{"entity":{"id":"alpine","kind":"trial","name":"ALPINE","aka":[],"tldr":"The first head-to-head trial in which a newer BTK inhibitor was both safer and more effective than ibrutinib.","summary":"ALPINE, trial NCT03734016 sponsored by BeOne, formerly BeiGene, and published in the New England Journal of Medicine in 2023, was the first head-to-head trial in which a newer BTK inhibitor was both safer and more effective than ibrutinib in relapsed or refractory chronic lymphocytic leukaemia. It randomised 652 patients to zanubrutinib or ibrutinib, met its primary progression-free survival endpoint including in del(17p) and TP53 disease, produced a higher response rate, less than half the rate of atrial fibrillation and fewer discontinuations, and the three-year update maintained the advantage. OnCo links it to chronic lymphocytic leukaemia, BTK as a target, zanubrutinib, ibrutinib, John Oyler, Jennifer R. Brown and the caution pairing about ibrutinib in patients with cardiac risk. Whether that superiority reflects the drug or the trial is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03734016","url":"https://clinicaltrials.gov/study/NCT03734016"}],"tags":[],"related":[],"cancers":["cll","cll-relapsed"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["btk"],"drugs":["zanubrutinib","ibrutinib"],"companies":["beone"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["oyler-john","jennifer-brown"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03734016","phase":"3","setting":"Relapsed or refractory CLL/SLL: zanubrutinib vs ibrutinib","sponsor":"BeOne (BeiGene)","result":"PFS HR 0.65; AF 5.2% vs 13.3%.","started":"2018-11-01","startedType":"actual","yearReported":2022,"enrolled":652,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival","primary":true,"arms":[{"name":"Zanubrutinib","n":327},{"name":"Ibrutinib","n":325}],"hr":0.65,"ci":[0.49,0.86],"p":"0.002","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2211582"},{"endpoint":"Overall response rate","unit":"%","arms":[{"name":"Zanubrutinib","value":86.2},{"name":"Ibrutinib","value":75.7}],"source":"https://doi.org/10.1056/NEJMoa2211582"},{"endpoint":"Atrial fibrillation/flutter","unit":"%","arms":[{"name":"Zanubrutinib","value":5.2},{"name":"Ibrutinib","value":13.3}],"source":"https://doi.org/10.1056/NEJMoa2211582"}],"replication":"ELEVATE-RR (acalabrutinib vs ibrutinib) showed non-inferior PFS with less atrial fibrillation; ALPINE is the only trial to show PFS superiority."},"route":"/trials/alpine/","neighbours":{"cancer":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"cll-relapsed","kind":"cancer","name":"Relapsed or refractory chronic lymphocytic leukaemia","route":"/cancers/cll-relapsed/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"btk","kind":"target","name":"BTK (Bruton tyrosine kinase)","route":"/targets/btk/"}],"drug":[{"id":"ibrutinib","kind":"drug","name":"Ibrutinib","route":"/drugs/ibrutinib/"},{"id":"zanubrutinib","kind":"drug","name":"Zanubrutinib","route":"/drugs/zanubrutinib/"}],"company":[{"id":"beone","kind":"company","name":"BeOne Medicines (formerly BeiGene)","route":"/companies/beone/"}],"person":[{"id":"jennifer-brown","kind":"person","name":"Jennifer R. Brown","route":"/people/jennifer-brown/"},{"id":"oyler-john","kind":"person","name":"John Oyler","route":"/people/oyler-john/"}],"pairing":[{"id":"btki-ibrutinib-cardiac-caution","kind":"pairing","name":"Caution: ibrutinib in patients with cardiac risk","route":"/pairings/btki-ibrutinib-cardiac-caution/"}],"paper":[{"id":"paper-zanubrutinib-cll-n-engl-j-med-2023","kind":"paper","name":"Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia","route":"/key-papers/paper-zanubrutinib-cll-n-engl-j-med-2023/"}]}}