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

B-cell lymphoma; Cancer therapy; CNS cancer

Detalhes bibliográficos
Autores: Vieito Villar, Maria, Sepúlveda, Juan Manuel, Galvao De Aquiar, Vladimir, Hernández-Guerrero, T., Doger, B., Saavedra Gadea, Omar, Carpio Segura, Cecilia Carmen, Braña Garcia, Irene, Moreno, Victor
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2023
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:11351/9252
Acesso em linha:https://hdl.handle.net/11351/9252
Access Level:Acceso aberto
Palavra-chave:Cèl·lules B - Tumors - Tractament
Medicaments antineoplàstics - Ús terapèutic
DISEASES::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, B-Cell::Lymphoma, Large B-Cell, Diffuse
Other subheadings::Other subheadings::Other subheadings::/drug therapy
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents
Other subheadings::Other subheadings::/therapeutic use
ENFERMEDADES::neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células B::linfoma de células B grandes difuso
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos
Otros calificadores::Otros calificadores::/uso terapéutico
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oai_identifier_str oai:recercat.cat:11351/9252
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv BET inhibitor trotabresib in heavily pretreated patients with solid tumors and diffuse large B-cell lymphomas
title BET inhibitor trotabresib in heavily pretreated patients with solid tumors and diffuse large B-cell lymphomas
spellingShingle BET inhibitor trotabresib in heavily pretreated patients with solid tumors and diffuse large B-cell lymphomas
Vieito Villar, Maria
Cèl·lules B - Tumors - Tractament
Medicaments antineoplàstics - Ús terapèutic
DISEASES::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, B-Cell::Lymphoma, Large B-Cell, Diffuse
Other subheadings::Other subheadings::Other subheadings::/drug therapy
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents
Other subheadings::Other subheadings::/therapeutic use
ENFERMEDADES::neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células B::linfoma de células B grandes difuso
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos
Otros calificadores::Otros calificadores::/uso terapéutico
title_short BET inhibitor trotabresib in heavily pretreated patients with solid tumors and diffuse large B-cell lymphomas
title_full BET inhibitor trotabresib in heavily pretreated patients with solid tumors and diffuse large B-cell lymphomas
title_fullStr BET inhibitor trotabresib in heavily pretreated patients with solid tumors and diffuse large B-cell lymphomas
title_full_unstemmed BET inhibitor trotabresib in heavily pretreated patients with solid tumors and diffuse large B-cell lymphomas
title_sort BET inhibitor trotabresib in heavily pretreated patients with solid tumors and diffuse large B-cell lymphomas
dc.creator.none.fl_str_mv Vieito Villar, Maria
Sepúlveda, Juan Manuel
Galvao De Aquiar, Vladimir
Hernández-Guerrero, T.
Doger, B.
Saavedra Gadea, Omar
Carpio Segura, Cecilia Carmen
Braña Garcia, Irene
Moreno, Victor
author Vieito Villar, Maria
author_facet Vieito Villar, Maria
Sepúlveda, Juan Manuel
Galvao De Aquiar, Vladimir
Hernández-Guerrero, T.
Doger, B.
Saavedra Gadea, Omar
Carpio Segura, Cecilia Carmen
Braña Garcia, Irene
Moreno, Victor
author_role author
author2 Sepúlveda, Juan Manuel
Galvao De Aquiar, Vladimir
Hernández-Guerrero, T.
Doger, B.
Saavedra Gadea, Omar
Carpio Segura, Cecilia Carmen
Braña Garcia, Irene
Moreno, Victor
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Moreno V, Hernández-Guerrero T, Doger B] START Madrid-FJD, Hospital Universitario Fundación Jimenez Diaz, Madrid, Spain. [Vieito M, Galvao V, Saavedra O, Carpio C, Braña I] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Sepulveda JM] Hospital Universitario 12 de Octubre, Madrid, Spain
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv Cèl·lules B - Tumors - Tractament
Medicaments antineoplàstics - Ús terapèutic
DISEASES::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, B-Cell::Lymphoma, Large B-Cell, Diffuse
Other subheadings::Other subheadings::Other subheadings::/drug therapy
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents
Other subheadings::Other subheadings::/therapeutic use
ENFERMEDADES::neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células B::linfoma de células B grandes difuso
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos
Otros calificadores::Otros calificadores::/uso terapéutico
topic Cèl·lules B - Tumors - Tractament
Medicaments antineoplàstics - Ús terapèutic
DISEASES::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, B-Cell::Lymphoma, Large B-Cell, Diffuse
Other subheadings::Other subheadings::Other subheadings::/drug therapy
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents
Other subheadings::Other subheadings::/therapeutic use
ENFERMEDADES::neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células B::linfoma de células B grandes difuso
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos
Otros calificadores::Otros calificadores::/uso terapéutico
description B-cell lymphoma; Cancer therapy; CNS cancer
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11351/9252
url https://hdl.handle.net/11351/9252
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nature Communications;14
https://doi.org/10.1038/s41467-023-36976-1
dc.rights.none.fl_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Portfolio
publisher.none.fl_str_mv Nature Portfolio
dc.source.none.fl_str_mv Scientia
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869423889308712960
spelling BET inhibitor trotabresib in heavily pretreated patients with solid tumors and diffuse large B-cell lymphomasVieito Villar, MariaSepúlveda, Juan ManuelGalvao De Aquiar, VladimirHernández-Guerrero, T.Doger, B.Saavedra Gadea, OmarCarpio Segura, Cecilia CarmenBraña Garcia, IreneMoreno, VictorCèl·lules B - Tumors - TractamentMedicaments antineoplàstics - Ús terapèuticDISEASES::Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, B-Cell::Lymphoma, Large B-Cell, DiffuseOther subheadings::Other subheadings::Other subheadings::/drug therapyCHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic AgentsOther subheadings::Other subheadings::/therapeutic useENFERMEDADES::neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células B::linfoma de células B grandes difusoOtros calificadores::Otros calificadores::Otros calificadores::/farmacoterapiaCOMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicosOtros calificadores::Otros calificadores::/uso terapéuticoB-cell lymphoma; Cancer therapy; CNS cancerLimfoma de cèl·lules B; Teràpia del càncer; Càncer del SNCLinfoma de células B; Terapia del cáncer; Cáncer del SNCBromodomain 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.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.Nature PortfolioInstitut Català de la Salut[Moreno V, Hernández-Guerrero T, Doger B] START Madrid-FJD, Hospital Universitario Fundación Jimenez Diaz, Madrid, Spain. [Vieito M, Galvao V, Saavedra O, Carpio C, Braña I] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Sepulveda JM] Hospital Universitario 12 de Octubre, Madrid, SpainVall d'Hebron Barcelona Hospital Campus202320232023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfapplication/pdfhttps://hdl.handle.net/11351/9252Scientiareponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésNature Communications;14https://doi.org/10.1038/s41467-023-36976-1Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:11351/92522026-05-29T05:05:01Z
score 15.812429

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