{"id":"btk","name":"BTK (Bruton tyrosine 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LBCL","nct":"NCT03960840","phase":"1/2","status":"active"},{"id":"nct04502394","name":"Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With R/R DLBCL or R/R CLL","nct":"NCT04502394","phase":"1/2","status":"recruiting"},{"id":"nct04494503","name":"Study of APG2575 Single Agent and Combination Therapy in Patients With Relapsed/Refractory CLL/SLL","nct":"NCT04494503","phase":"1/2","status":"recruiting"},{"id":"nct07520006","name":"Study of NX-5948 in Combination With Other Agents in Adults With B-cell Malignancies","nct":"NCT07520006","phase":"1/2","status":"recruiting"},{"id":"nct05294731","name":"Treatment of Chinese Participants With B-Cell Malignancies With BGB-16673, a Bruton Tyrosine Kinase-Targeted Protein-Degrader","nct":"NCT05294731","phase":"1/2","status":"recruiting"},{"id":"nct03379428","name":"Trial of Ibrutinib Plus Trastuzumab in HER2-amplified Metastatic Breast Cancer","nct":"NCT03379428","phase":"1/2","status":"active"},{"id":"nct04274738","name":"A Study of Mavorixafor in Combination With Ibrutinib in Participants With Waldenstrom's Macroglobulinemia (WM) Whose Tumors Express Mutations in MYD88 and CXCR4","nct":"NCT04274738","phase":"1","status":"completed"}],"pathways":["inflammation-nfkb"],"companies":["abbvie","astrazeneca","beone","eli-lilly","innocare","johnson-johnson","merck","nurix"],"keyPapers":["paper-echo-acalabrutinib-bendamustine-rituximab-mantle-cell-jco-2025","paper-amplify-acalabrutinib-venetoclax-nejm-2025","paper-enrich-ibrutinib-rituximab-mantle-cell-lancet-2025","paper-rosewood-zanubrutinib-obinutuzumab-follicular-jco-2023","paper-shine-ibrutinib-bendamustine-rituximab-mantle-cell-nejm-2022","paper-elevate-tn-acalabrutinib-lancet-2020","paper-zuma-2-brexu-cel-mantle-cell-nejm-2020","paper-phoenix-ibrutinib-r-chop-non-gcb-dlbcl-jco-2019","paper-schmitz-genetics-pathogenesis-dlbcl-nejm-2018"],"hotspots":[{"label":"C481S / C481R / C481F","position":481,"kind":"resistance","frequency":"The dominant mutation at progression on covalent BTK inhibitors in CLL","drugs":["pirtobrutinib","nemtabrutinib","bgb-16673"]},{"label":"T474I (gatekeeper) and L528W (kinase-dead)","position":528,"kind":"resistance","drugs":["bgb-16673"]},{"label":"PLCG2 (downstream, not BTK)","position":659,"kind":"other","drugs":["venetoclax"]}],"openQuestions":[{"id":"btk-degrader-vs-inhibitor","question":"Do BTK degraders outperform non-covalent inhibitors once C481S, T474I or L528W mutations have appeared, and could they replace inhibitors in front line?","stage":"clinical","actor":"industry","source":{"label":"Woyach et al., NEJM 2014","url":"https://doi.org/10.1056/NEJMoa1400029"}}],"assays":[],"resistance":[{"class":"btk-inhibitor","mechanism":"BTK C481S","category":"on-target"},{"class":"btk-inhibitor","mechanism":"BTK L528W and T474I after a non-covalent 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