Phase 1b/2a study of galunisertib, a small molecule inhibitor of transforming growth factor-beta receptor I, in combination with standard temozolomide-based radiochemotherapy in patients with newly diagnosed malignant glioma

Biomarcadors; Glioblastoma; Radioqimioteràpia

Detalles Bibliográficos
Autores: Wick, Antje, Desjardins, Annick, Suárez Rodríguez, Cristina, Forsyth, Peter, Gueorguieva, Ivelina, Burkholder, Tiana, Rodon Ahnert, Jordi
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:11351/6463
Acceso en línea:https://hdl.handle.net/11351/6463
http://hdl.handle.net/11351/6463
Access Level:acceso abierto
Palabra clave:Gliomes
Cervell - Càncer - Quimioteràpia
Cervell - Càncer - Radioteràpia
DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neoplasms, Neuroepithelial::Glioma
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Combined Modality Therapy::Chemoradiotherapy
ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::neoplasias neuroepiteliales::glioma
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::tratamiento combinado::quimiorradioterapia
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dc.title.none.fl_str_mv Phase 1b/2a study of galunisertib, a small molecule inhibitor of transforming growth factor-beta receptor I, in combination with standard temozolomide-based radiochemotherapy in patients with newly diagnosed malignant glioma
title Phase 1b/2a study of galunisertib, a small molecule inhibitor of transforming growth factor-beta receptor I, in combination with standard temozolomide-based radiochemotherapy in patients with newly diagnosed malignant glioma
spellingShingle Phase 1b/2a study of galunisertib, a small molecule inhibitor of transforming growth factor-beta receptor I, in combination with standard temozolomide-based radiochemotherapy in patients with newly diagnosed malignant glioma
Wick, Antje
Gliomes
Cervell - Càncer - Quimioteràpia
Cervell - Càncer - Radioteràpia
DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neoplasms, Neuroepithelial::Glioma
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Combined Modality Therapy::Chemoradiotherapy
ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::neoplasias neuroepiteliales::glioma
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::tratamiento combinado::quimiorradioterapia
title_short Phase 1b/2a study of galunisertib, a small molecule inhibitor of transforming growth factor-beta receptor I, in combination with standard temozolomide-based radiochemotherapy in patients with newly diagnosed malignant glioma
title_full Phase 1b/2a study of galunisertib, a small molecule inhibitor of transforming growth factor-beta receptor I, in combination with standard temozolomide-based radiochemotherapy in patients with newly diagnosed malignant glioma
title_fullStr Phase 1b/2a study of galunisertib, a small molecule inhibitor of transforming growth factor-beta receptor I, in combination with standard temozolomide-based radiochemotherapy in patients with newly diagnosed malignant glioma
title_full_unstemmed Phase 1b/2a study of galunisertib, a small molecule inhibitor of transforming growth factor-beta receptor I, in combination with standard temozolomide-based radiochemotherapy in patients with newly diagnosed malignant glioma
title_sort Phase 1b/2a study of galunisertib, a small molecule inhibitor of transforming growth factor-beta receptor I, in combination with standard temozolomide-based radiochemotherapy in patients with newly diagnosed malignant glioma
dc.creator.none.fl_str_mv Wick, Antje
Desjardins, Annick
Suárez Rodríguez, Cristina
Forsyth, Peter
Gueorguieva, Ivelina
Burkholder, Tiana
Rodon Ahnert, Jordi
author Wick, Antje
author_facet Wick, Antje
Desjardins, Annick
Suárez Rodríguez, Cristina
Forsyth, Peter
Gueorguieva, Ivelina
Burkholder, Tiana
Rodon Ahnert, Jordi
author_role author
author2 Desjardins, Annick
Suárez Rodríguez, Cristina
Forsyth, Peter
Gueorguieva, Ivelina
Burkholder, Tiana
Rodon Ahnert, Jordi
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Wick A] Clinical Cooperation Unit Neuro-oncology, German Cancer Research Center, Heidelberg University Medical Center, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. [Desjardins A] The Preston Robert Tisch Brain Tumor Center at Duke, Duke University, Durham, NC, USA. [Suarez C] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Forsyth P] H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. [Gueorguieva I] Eli Lilly and Company, Erl Wood, UK 6 Eli Lilly and Company, Indianapolis, IN, USA. [Burkholder T] Eli Lilly and Company, Indianapolis, IN, USA. [Rodon J] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, U. T. M. D. Anderson Cancer Center, Houston, TX, USA
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv Gliomes
Cervell - Càncer - Quimioteràpia
Cervell - Càncer - Radioteràpia
DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neoplasms, Neuroepithelial::Glioma
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Combined Modality Therapy::Chemoradiotherapy
ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::neoplasias neuroepiteliales::glioma
