{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:03:25Z","timestamp":1789506205832,"version":"build-2803163510"},"reference-count":45,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008349","name":"Boehringer Ingelheim International GmbH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100022752","name":"MSD Sharp and Dohme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100022752","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004337","name":"Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004337","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["esmoopen.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["ESMO Open"],"published-print":{"date-parts":[[2025,5]]},"DOI":"10.1016\/j.esmoop.2025.104499","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T22:18:15Z","timestamp":1744150695000},"page":"104499","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"title":["Final results from the phase Ia\/Ib study of the novel bromodomain and extra-terminal domain inhibitor, BI 894999, in patients with advanced solid tumors or diffuse large B-cell lymphoma"],"prefix":"10.1016","volume":"10","author":[{"given":"U.M.","family":"Lauer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Awada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Postel-Vinay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.I.","family":"Shapiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Thieblemont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.A.","family":"Piha-Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.K.","family":"Paik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.R.","family":"Shepard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.I.","family":"Docampo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Galot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Rottey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Sadrolhefazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Marzin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Musa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Sch\u00f6ffski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"31","key":"10.1016\/j.esmoop.2025.104499_bib1","doi-asserted-by":"crossref","first-page":"11365","DOI":"10.1073\/pnas.1411701111","article-title":"Blockade of oncogenic I\u03baB kinase activity in diffuse large B-cell lymphoma by bromodomain and extraterminal domain protein inhibitors","volume":"111","author":"Ceribelli","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"10.1016\/j.esmoop.2025.104499_bib2","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1158\/1078-0432.CCR-14-1561","article-title":"The BET bromodomain inhibitor OTX015 affects pathogenetic pathways in preclinical B-cell tumor models and synergizes with targeted drugs","volume":"21","author":"Boi","year":"2015","journal-title":"Clin Cancer Res"},{"issue":"5","key":"10.1016\/j.esmoop.2025.104499_bib3","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.molcel.2014.05.016","article-title":"The mechanisms behind the therapeutic activity of BET bromodomain inhibition","volume":"54","author":"Shi","year":"2014","journal-title":"Mol Cell"},{"issue":"2","key":"10.1016\/j.esmoop.2025.104499_bib4","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.cell.2013.03.036","article-title":"Selective inhibition of tumor oncogenes by disruption of super-enhancers","volume":"153","author":"Lov\u00e9n","year":"2013","journal-title":"Cell"},{"key":"10.1016\/j.esmoop.2025.104499_bib5","doi-asserted-by":"crossref","first-page":"e29","DOI":"10.1017\/S1462399411001992","article-title":"Bromodomains as therapeutic targets","volume":"13","author":"Muller","year":"2011","journal-title":"Expert Rev Mol Med"},{"issue":"7370","key":"10.1016\/j.esmoop.2025.104499_bib6","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/nature10334","article-title":"RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia","volume":"478","author":"Zuber","year":"2011","journal-title":"Nature"},{"issue":"3","key":"10.1016\/j.esmoop.2025.104499_bib7","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1158\/2159-8290.CD-12-0418","article-title":"Targeting MYCN in neuroblastoma by BET bromodomain inhibition","volume":"3","author":"Puissant","year":"2013","journal-title":"Cancer Discov"},{"issue":"22","key":"10.1016\/j.esmoop.2025.104499_bib8","doi-asserted-by":"crossref","first-page":"6183","DOI":"10.1158\/1078-0432.CCR-12-3904","article-title":"Efficacy of BET bromodomain inhibition in KRAS-mutant non\u2013small