{"entity":{"id":"bgb-16673","kind":"drug","name":"BGB-16673","aka":[],"tldr":"Instead of blocking BTK, this pill destroys it, so it works even when the enzyme has mutated to escape every inhibitor.","summary":"Chimeric degradation-activating compound recruiting an E3 ligase to BTK. CaDAnCe-101 (phase 1, relapsed CLL/SLL after covalent BTKi, many with BTK mutations): ORR 86% in 66 patients with a manageable profile (fatigue, bruising, diarrhoea, neutropenia), updated at EHA 2026. Phase 3 CaDAnCe-304 (~500 patients) compares BGB-16673 with pirtobrutinib after covalent BTKi. The first BTK degrader in phase 3.","status":"phase-3","asOf":"2026-09-07","links":[{"label":"CaDAnCe-304 design (Blood 2025)","url":"https://ashpublications.org/blood/article/146/Supplement%201/5691/550156/CaDAnCe-304-a-phase-3-open-label-randomized-study"}],"tags":[],"related":[],"cancers":["cll","dlbcl"],"sections":[],"technologies":["protac-degrader"],"targets":["btk"],"drugs":[],"companies":["beone"],"institutions":[],"pathways":[],"terms":[],"trials":["cadance-304","nct05006716","nct05294731","nct06970743"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"modality":"Small-molecule BTK degrader (CDAC)","mechanism":"Heterobifunctional degrader: one end binds BTK (wild-type or C481/T474/L528 mutant), the other recruits an E3 ligase, tagging BTK for proteasomal destruction.","approvals":[],"mechanismSteps":["BGB-16673 bridges BTK and an E3 ubiquitin ligase","BTK is ubiquitinated and destroyed by the proteasome","Both kinase and scaffolding functions of BTK are removed","Resistance mutations that block inhibitors do not prevent degradation"],"dosing":{"route":"Oral","schedule":"200 mg once daily (recommended phase 2 dose), continuous","monitoring":"Neutropenia, infections, bleeding"},"toxicity":[{"event":"Fatigue","anyGradePct":25,"source":"https://cllsociety.org/2026/03/btk-degrader-shows-promise-for-relapsed-cll/","note":"≥25% in CaDAnCe-101"},{"event":"Contusion/bruising","anyGradePct":25},{"event":"Neutropenia","anyGradePct":25}],"access":[],"regulatoryEvents":[]},"route":"/drugs/bgb-16673/","neighbours":{"cancer":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"mantle-cell-lymphoma","kind":"cancer","name":"Mantle cell lymphoma","route":"/cancers/mantle-cell-lymphoma/"}],"technology":[{"id":"protac-degrader","kind":"technology","name":"PROTACs & molecular glues (targeted protein degradation)","route":"/technologies/protac-degrader/"}],"target":[{"id":"btk","kind":"target","name":"BTK (Bruton tyrosine kinase)","route":"/targets/btk/"}],"company":[{"id":"beone","kind":"company","name":"BeOne Medicines (formerly BeiGene)","route":"/companies/beone/"}],"trial":[{"id":"nct05006716","kind":"trial","name":"A Dose-Escalation and Expansion Study of Tacabrutideg (BGB-16673) in Participants With B-Cell Malignancies","route":"/trials/nct05006716/"},{"id":"nct06970743","kind":"trial","name":"A Study of BGB-16673 Compared to Investigator's Choice in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Previously Exposed to Covalent Bruton Tyrosine Kinase (BTK) Inhibitors","route":"/trials/nct06970743/"},{"id":"cadance-304","kind":"trial","name":"CaDAnCe-304","route":"/trials/cadance-304/"},{"id":"nct05294731","kind":"trial","name":"Treatment of Chinese Participants With B-Cell Malignancies With BGB-16673, a Bruton Tyrosine Kinase-Targeted Protein-Degrader","route":"/trials/nct05294731/"}],"idea":[{"id":"idea-btk-degrader-frontline","kind":"idea","name":"BTK degraders to pre-empt resistance in frontline CLL","route":"/ideas/idea-btk-degrader-frontline/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"}],"pathway":[{"id":"ubiquitin-proteasome-system","kind":"pathway","name":"Ubiquitin-proteasome system & protein homeostasis","route":"/pathways/ubiquitin-proteasome-system/"}]}}