-resistance-mutations-cancer-discov-2016","kind":"paper","name":"Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer","route":"/key-papers/paper-gainor-alk-resistance-mutations-cancer-discov-2016/"}],"term":[{"id":"lung-uk-drug-access","kind":"term","name":"Lung cancer drugs in England: what NICE has recommended","route":"/terms/lung-uk-drug-access/"}],"pathway":[{"id":"nsclc-signalling","kind":"pathway","name":"Non-small cell lung cancer (KEGG map)","route":"/pathways/nsclc-signalling/"}]}}