cell lung cancer","volume":"19","author":"Shimamura","year":"2013","journal-title":"Clin Cancer Res"},{"issue":"7327","key":"10.1016\/j.esmoop.2025.104499_bib9","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1038\/nature09504","article-title":"Selective inhibition of BET bromodomains","volume":"468","author":"Filippakopoulos","year":"2010","journal-title":"Nature"},{"issue":"1","key":"10.1016\/j.esmoop.2025.104499_bib10","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1475-2867-14-18","article-title":"The basal transcription machinery as a target for cancer therapy","volume":"14","author":"Villica\u00f1a","year":"2014","journal-title":"Cancer Cell Int"},{"issue":"6","key":"10.1016\/j.esmoop.2025.104499_bib11","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.ccr.2013.11.003","article-title":"Discovery and characterization of super-enhancer-associated dependencies in diffuse large B cell lymphoma","volume":"24","author":"Chapuy","year":"2013","journal-title":"Cancer Cell"},{"issue":"1","key":"10.1016\/j.esmoop.2025.104499_bib12","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1002\/med.21730","article-title":"Inhibitors of bromodomain and extra-terminal proteins for treating multiple human diseases","volume":"41","author":"Kulikowski","year":"2021","journal-title":"Med Res Rev"},{"issue":"3","key":"10.1016\/j.esmoop.2025.104499_bib13","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s41416-022-01815-5","article-title":"Therapeutic impact of BET inhibitor BI 894999 treatment: backtranslation from the clinic","volume":"127","author":"Tontsch-Grunt","year":"2022","journal-title":"Br J Cancer"},{"key":"10.1016\/j.esmoop.2025.104499_bib14","doi-asserted-by":"crossref","DOI":"10.1016\/j.pharmthera.2020.107479","article-title":"Make your best BET: the emerging role of BET inhibitor treatment in malignant tumors","volume":"208","author":"Bechter","year":"2020","journal-title":"Pharmacol Ther"},{"key":"10.1016\/j.esmoop.2025.104499_bib15","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.canlet.2018.02.018","article-title":"Synergistic activity of BET inhibitor BI 894999 with PLK inhibitor volasertib in AML in vitro and in vivo","volume":"421","author":"Tontsch-Grunt","year":"2018","journal-title":"Cancer Lett"},{"issue":"suppl 13","key":"10.1016\/j.esmoop.2025.104499_bib16","article-title":"Abstract 5194: Epigenomic and transcriptional profiling of CRC cell lines with distinct response patterns to the BET inhibitor BI 894999","volume":"79","author":"Savarese","year":"2019","journal-title":"Cancer Res"},{"key":"10.1016\/j.esmoop.2025.104499_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejca.2023.112987","article-title":"Phase Ia dose-escalation results for the BET protein inhibitor BI 894999 in patients with advanced or metastatic solid tumours","volume":"191","author":"Sch\u00f6ffski","year":"2023","journal-title":"Eur J Cancer"},{"issue":"1","key":"10.1016\/j.esmoop.2025.104499_bib18","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1038\/s41467-023-36976-1","article-title":"BET inhibitor trotabresib in heavily pretreated patients with solid tumors and diffuse large B-cell lymphomas","volume":"14","author":"Moreno","year":"2023","journal-title":"Nat Commun"},{"key":"10.1016\/j.esmoop.2025.104499_bib19","series-title":"A phase I study of GSK525762, a selective bromodomain (BRD) and extra terminal protein (BET) inhibitor: results from part 1 of phase I\/II open label single agent study in patients with acute myeloid leukemia (AML)","author":"Dawson","year":"2017"},{"key":"10.1016\/j.esmoop.2025.104499_bib20","doi-asserted-by":"crossref","first-page":"ii10","DOI":"10.1093\/annonc\/mdv085.3","article-title":"BET-bromodomain (BRD) inhibitor OTX015: final results of the dose-finding part of a phase I study in hematologic malignancies","volume":"26","author":"Herait","year":"2015","journal-title":"Ann Oncol"},{"issue":"13","key":"10.1016\/j.esmoop.2025.104499_bib21","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1038\/onc.2013.126","article-title":"MYC, a downstream target of BRD-NUT, is necessary and sufficient for the blockade of differentiation in NUT midline carcinoma","volume":"33","author":"Grayson","year":"2014","journal-title":"Oncogene"},{"issue":"2","key":"10.1016\/j.esmoop.2025.104499_bib22","doi-asserted-by":"crossref","DOI":"10.1093\/jncics\/pkz093","article-title":"Phase 1 study of molibresib (GSK525762), a bromodomain and extra-terminal domain protein inhibitor, in NUT carcinoma and other solid