dc.contributor
Institut Català de la Salut
dc.contributor
[van den Bent M] Erasmus University Medical Center (MC) Cancer Institute, Rotterdam, The Netherlands. [Azaro A] Unitat d’Investigació de Teràpia Molecular, Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [De Vos F] University Medical Center Utrecht, Utrecht, The Netherlands. [Sepulveda J] Hospital Universitario, 12 de Octubre, Madrid, Spain. [Yung WKA] MD Anderson Cancer Center, Houston, TX, USA. [Wen PY] Center for Neuro-Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Azaro Pedrazzoli, Analía Beatriz
dc.contributor.author
De Vos, Filip
dc.contributor.author
Sepúlveda, Juan Manuel
dc.contributor.author
Yung, W. K. Alfred
dc.contributor.author
Wen, Patrick Y.
dc.contributor.author
van den Bent, Martin
dc.date.accessioned
2025-10-24T10:44:45Z
dc.date.available
2025-10-24T10:44:45Z
dc.date.issued
2021-10-22T11:40:36Z
dc.date.issued
2021-10-22T11:40:36Z
dc.identifier
van den Bent M, Azaro A, De Vos F, Sepulveda J, Yung WKA, Wen PY, et al. A Phase Ib/II, open-label, multicenter study of INC280 (capmatinib) alone and in combination with buparlisib (BKM120) in adult patients with recurrent glioblastoma. J Neurooncol. 2020 Jan;146:79–89.
dc.identifier
https://hdl.handle.net/11351/6452
dc.identifier
10.1007/s11060-019-03337-2
dc.identifier
000500801900001
dc.identifier.uri
https://hdl.handle.net/11351/6452
dc.description.abstract
Buparlisib; Capmatinib; Glioblastoma
dc.description.abstract
Buparlisib; Capmatinib; Glioblastoma
dc.description.abstract
Buparlisib; Capmatinib; Glioblastoma
dc.description.abstract
Purpose
To estimate the maximum tolerated dose (MTD) and/or identify the recommended Phase II dose (RP2D) for combined INC280 and buparlisib in patients with recurrent glioblastoma with homozygous phosphatase and tensin homolog (PTEN) deletion, mutation or protein loss.
Methods
This multicenter, open-label, Phase Ib/II study included adult patients with glioblastoma with mesenchymal-epithelial transcription factor (c-Met) amplification. In Phase Ib, patients received INC280 as capsules or tablets in combination with buparlisib. In Phase II, patients received INC280 only. Response was assessed centrally using Response Assessment in Neuro-Oncology response criteria for high-grade gliomas. All adverse events (AEs) were recorded and graded.
Results
33 patients entered Phase Ib, 32 with altered PTEN. RP2D was not declared due to potential drug–drug interactions, which may have resulted in lack of efficacy; thus, Phase II, including 10 patients, was continued with INC280 monotherapy only. Best response was stable disease in 30% of patients. In the selected patient population, enrollment was halted due to limited activity with INC280 monotherapy. In Phase Ib, the most common treatment-related AEs were fatigue (36.4%), nausea (30.3%) and increased alanine aminotransferase (30.3%). MTD was identified at INC280 Tab 300 mg twice daily + buparlisib 80 mg once daily. In Phase II, the most common AEs were headache (40.0%), constipation (30.0%), fatigue (30.0%) and increased lipase (30.0%).
Conclusion
The combination of INC280/buparlisib resulted in no clear activity in patients with recurrent PTEN-deficient glioblastoma. More stringent molecular selection strategies might produce better outcomes.
dc.description.abstract
This study is funded by Novartis Institutes for Biomedical Research (China). A.B. Lassman was supported in part by grants P30CA013696 and UG1CA189960 from the NCI.
dc.format
application/pdf
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application/pdf
dc.relation
Journal of Neuro-Oncology;146
dc.relation
https://doi.org/10.1007/s11060-019-03337-2
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
dc.subject
Cervell - Càncer - Quimioteràpia
dc.subject
DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neoplasms, Neuroepithelial::Glioma::Astrocytoma::Glioblastoma
dc.subject
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols
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DISEASES::Neoplasms::Neoplastic Processes::Neoplasm Recurrence, Local
dc.subject
ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::neoplasias neuroepiteliales::glioma::astrocitoma::glioblastoma
dc.subject
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada
dc.subject
ENFERMEDADES::neoplasias::procesos neoplásicos::recurrencia neoplásica local
dc.title
A Phase Ib/II, open-label, multicenter study of INC280 (capmatinib) alone and in combination with buparlisib (BKM120) in adult patients with recurrent glioblastoma
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
