Phase I/II sequencing study of azacitidine, epacadostat, and pembrolizumab in advanced solid tumors

Cancer epigenetics; Cancer immunotherapy

Detalles Bibliográficos
Autores: Luke, Jason, Fakih, Marwan, Schneider, Charles, Chiorean, E. Gabriela, Bendell, Johanna, Kristeleit, Rebecca, Brana, Irene
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
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:11351/9837
Acceso en línea:https://hdl.handle.net/11351/9837
http://hdl.handle.net/11351/9837
Access Level:acceso abierto
Palabra clave:Càncer - Tractament
Càncer - Aspectes genètics
Medicaments antineoplàstics - Ús terapèutic
DISEASES::Neoplasms
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
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
id ES_1e6e5dffd290cd034f57171b71c0b3f7
oai_identifier_str oai:recercat.cat:11351/9837
network_acronym_str ES
network_name_str España
repository_id_str
spelling Phase I/II sequencing study of azacitidine, epacadostat, and pembrolizumab in advanced solid tumorsLuke, JasonFakih, MarwanSchneider, CharlesChiorean, E. GabrielaBendell, JohannaKristeleit, RebeccaBrana, IreneCàncer - TractamentCàncer - Aspectes genèticsMedicaments antineoplàstics - Ús terapèuticDISEASES::NeoplasmsOther subheadings::Other subheadings::Other subheadings::/drug therapyCHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic AgentsOther subheadings::Other subheadings::/therapeutic useENFERMEDADES::neoplasiasOtros calificadores::Otros calificadores::Otros calificadores::/farmacoterapiaCOMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicosOtros calificadores::Otros calificadores::/uso terapéuticoCancer epigenetics; Cancer immunotherapyEpigenética del cáncer; Inmunoterapia contra el cáncerEpigenètica del càncer; Immunoteràpia del càncerBackground Indoleamine 2,3-dioxygenase 1 (IDO1), an interferon-inducible enzyme, contributes to tumor immune intolerance. Immune checkpoint inhibition may increase interferon levels; combining IDO1 inhibition with immune checkpoint blockade represents an attractive strategy. Epigenetic agents trigger interferon responses and may serve as an immunotherapy priming method. We evaluated whether epigenetic therapy plus IDO1 inhibition and immune checkpoint blockade confers clinical benefit to patients with advanced solid tumors. Methods ECHO-206 was a Phase I/II study where treatment-experienced patients with advanced solid tumors (N = 70) received azacitidine plus an immunotherapy doublet (epacadostat [IDO1 inhibitor] and pembrolizumab). Sequencing of treatment was also assessed. Primary endpoints were safety/tolerability (Phase I), maximum tolerated dose (MTD) or pharmacologically active dose (PAD; Phase I), and investigator-assessed objective response rate (ORR; Phase II). Results In Phase I, no dose-limiting toxicities were reported, the MTD was not reached; a PAD was not determined. ORR was 5.7%, with four partial responses. The most common treatment-related adverse events (AEs) were fatigue (42.9%) and nausea (42.9%). Twelve (17.1%) patients experienced ≥1 fatal AE, one of which (asthenia) was treatment-related. Conclusions Although the azacitidine-epacadostat-pembrolizumab regimen was well tolerated, it was not associated with substantial clinical response in patients with advanced solid tumors previously exposed to immunotherapy.This study was sponsored by Incyte Corporation.Springer NatureInstitut Català de la Salut[Luke JJ] UPMC Hillman Cancer Center, Pittsburgh, PA, USA. [Fakih M] City of Hope Comprehensive Cancer Center, Duarte, CA, USA. [Schneider C] Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. [Chiorean EG] University of Washington School of Medicine, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. [Bendell J] Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN, USA. [Kristeleit R] Guy’s and St. Thomas’ NHS Foundation Trust, London, UK. [Kurzrock R] University of California San Diego School of Medicine, La Jolla, CA, USA. [Blagden SP] Early Phase Clinical Trials Unit, University of Oxford, Oxford, England, UK. [Brana I] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, SpainVall d'Hebron Barcelona Hospital Campus202320232023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttps://hdl.handle.net/11351/9837http://hdl.handle.net/11351/9837Scientiareponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésBritish Journal of Cancer;128https://doi.org/10.1038/s41416-023-02267-1Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:11351/98372026-05-29T05:05:01Z
dc.title.none.fl_str_mv Phase I/II sequencing study of azacitidine, epacadostat, and pembrolizumab in advanced solid tumors
title Phase I/II sequencing study of azacitidine, epacadostat, and pembrolizumab in advanced solid tumors
spellingShingle Phase I/II sequencing study of azacitidine, epacadostat, and pembrolizumab in advanced solid tumors
Luke, Jason
Càncer - Tractament
Càncer - Aspectes genètics
Medicaments antineoplàstics - Ús terapèutic
DISEASES::Neoplasms
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
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 Phase I/II sequencing study of azacitidine, epacadostat, and pembrolizumab in advanced solid tumors
title_full Phase I/II sequencing study of azacitidine, epacadostat, and pembrolizumab in advanced solid tumors
title_fullStr Phase I/II sequencing study of azacitidine, epacadostat, and pembrolizumab in advanced solid tumors
title_full_unstemmed Phase I/II sequencing study of azacitidine, epacadostat, and pembrolizumab in advanced solid tumors
title_sort Phase I/II sequencing study of azacitidine, epacadostat, and pembrolizumab in advanced solid tumors
dc.creator.none.fl_str_mv Luke, Jason
Fakih, Marwan
Schneider, Charles
Chiorean, E. Gabriela
Bendell, Johanna
Kristeleit, Rebecca
Brana, Irene
author Luke, Jason
author_facet Luke, Jason
Fakih, Marwan
Schneider, Charles
Chiorean, E. Gabriela
Bendell, Johanna
Kristeleit, Rebecca
Brana, Irene
author_role author
author2 Fakih, Marwan
Schneider, Charles
Chiorean, E. Gabriela
Bendell, Johanna
Kristeleit, Rebecca
Brana, Irene
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Luke JJ] UPMC Hillman Cancer Center, Pittsburgh, PA, USA. [Fakih M] City of Hope Comprehensive Cancer Center, Duarte, CA, USA. [Schneider C] Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. [Chiorean EG] University of Washington School of Medicine, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. [Bendell J] Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN, USA. [Kristeleit R] Guy’s and St. Thomas’ NHS Foundation Trust, London, UK. [Kurzrock R] University of California San Diego School of Medicine, La Jolla, CA, USA. [Blagden SP] Early Phase Clinical Trials Unit, University of Oxford, Oxford, England, UK. [Brana I] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv Càncer - Tractament
Càncer - Aspectes genètics
Medicaments antineoplàstics - Ús terapèutic
DISEASES::Neoplasms
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
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 Càncer - Tractament
Càncer - Aspectes genètics
Medicaments antineoplàstics - Ús terapèutic
DISEASES::Neoplasms
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
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 Cancer epigenetics; Cancer immunotherapy
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/11351/9837
http://hdl.handle.net/11351/9837
url https://hdl.handle.net/11351/9837
http://hdl.handle.net/11351/9837
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv British Journal of Cancer;128
https://doi.org/10.1038/s41416-023-02267-1
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
application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
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_ 1869404340386529280
score 15,81155

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