tumors","volume":"4","author":"Piha-Paul","year":"2020","journal-title":"JNCI Cancer Spectr"},{"issue":"12","key":"10.1016\/j.esmoop.2025.104499_bib23","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1080\/13543784.2017.1393518","article-title":"BET inhibitors in metastatic prostate cancer: therapeutic implications and rational drug combinations","volume":"26","author":"Markowski","year":"2017","journal-title":"Expert Opin Investig Drugs"},{"issue":"6","key":"10.1016\/j.esmoop.2025.104499_bib24","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1158\/1535-7163.MCT-15-0724","article-title":"Dual targeting of bromodomain and extraterminal domain proteins, and WNT or MAPK signaling, inhibits c-MYC expression and proliferation of colorectal cancer cells","volume":"15","author":"T\u00f6gel","year":"2016","journal-title":"Mol Cancer Ther"},{"key":"10.1016\/j.esmoop.2025.104499_bib25","doi-asserted-by":"crossref","DOI":"10.1016\/j.ctrv.2021.102154","article-title":"MYC as a target for cancer treatment","volume":"94","author":"Duffy","year":"2021","journal-title":"Cancer Treat Rev"},{"issue":"10","key":"10.1016\/j.esmoop.2025.104499_bib26","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1158\/1535-7163.MCT-15-0037","article-title":"Sensitivity of small cell lung cancer to BET inhibition is mediated by regulation of ASCL1 gene expression","volume":"14","author":"Lenhart","year":"2015","journal-title":"Mol Cancer Ther"},{"issue":"suppl 15","key":"10.1016\/j.esmoop.2025.104499_bib27","doi-asserted-by":"crossref","first-page":"2504","DOI":"10.1200\/JCO.2017.35.15_suppl.2504","article-title":"Abstract 2504: Phase I first-in-man trial of a novel bromodomain and extra-terminal domain (BET) inhibitor (BI 894999) in patients (Pts) with advanced solid tumors","volume":"35","author":"Aftimos","year":"2017","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.esmoop.2025.104499_bib28","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)","volume":"45(2)","author":"Eisenhauer","year":"2009","journal-title":"Eur J Cancer"},{"issue":"7","key":"10.1016\/j.esmoop.2025.104499_bib29","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1093\/annonc\/mdx097","article-title":"International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017)","volume":"28","author":"Younes","year":"2017","journal-title":"Ann Oncol"},{"issue":"2","key":"10.1016\/j.esmoop.2025.104499_bib30","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1158\/1535-7163.MCT-16-0475","article-title":"HEXIM1 as a robust pharmacodynamic marker for monitoring target engagement of BET family bromodomain inhibitors in tumors and surrogate tissues","volume":"16","author":"Lin","year":"2017","journal-title":"Mol Cancer Ther"},{"issue":"10","key":"10.1016\/j.esmoop.2025.104499_bib31","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20181551","article-title":"Cancer cell CCR2 orchestrates suppression of the adaptive immune response","volume":"217","author":"Fein","year":"2020","journal-title":"J Exp Med"},{"key":"10.1016\/j.esmoop.2025.104499_bib32","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2021.677646","article-title":"HIST2H2BF potentiates the propagation of cancer stem cells via notch signaling to promote malignancy and liver metastasis in colorectal carcinoma. Original Research","volume":"11","author":"Qiu","year":"2021","journal-title":"Front Oncol"},{"issue":"3","key":"10.1016\/j.esmoop.2025.104499_bib33","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1093\/bioinformatics\/btz647","article-title":"NACHO: an R package for quality control of NanoString nCounter data","volume":"36","author":"Canouil","year":"2020","journal-title":"Bioinformatics"},{"issue":"3","key":"10.1016\/j.esmoop.2025.104499_bib34","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1080\/10543409808835252","article-title":"Bayesian decision procedures based on logistic regression models for dose-finding studies","volume":"8","author":"Whitehead","year":"1998","journal-title":"J Biopharm Stat"},{"issue":"12","key":"10.1016\/j.esmoop.2025.104499_bib35","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1038\/s41416-020-01079-x","article-title":"Bromodomain inhibitors a decade later: a promise unfulfilled?","volume":"123","author":"Mita","year":"2020","journal-title":"Br J Cancer"},{"issue":"18","key":"10.1016\/j.esmoop.2025.104499_bib36","doi-asserted-by":"crossref","first-page":"3979","DOI":"10.1158\/1078-0432.CCR-22-0175","article-title":"Phase Ib study of the BET inhibitor GS-5829 as monotherapy and combined