Phase 1 study of mTORC1/2 inhibitor sapanisertib (TAK-228) in advanced solid tumours, with an expansion phase in renal, endometrial or bladder cancer

Teràpia del càncer; Càncer ginecològic; Càncer urològic

Detalles Bibliográficos
Autores: Voss, Martin H., Gordon, Michael S., Mita, Monica, Rini, Brian, Makker, Vicky, Macarulla Mercadé, Teresa
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:11351/6503
Acceso en línea:https://hdl.handle.net/11351/6503
Access Level:acceso abierto
Palabra clave:Càncer - Tractament
Medicaments - Administració
DISEASES::Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Toxicity Tests::Maximum Tolerated Dose
ENFERMEDADES::neoplasias
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::pruebas de toxicidad::dosis máxima tolerada
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network_acronym_str ES
network_name_str España
repository_id_str
spelling Phase 1 study of mTORC1/2 inhibitor sapanisertib (TAK-228) in advanced solid tumours, with an expansion phase in renal, endometrial or bladder cancerVoss, Martin H.Gordon, Michael S.Mita, MonicaRini, BrianMakker, VickyMacarulla Mercadé, TeresaCàncer - TractamentMedicaments - AdministracióDISEASES::NeoplasmsOther subheadings::Other subheadings::Other subheadings::/drug therapyANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Toxicity Tests::Maximum Tolerated DoseENFERMEDADES::neoplasiasOtros calificadores::Otros calificadores::Otros calificadores::/farmacoterapiaTÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::pruebas de toxicidad::dosis máxima toleradaTeràpia del càncer; Càncer ginecològic; Càncer urològicTerapia del cáncer; Cáncer ginecológico; Cáncer urológicoCancer therapy; Gynaecological cancer; Urological cancerBackground This Phase 1 dose-escalation/expansion study assessed safety/tolerability of sapanisertib, an oral, highly selective inhibitor of mTORC1/mTORC2, in advanced solid tumours. Methods Eligible patients received increasing sapanisertib doses once daily (QD; 31 patients), once weekly (QW; 30 patients), QD for 3 days on/4 days off QW (QD × 3dQW; 33 patients) or QD for 5 days on/2 days off QW (QD × 5dQW; 22 patients). In expansion cohorts, 82 patients with renal cell carcinoma (RCC), endometrial or bladder cancer received sapanisertib 5 mg QD (39 patients), 40 mg QW (26 patients) or 30 mg QW (17 patients). Results Maximum tolerated doses of sapanisertib were 6 mg QD, 40 mg QW, 9 mg QD × 3dQW and 7 mg QD × 5dQW. Frequent dose-limiting toxicities (DLTs) included hyperglycaemia, maculo-papular rash (QD), asthenia and stomatitis (QD × 3dQW/QD × 5dQW); expansion phase doses of 5 mg QD and 30 mg QW were selected based on tolerability beyond the DLT evaluation period. One patient with RCC achieved complete response; nine experienced partial responses (RCC: seven patients; carcinoid tumour/endometrial cancer: one patient each). Sapanisertib pharmacokinetics were time-linear and supported multiple dosing. Pharmacodynamic findings demonstrated treatment-related reductions in TORC1/2 biomarkers. Conclusions Sapanisertib demonstrated a manageable safety profile, with preliminary antitumour activity observed in RCC and endometrial cancer.This study was supported by Millennium Pharmaceuticals Inc., Cambridge, MA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. NIH/NCI Cancer Center Support Grant (Memorial Sloan Kettering Cancer Center, P30 CA008748).Springer NatureInstitut Català de la Salut[Voss MH, Makker V] Department of Medicine, 300 East 66th Street, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. [Gordon MS] Oncology Research, HonorHealth Research Institute, 10510 N 92nd St Suite 200, Scottsdale, AZ 85258, USA. [Mita M] Department of Hematology and Oncology, Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, 8700 Beverly Blvd North Tower, Los Angeles, CA 90048, USA. [Rini B] Cleveland Clinic Foundation, Department of Solid Tumor Oncology, 9500 Euclid Avenue, Cleveland, OH 44195, USA. [Macarulla T] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, SpainVall d'Hebron Barcelona Hospital Campus202120212020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11351/6503Scientiareponame: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;123https://doi.org/10.1038/s41416-020-01041-xAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:11351/65032026-05-29T05:05:01Z
