{"entity":{"id":"aspen-wm","kind":"trial","name":"ASPEN (Waldenström macroglobulinaemia)","aka":["ASPEN","BGB-3111-302"],"tldr":"ASPEN compared two BTK inhibitors head to head in Waldenström macroglobulinaemia: zanubrutinib did not produce statistically more deep responses than ibrutinib, but it caused far fewer heart rhythm problems and other side effects, which is why many guidelines now prefer it.","summary":"ASPEN randomised 201 patients with MYD88-mutated Waldenström macroglobulinaemia to zanubrutinib or ibrutinib, the first head-to-head comparison of BTK inhibitors in any disease. The primary endpoint was the rate of complete or very good partial response. A third, non-randomised cohort treated MYD88 wild-type patients with zanubrutinib.\n\nThe rate of complete or very good partial response was numerically higher with zanubrutinib but the difference was not statistically significant, so the primary endpoint was not met. Zanubrutinib caused substantially less atrial fibrillation, bleeding, diarrhoea and hypertension, and fewer patients stopped it for toxicity. On the strength of efficacy and tolerability it was approved in the United States for Waldenström macroglobulinaemia in 2021. Not to be confused with the ASPEN trial of everolimus versus sunitinib in non-clear-cell kidney cancer.","status":"mixed","asOf":"2026-09-17","links":[{"label":"ClinicalTrials.gov NCT03053440","url":"https://clinicaltrials.gov/study/NCT03053440"}],"tags":["subtype-trials"],"related":[],"cancers":["waldenstrom","non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["zanubrutinib","ibrutinib"],"companies":["beone"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["constantine-tam"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03053440","phase":"3","setting":"Waldenström macroglobulinaemia with a MYD88 mutation, untreated or relapsed: zanubrutinib against ibrutinib, with a separate cohort of MYD88 wild-type disease on zanubrutinib","sponsor":"BeiGene (BeOne Medicines)","result":"Zanubrutinib did not significantly increase the complete or very good partial response rate over ibrutinib, but had markedly less cardiovascular and other toxicity; approved for Waldenström macroglobulinaemia in 2021.","yearReported":2020,"enrolled":201,"outcomes":[]},"route":"/trials/aspen-wm/","neighbours":{"cancer":[{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"waldenstrom","kind":"cancer","name":"Waldenström macroglobulinaemia","route":"/cancers/waldenstrom/"}],"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":"constantine-tam","kind":"person","name":"Constantine S. Tam","route":"/people/constantine-tam/"}]}}