with enzalutamide in patients with metastatic castration-resistant prostate cancer","volume":"28","author":"Aggarwal","year":"2022","journal-title":"Clin Cancer Res"},{"issue":"6","key":"10.1016\/j.esmoop.2025.104499_bib37","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1002\/ijc.33861","article-title":"Safety, pharmacokinetic, pharmacodynamic and clinical activity of molibresib for the treatment of nuclear protein in testis carcinoma and other cancers: results of a Phase I\/II open-label, dose escalation study","volume":"150","author":"Cousin","year":"2022","journal-title":"Int J Cancer"},{"issue":"7","key":"10.1016\/j.esmoop.2025.104499_bib38","doi-asserted-by":"crossref","first-page":"3043","DOI":"10.3390\/molecules28073043","article-title":"BET bromodomain inhibitors: novel design strategies and therapeutic applications","volume":"28","author":"To","year":"2023","journal-title":"Molecules"},{"issue":"8","key":"10.1016\/j.esmoop.2025.104499_bib39","doi-asserted-by":"crossref","DOI":"10.1097\/HS9.0000000000000610","article-title":"The novel oral BET-CBP\/p300 dual inhibitor NEO2734 is highly effective in eradicating acute myeloid leukemia blasts and stem\/progenitor cells","volume":"5","author":"van Gils","year":"2021","journal-title":"Hemasphere"},{"issue":"3","key":"10.1016\/j.esmoop.2025.104499_bib40","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.18632\/oncotarget.6309","article-title":"Concomitant BET and MAPK blockade for effective treatment of ovarian cancer","volume":"7","author":"Jing","year":"2016","journal-title":"Oncotarget"},{"issue":"3","key":"10.1016\/j.esmoop.2025.104499_bib41","first-page":"1069","article-title":"TNKS inhibitors potentiate proliferative inhibition of BET inhibitors via reducing \u03b2-Catenin in colorectal cancer cells","volume":"12","author":"Wu","year":"2022","journal-title":"Am J Cancer Res"},{"issue":"5","key":"10.1016\/j.esmoop.2025.104499_bib42","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.156657","article-title":"mTOR inhibition overcomes RSK3-mediated resistance to BET inhibitors in small cell lung cancer","volume":"8","author":"Kumari","year":"2023","journal-title":"JCI Insight"},{"issue":"1","key":"10.1016\/j.esmoop.2025.104499_bib43","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/s41392-023-01647-6","article-title":"Bromodomain and extraterminal (BET) proteins: biological functions, diseases and targeted therapy","volume":"8","author":"Wang","year":"2023","journal-title":"Signal Transduct Target Ther"},{"issue":"22","key":"10.1016\/j.esmoop.2025.104499_bib44","doi-asserted-by":"crossref","first-page":"4762","DOI":"10.1182\/bloodadvances.2021004619","article-title":"Phase 1b study of the BET protein inhibitor RO6870810 with venetoclax and rituximab in patients with diffuse large B-cell lymphoma","volume":"5","author":"Dickinson","year":"2021","journal-title":"Blood Adv"},{"issue":"16","key":"10.1016\/j.esmoop.2025.104499_bib45","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1002\/cncr.33590","article-title":"A phase 1 study of the pan-bromodomain and extraterminal inhibitor mivebresib (ABBV-075) alone or in combination with venetoclax in patients with relapsed\/refractory acute myeloid leukemia","volume":"127","author":"Borthakur","year":"2021","journal-title":"Cancer"}],"container-title":["ESMO Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2059702925003680?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2059702925003680?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T07:45:18Z","timestamp":1757576718000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2059702925003680"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5]]},"references-count":45,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["S2059702925003680"],"URL":"https:\/\/doi.org\/10.1016\/j.esmoop.2025.104499","relation":{},"ISSN":["2059-7029"],"issn-type":[{"value":"2059-7029","type":"print"}],"subject":[],"published":{"date-parts":[[2025,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Final results from the phase Ia\/Ib study of the novel bromodomain and extra-terminal domain inhibitor, BI 894999, in patients with advanced solid tumors or diffuse large B-cell lymphoma","name":"articletitle","label":"Article Title"},{"value":"ESMO Open","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.esmoop.2025.104499","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Ltd on behalf of European Society for Medical Oncology.","name":"copyright","label":"Copyright"}],"article-number":"104499"}}