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BET inhibitor trotabresib in heavily pretreated patients with solid tumors and diffuse large B-cell lymphomas

dc.contributor.authorMoreno, V.*
dc.contributor.authorVieito Amor, Maria*
dc.contributor.authorSepulveda, J.M.*
dc.contributor.authorGalvao, V.*
dc.contributor.authorHernández-Guerrero, T.*
dc.contributor.authorDoger, B.*
dc.contributor.authorSaavedra, O.*
dc.contributor.authorCarlo-Stella, C.*
dc.contributor.authorMichot, J.-M.*
dc.contributor.authorItaliano, A.*
dc.contributor.authorMagagnoli, M.*
dc.contributor.authorCarpio, C.*
dc.contributor.authorPinto, A.*
dc.contributor.authorSarmiento, R.*
dc.contributor.authorAmoroso, B.*
dc.contributor.authorAronchik, I.*
dc.contributor.authorFilvaroff, E.*
dc.contributor.authorHanna, B.*
dc.contributor.authorWei, X.*
dc.contributor.authorNikolova, Z.*
dc.contributor.authorBraña, I.*
dc.date.accessioned2025-09-08T11:44:55Z
dc.date.available2025-09-08T11:44:55Z
dc.date.issued2023
dc.identifier.citationMoreno V, Vieito M, Sepulveda JM, Galvao V, Hernández-Guerrero T, Doger B, et al. BET inhibitor trotabresib in heavily pretreated patients with solid tumors and diffuse large B-cell lymphomas. Nature communications. 2023;14(1):1359.
dc.identifier.issn2041-1723
dc.identifier.otherhttps://portalcientifico.sergas.gal//documentos/642b380aa1c8a315fd234773
dc.identifier.urihttp://hdl.handle.net/20.500.11940/21145
dc.description.abstractBromodomain and extraterminal proteins (BET) play key roles in regulation of gene expression, and may play a role in cancer-cell proliferation, survival, and oncogenic progression. CC-90010-ST-001 (NCT03220347) is an open-label phase I study of trotabresib, an oral BET inhibitor, in heavily pretreated patients with advanced solid tumors and relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Primary endpoints were the safety, tolerability, maximum tolerated dose, and RP2D of trotabresib. Secondary endpoints were clinical benefit rate (complete response [CR] + partial response [PR] + stable disease [SD] of ?4 months' duration), objective response rate (CR + PR), duration of response or SD, progression-free survival, overall survival, and the pharmacokinetics (PK) of trotabresib. In addition, part C assessed the effects of food on the PK of trotabresib as a secondary endpoint. The dose escalation (part A) showed that trotabresib was well tolerated, had single-agent activity, and determined the recommended phase 2 dose (RP2D) and schedule for the expansion study. Here, we report long-term follow-up results from part A (N = 69) and data from patients treated with the RP2D of 45 mg/day 4 days on/24 days off or an alternate RP2D of 30 mg/day 3 days on/11 days off in the dose-expansion cohorts (parts B [N = 25] and C [N = 41]). Treatment-related adverse events (TRAEs) are reported in almost all patients. The most common severe TRAEs are hematological. Toxicities are generally manageable, allowing some patients to remain on treatment for ?2 years, with two patients receiving ?3 years of treatment. Trotabresib monotherapy shows antitumor activity, with an ORR of 13.0% (95% CI, 2.8-33.6) in patients with R/R DLBCL (part B) and an ORR of 0.0% (95% CI, 0.0-8.6) and a CBR of 31.7% (95% CI, 18.1-48.1) in patients with advanced solid tumors (part C). These results support further investigation of trotabresib in combination with other anticancer agents.
dc.description.sponsorshipThe authors thank the patients and their families who made this study possible and the clinical study teams who participated in the study. The authors also thank Olga Ferrero, the primary research nurse for the study, and Esther Chan for assistance with pharmacodynamic analyses. This study was sponsored by Celgene, a Bristol Myers Squibb Company. The study sponsor was involved in the study design, analysis of data, and writing the manuscript. Medical writing and editorial assistance were provided by Bernard Kerr, PGDipSci, and Agata Shodeke, of Spark, funded by Bristol Myers Squibb.
dc.languageeng
dc.rightsAttribution 4.0 International (CC BY 4.0)*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.meshHumans *
dc.subject.meshAntineoplastic Agents *
dc.subject.meshLymphoma, Large B-Cell, Diffuse *
dc.subject.meshLymphoma, Non-Hodgkin *
dc.titleBET inhibitor trotabresib in heavily pretreated patients with solid tumors and diffuse large B-cell lymphomas
dc.typeArtigo
dc.authorsophosMoreno, V.; Vieito, M.; Sepulveda, J.M.; Galvao, V.; Hernández-Guerrero, T.; Doger, B.; Saavedra, O.; Carlo-Stella, C.; Michot, J.-M.; Italiano, A.; Magagnoli, M.; Carpio, C.; Pinto, A.; Sarmiento, R.; Amoroso, B.; Aronchik, I.; Filvaroff, E.; Hanna, B.; Wei, X.; Nikolova, Z.; Braña, I.
dc.identifier.doi10.1038/s41467-023-36976-1
dc.identifier.sophos642b380aa1c8a315fd234773
dc.issue.number1
dc.journal.titleNature communications*
dc.organizationServizo Galego de Saúde::Áreas Sanitarias (A.S.) - Complexo Hospitalario Universitario de Vigo::Anestesioloxía e reanimación
dc.page.initial1359
dc.relation.projectIDCelgene
dc.relation.projectIDBristol Myers Squibb Company
dc.relation.projectIDBristol Myers Squibb
dc.relation.publisherversionhttps://doi.org/10.1038/s41467-023-36976-1
dc.rights.accessRightsopenAccess*
dc.subject.keywordAS Vigo
dc.subject.keywordCHUVI
dc.typefidesArtículo Científico (incluye Original, Original breve, Revisión Sistemática y Meta-análisis)
dc.typesophosArtículo Original
dc.volume.number14


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