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Ref Type Journal Article
PMID (31776899)
Authors van den Bent M, Azaro A, De Vos F, Sepulveda J, Yung WKA, Wen PY, Lassman AB, Joerger M, Tabatabai G, Rodon J, Tiedt R, Zhao S, Kirsilae T, Cheng Y, Vicente S, Balbin OA, Zhang H, Wick W
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.
Journal Journal of neuro-oncology
Vol 146
Issue 1
Date 2020 Jan
URL
Abstract Text 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.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.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%).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.NCT01870726.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
PTEN negative glioblastoma no benefit Buparlisib + Capmatinib Phase Ib/II Actionable In a Phase Ib/II trial, combination of Buparlisib (BKM120) and Tabrecta (capmatinib) did not reach target exposure due to potential drug-drug interaction, and demonstrated minimal activity in patients with glioblastoma harboring PTEN alterations including deletion, mutation, or negative protein expression, therefore, Phase II of the trial was not initiated (PMID: 31776899; NCT01870726). 31776899
PTEN mutant glioblastoma no benefit Buparlisib + Capmatinib Phase Ib/II Actionable In a Phase Ib/II trial, combination of Buparlisib (BKM120) and Tabrecta (capmatinib) did not reach target exposure due to potential drug-drug interaction, and demonstrated minimal activity in patients with glioblastoma harboring PTEN alterations including deletion, mutation, or negative protein expression, therefore, Phase II of the trial was not initiated (PMID: 31776899; NCT01870726). 31776899
PTEN del glioblastoma no benefit Buparlisib + Capmatinib Phase Ib/II Actionable In a Phase Ib/II trial, combination of Buparlisib (BKM120) and Tabrecta (capmatinib) did not reach target exposure due to potential drug-drug interaction, and demonstrated minimal activity in patients with glioblastoma harboring PTEN alterations including deletion, mutation, or negative protein expression, therefore, Phase II of the trial was not initiated (PMID: 31776899; NCT01870726). 31776899