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Open Access 01-01-2020 | Glioblastoma | Clinical Study

A Phase Ib/II, open-label, multicenter study of INC280 (capmatinib) alone and in combination with buparlisib (BKM120) in adult patients with recurrent glioblastoma

Authors: Martin van den Bent, Analia Azaro, Filip De Vos, Juan Sepulveda, W. K. Alfred Yung, Patrick Y. Wen, Andrew B. Lassman, Markus Joerger, Ghazaleh Tabatabai, Jordi Rodon, Ralph Tiedt, Sylvia Zhao, Tiina Kirsilae, Yi Cheng, Sergio Vicente, O. Alejandro Balbin, Hefei Zhang, Wolfgang Wick

Published in: Journal of Neuro-Oncology | Issue 1/2020

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.

Trial registration: NCT01870726.

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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
Authors: Martin van den Bent
Analia Azaro
Filip De Vos
Juan Sepulveda
W. K. Alfred Yung
Patrick Y. Wen
Andrew B. Lassman
Markus Joerger
Ghazaleh Tabatabai
Jordi Rodon
Ralph Tiedt
Sylvia Zhao
Tiina Kirsilae
Yi Cheng
Sergio Vicente
O. Alejandro Balbin
Hefei Zhang
Wolfgang Wick
Publication date: 01-01-2020
Publisher: Springer US
Keywords: Glioblastoma
Fluorescence in Situ Hybridization
Glioblastoma
Glioblastoma
Published in: Journal of Neuro-Oncology / Issue 1/2020
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-019-03337-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

A Phase Ib/II, open-label, multicenter study of INC280 (capmatinib) alone and in combination with buparlisib (BKM120) in adult patients with recurrent glioblastoma

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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