{"entity":{"id":"crown","kind":"trial","name":"CROWN","aka":[],"tldr":"The trial with the longest disease control ever seen for a targeted lung cancer pill: most patients still progression-free at five years.","summary":"296 patients. At 5 years, PFS was 60% with lorlatinib versus 8% with crizotinib (HR 0.19); median PFS not reached after >60 months of follow-up. Intracranial progression was nearly abolished (5-year cumulative incidence ~8% in patients without baseline brain metastases). Neurocognitive, mood, weight, and lipid effects require management.","status":"positive","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT03052608","url":"https://clinicaltrials.gov/study/NCT03052608"}],"tags":[],"related":[],"cancers":["nsclc","secondary-brain-tumours","alk-positive-nsclc"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["alk"],"drugs":["lorlatinib"],"companies":["pfizer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["ross-camidge","solomon-benjamin","ahn-myung-ju"],"bottlenecks":[],"keyPapers":["paper-shaw-crown-lorlatinib-crizotinib-nejm-2020","paper-crown-lancet-respir-med-2023-update"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03052608","phase":"3","setting":"First-line ALK-positive advanced NSCLC: lorlatinib vs crizotinib","sponsor":"Pfizer","result":"5-year PFS 60% vs 8%, HR 0.19 (JCO 2024).","started":"2017-04-27","startedType":"actual","yearReported":2020,"enrolled":296,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival at 5 years (BICR)","primary":true,"unit":"%","arms":[{"name":"Lorlatinib","n":149,"value":60},{"name":"Crizotinib","n":147,"value":8}],"hr":0.19,"ci":[0.13,0.27],"source":"https://ascopubs.org/doi/10.1200/JCO.24.00581"},{"endpoint":"Intracranial progression at 5 years","unit":"%","arms":[{"name":"Lorlatinib","value":8,"note":"Cumulative incidence in patients without baseline brain metastases"},{"name":"Crizotinib","value":40}],"source":"https://ascopubs.org/doi/10.1200/JCO.24.00581"}],"replication":"Single pivotal trial versus crizotinib; consistent with ALEX (alectinib) and eXalt3 (ensartinib) for the class, with lorlatinib showing the longest PFS."},"route":"/trials/crown/","neighbours":{"cancer":[{"id":"alk-positive-nsclc","kind":"cancer","name":"ALK-positive non-small-cell lung cancer","route":"/cancers/alk-positive-nsclc/"},{"id":"secondary-brain-tumours","kind":"cancer","name":"Brain metastases (secondary brain tumours)","route":"/cancers/secondary-brain-tumours/"},{"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/"}],"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/"}],"drug":[{"id":"lorlatinib","kind":"drug","name":"Lorlatinib","route":"/drugs/lorlatinib/"}],"company":[{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"}],"person":[{"id":"solomon-benjamin","kind":"person","name":"Benjamin Solomon","route":"/people/solomon-benjamin/"},{"id":"ross-camidge","kind":"person","name":"D. Ross Camidge","route":"/people/ross-camidge/"},{"id":"ahn-myung-ju","kind":"person","name":"Myung-Ju Ahn","route":"/people/ahn-myung-ju/"}],"paper":[{"id":"paper-crown-lancet-respir-med-2023-update","kind":"paper","name":"Efficacy and safety of first-line lorlatinib versus crizotinib in patients with advanced, ALK-positive non-small-cell lung cancer: updated analysis of data from the phase 3, randomised, open-label CROWN study","route":"/key-papers/paper-crown-lancet-respir-med-2023-update/"},{"id":"paper-shaw-crown-lorlatinib-crizotinib-nejm-2020","kind":"paper","name":"First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer","route":"/key-papers/paper-shaw-crown-lorlatinib-crizotinib-nejm-2020/"}],"pairing":[{"id":"targeted-before-io-nsclc","kind":"pairing","name":"Sequence: targeted therapy before immunotherapy in driver-positive NSCLC","route":"/pairings/targeted-before-io-nsclc/"}],"trial":[{"id":"nct01828099","kind":"trial","name":"ASCEND-4","route":"/trials/nct01828099/"},{"id":"nct02767804","kind":"trial","name":"eXalt3","route":"/trials/nct02767804/"},{"id":"profile-1014","kind":"trial","name":"PROFILE 1014","route":"/trials/profile-1014/"}]}}