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::tratamiento combinado::quimiorradioterapia
topic Gliomes
Cervell - Càncer - Quimioteràpia
Cervell - Càncer - Radioteràpia
DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neoplasms, Neuroepithelial::Glioma
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Combined Modality Therapy::Chemoradiotherapy
ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::neoplasias neuroepiteliales::glioma
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::tratamiento combinado::quimiorradioterapia
description Biomarcadors; Glioblastoma; Radioqimioteràpia
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
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/11351/6463
http://hdl.handle.net/11351/6463
url https://hdl.handle.net/11351/6463
http://hdl.handle.net/11351/6463
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Investigational New Drugs;38
https://doi.org/10.1007/s10637-020-00910-9
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
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
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
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spelling Phase 1b/2a study of galunisertib, a small molecule inhibitor of transforming growth factor-beta receptor I, in combination with standard temozolomide-based radiochemotherapy in patients with newly diagnosed malignant gliomaWick, AntjeDesjardins, AnnickSuárez Rodríguez, CristinaForsyth, PeterGueorguieva, IvelinaBurkholder, TianaRodon Ahnert, JordiGliomesCervell - Càncer - QuimioteràpiaCervell - Càncer - RadioteràpiaDISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neoplasms, Neuroepithelial::GliomaANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Combined Modality Therapy::ChemoradiotherapyENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::neoplasias neuroepiteliales::gliomaTÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::tratamiento combinado::quimiorradioterapiaBiomarcadors; Glioblastoma; RadioqimioteràpiaBiomarcadores; Glioblastoma; RadioquimioterapiaBiomarkers; Glioblastoma; RadiochemotherapyPurpose Galunisertib, a TGF-β inhibitor, has demonstrated antitumor effects in preclinical and radiographic responses in some patients with malignant glioma. This Phase 1b/2a trial investigated the clinical benefit of combining galunisertib with temozolomide-based radiochemotherapy (TMZ/RTX) in patients with newly diagnosed malignant glioma (NCT01220271). Methods This is an open-label, 2-arm Phase 1b/2a study (N = 56) of galunisertib (intermittent dosing: 14 days on/14 days off per cycle of 28 days) in combination with TMZ/RTX (n = 40), versus a control arm (TMZ/RTX, n = 16). The primary objective of Phase 1b was to determine the safe and tolerable Phase 2 dose of galunisertib. The primary objective of Phase 2a was to confirm the tolerability and pharmacodynamic profile of galunisertib with TMZ/RTX, and the secondary objectives included determining the efficacy and pharmacokinetic (PK) profile of galunisertib with TMZ/RTX in patients with glioblastoma. This study also characterized the changes in the major T-cell subsets during TMZ/RTX plus galunisertib treatment. Results In the Phase 2a study, efficacy results for patients treated with galunisertib plus TMZ/RTX or TMZ/RTX were: median overall survival (18.2 vs 17.9 months), median progression-free survival (7.6 vs 11.5 months), and disease control rate (80% [32/40] vs 56% [9/16] patients) respectively. PK profile of galunisertib plus TMZ/RTX regimen was consistent with previously published PK data of galunisertib. The overall safety profile across treatment arms was comparable. Conclusion No differences in efficacy, safety or pharmacokinetic variables were observed between the two treatment arms.Open Access funding provided by Projekt DEAL. This trial was funded by Eli Lilly and Company.SpringerInstitut Català de la Salut[Wick A] Clinical Cooperation Unit Neuro-oncology, German Cancer Research Center, Heidelberg University Medical Center, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. [Desjardins A] The Preston Robert Tisch Brain Tumor Center at Duke, Duke University, Durham, NC, USA. [Suarez C] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Forsyth P] H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. [Gueorguieva I] Eli Lilly and Company, Erl Wood, UK 6 Eli Lilly and Company, Indianapolis, IN, USA. [Burkholder T] Eli Lilly and Company, Indianapolis, IN, USA. [Rodon J] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, U. T. M. D. Anderson Cancer Center, Houston, TX, USAVall d'Hebron Barcelona Hospital Campus202120212020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11351/6463http://hdl.handle.net/11351/6463Scientiareponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésInvestigational New Drugs;38https://doi.org/10.1007/s10637-020-00910-9Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:11351/64632026-05-29T05:05:01Z
score 15.811543

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