dc.contributor
Institut Català de la Salut
dc.contributor
[Vieito M] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Simonelli M] Department of Biomedical Sciences, Humanitas University, Milan, Italy. IRCCS Humanitas Research Hospital, Milan, Italy. [de Vos F] Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. [Moreno V] START Madrid-FJD, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain. [Geurts M] Erasmus MC Cancer Institute, Rotterdam, the Netherlands. [Lorenzi E] IRCCS Humanitas Research Hospital, Milan, Italy
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Vieito Villar, Maria
dc.contributor.author
De Vos, Filip
dc.contributor.author
Marjolein Geurts
dc.contributor.author
Lorenzi, Elena
dc.contributor.author
Simonelli, Matteo
dc.contributor.author
Moreno, Victor
dc.date.accessioned
2025-10-25T05:38:09Z
dc.date.available
2025-10-25T05:38:09Z
dc.date.issued
2022-12-02T09:03:36Z
dc.date.issued
2022-12-02T09:03:36Z
dc.identifier
Vieito M, Simonelli M, de Vos F, Moreno V, Geurts M, Lorenzi E, et al. Trotabresib (CC-90010) in combination with adjuvant temozolomide or concomitant temozolomide plus radiotherapy in patients with newly diagnosed glioblastoma. Neurooncol Adv. 2022 Jan-Dec;4(1):vdac146.
dc.identifier
https://hdl.handle.net/11351/8583
dc.identifier
10.1093/noajnl/vdac146
dc.identifier.uri
http://hdl.handle.net/11351/8583
dc.description.abstract
BET inhibitors; Glioblastoma; Pharmacokinetics
dc.description.abstract
Inhibidores de BET; Glioblastoma; Farmacocinética
dc.description.abstract
Inhibidors de BET; Glioblastoma; Farmacocinètica
dc.description.abstract
Background
Standard-of-care treatment for newly diagnosed glioblastoma (ndGBM), consisting of surgery followed by radiotherapy (RT) and temozolomide (TMZ), has improved outcomes compared with RT alone; however, prognosis remains poor. Trotabresib, a novel bromodomain and extraterminal inhibitor, has demonstrated antitumor activity in patients with high-grade gliomas.
Methods
In this phase Ib, dose-escalation study (NCT04324840), we investigated trotabresib 15, 30, and 45 mg combined with TMZ in the adjuvant setting and trotabresib 15 and 30 mg combined with TMZ+RT in the concomitant setting in patients with ndGBM. Primary endpoints were to determine safety, tolerability, maximum tolerated dose, and/or recommended phase II dose (RP2D) of trotabresib. Secondary endpoints were assessment of preliminary efficacy and pharmacokinetics. Pharmacodynamics were investigated as an exploratory endpoint.
Results
The adjuvant and concomitant cohorts enrolled 18 and 14 patients, respectively. Trotabresib in combination with TMZ or TMZ+RT was well tolerated; most treatment-related adverse events were mild or moderate. Trotabresib pharmacokinetics and pharmacodynamics in both settings were consistent with previous data for trotabresib monotherapy. The RP2D of trotabresib was selected as 30 mg 4 days on/24 days off in both settings. At last follow-up, 5 (28%) and 6 (43%) patients remain on treatment in the adjuvant and concomitant settings, respectively, with 1 patient in the adjuvant cohort achieving complete response.
Conclusions
Trotabresib combined with TMZ in the adjuvant setting and with TMZ+RT in the concomitant setting was safe and well tolerated in patients with ndGBM, with encouraging treatment durations. Trotabresib 30 mg was established as the RP2D in both settings.
dc.description.abstract
This study was sponsored by Celgene, a Bristol Myers Squibb company.
dc.format
application/pdf
dc.publisher
Oxford University Press
dc.relation
Neuro-Oncology Advances;4(1)
dc.relation
https://doi.org/10.1093/noajnl/vdac146
dc.rights
Attribution 4.0 International
dc.rights
http://creativecommons.org/licenses/by/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Glioblastoma multiforme - Tractament
dc.subject
Glioblastoma multiforme - Radioteràpia
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Quimioteràpia combinada
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DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neoplasms, Neuroepithelial::Glioma::Astrocytoma::Glioblastoma
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Other subheadings::Other subheadings::/therapy
dc.subject
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols
dc.subject
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Radiotherapy
dc.subject
ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::neoplasias neuroepiteliales::glioma::astrocitoma::glioblastoma
dc.subject
Otros calificadores::Otros calificadores::/terapia
dc.subject
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada
dc.subject
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::radioterapia
dc.title
Trotabresib (CC-90010) in combination with adjuvant temozolomide or concomitant temozolomide plus radiotherapy in patients with newly diagnosed glioblastoma
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