dc.title.none.fl_str_mv Phase 1 study of mTORC1/2 inhibitor sapanisertib (TAK-228) in advanced solid tumours, with an expansion phase in renal, endometrial or bladder cancer
title Phase 1 study of mTORC1/2 inhibitor sapanisertib (TAK-228) in advanced solid tumours, with an expansion phase in renal, endometrial or bladder cancer
spellingShingle Phase 1 study of mTORC1/2 inhibitor sapanisertib (TAK-228) in advanced solid tumours, with an expansion phase in renal, endometrial or bladder cancer
Voss, Martin H.
Càncer - Tractament
Medicaments - Administració
DISEASES::Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Toxicity Tests::Maximum Tolerated Dose
ENFERMEDADES::neoplasias
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::pruebas de toxicidad::dosis máxima tolerada
title_short Phase 1 study of mTORC1/2 inhibitor sapanisertib (TAK-228) in advanced solid tumours, with an expansion phase in renal, endometrial or bladder cancer
title_full Phase 1 study of mTORC1/2 inhibitor sapanisertib (TAK-228) in advanced solid tumours, with an expansion phase in renal, endometrial or bladder cancer
title_fullStr Phase 1 study of mTORC1/2 inhibitor sapanisertib (TAK-228) in advanced solid tumours, with an expansion phase in renal, endometrial or bladder cancer
title_full_unstemmed Phase 1 study of mTORC1/2 inhibitor sapanisertib (TAK-228) in advanced solid tumours, with an expansion phase in renal, endometrial or bladder cancer
title_sort Phase 1 study of mTORC1/2 inhibitor sapanisertib (TAK-228) in advanced solid tumours, with an expansion phase in renal, endometrial or bladder cancer
dc.creator.none.fl_str_mv Voss, Martin H.
Gordon, Michael S.
Mita, Monica
Rini, Brian
Makker, Vicky
Macarulla Mercadé, Teresa
author Voss, Martin H.
author_facet Voss, Martin H.
Gordon, Michael S.
Mita, Monica
Rini, Brian
Makker, Vicky
Macarulla Mercadé, Teresa
author_role author
author2 Gordon, Michael S.
Mita, Monica
Rini, Brian
Makker, Vicky
Macarulla Mercadé, Teresa
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Voss MH, Makker V] Department of Medicine, 300 East 66th Street, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. [Gordon MS] Oncology Research, HonorHealth Research Institute, 10510 N 92nd St Suite 200, Scottsdale, AZ 85258, USA. [Mita M] Department of Hematology and Oncology, Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, 8700 Beverly Blvd North Tower, Los Angeles, CA 90048, USA. [Rini B] Cleveland Clinic Foundation, Department of Solid Tumor Oncology, 9500 Euclid Avenue, Cleveland, OH 44195, USA. [Macarulla T] Servei d’Oncologia Mèdica, 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
Medicaments - Administració
DISEASES::Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Toxicity Tests::Maximum Tolerated Dose
ENFERMEDADES::neoplasias
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::pruebas de toxicidad::dosis máxima tolerada
topic Càncer - Tractament
Medicaments - Administració
DISEASES::Neoplasms
Other subheadings::Other subheadings::Other subheadings::/drug therapy
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Toxicity Tests::Maximum Tolerated Dose
ENFERMEDADES::neoplasias
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::pruebas de toxicidad::dosis máxima tolerada
description Teràpia del càncer; Càncer ginecològic; Càncer urològic
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/11351/6503
url https://hdl.handle.net/11351/6503
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv British Journal of Cancer;123
https://doi.org/10.1038/s41416-020-01041-x
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 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
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score 15.812429

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