{"entity":{"id":"btki-plus-venetoclax-fixed-duration","kind":"pairing","name":"BTK inhibitor + venetoclax, fixed duration","aka":[],"tldr":"Block the survival signal and remove the death shield at the same time, for about a year, then stop and stay in remission for years.","summary":"CAPTIVATE and GLOW (ibrutinib), AMPLIFY (acalabrutinib; FDA approved February 2026), SEQUOIA arm D (zanubrutinib), and CELESTIAL (sonrotoclax + zanubrutinib) all show high uMRD and durable PFS after 12-15 months of therapy. Fixed duration reduces cumulative toxicity and cost versus indefinite BTK inhibition.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03836261: AMPLIFY","url":"https://clinicaltrials.gov/study/NCT03836261"},{"label":"ClinicalTrials.gov NCT03462719: GLOW","url":"https://clinicaltrials.gov/study/NCT03462719"}],"tags":[],"related":[],"cancers":["cll"],"sections":[],"technologies":[],"targets":["btk","bcl2"],"drugs":["acalabrutinib","ibrutinib","zanubrutinib","venetoclax","sonrotoclax"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["amplify","glow","captivate","sequoia","celestial-tncll"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"acalabrutinib","b":"venetoclax","rationale":"BTK inhibition mobilises CLL cells out of protective lymph-node niches and increases BCL-2 dependence; venetoclax then kills them. The two resistance mechanisms are independent.","evidence":"Multiple positive phase 3 trials; US approval 2026.","pairingType":"combination"},"route":"/pairings/btki-plus-venetoclax-fixed-duration/","neighbours":{"cancer":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"cll-treatment-naive","kind":"cancer","name":"Chronic lymphocytic leukaemia, first treatment","route":"/cancers/cll-treatment-naive/"}],"target":[{"id":"bcl2","kind":"target","name":"BCL-2","route":"/targets/bcl2/"},{"id":"btk","kind":"target","name":"BTK (Bruton tyrosine kinase)","route":"/targets/btk/"}],"drug":[{"id":"acalabrutinib","kind":"drug","name":"Acalabrutinib","route":"/drugs/acalabrutinib/"},{"id":"ibrutinib","kind":"drug","name":"Ibrutinib","route":"/drugs/ibrutinib/"},{"id":"sonrotoclax","kind":"drug","name":"Sonrotoclax","route":"/drugs/sonrotoclax/"},{"id":"venetoclax","kind":"drug","name":"Venetoclax","route":"/drugs/venetoclax/"},{"id":"zanubrutinib","kind":"drug","name":"Zanubrutinib","route":"/drugs/zanubrutinib/"}],"trial":[{"id":"amplify","kind":"trial","name":"AMPLIFY","route":"/trials/amplify/"},{"id":"captivate","kind":"trial","name":"CAPTIVATE","route":"/trials/captivate/"},{"id":"celestial-tncll","kind":"trial","name":"CELESTIAL-TNCLL","route":"/trials/celestial-tncll/"},{"id":"glow","kind":"trial","name":"GLOW","route":"/trials/glow/"},{"id":"sequoia","kind":"trial","name":"SEQUOIA","route":"/trials/sequoia/"}],"paper":[{"id":"paper-amplify-acalabrutinib-venetoclax-nejm-2025","kind":"paper","name":"AMPLIFY: fixed-duration acalabrutinib plus venetoclax, with or without obinutuzumab, versus chemo-immunotherapy in fit CLL patients","route":"/key-papers/paper-amplify-acalabrutinib-venetoclax-nejm-2025/"}]}}