Phase 1b/2a study of galunisertib, a small molecule inhibitor of transforming growth factor-beta receptor I, in combination with standard temozolomide-based radiochemotherapy in patients with newly diagnosed malignant glioma.

Investigational New Drugs
Antje WickJordi Rodon

Abstract

Purpose Galunisertib, a TGF-β inhibitor, has demonstrated antitumor effects in preclinical and radiographic responses in some patients with malignant glioma. This Phase 1b/2a trial investigated the clinical benefit of combining galunisertib with temozolomide-based radiochemotherapy (TMZ/RTX) in patients with newly diagnosed malignant glioma (NCT01220271). Methods This is an open-label, 2-arm Phase 1b/2a study (N = 56) of galunisertib (intermittent dosing: 14 days on/14 days off per cycle of 28 days) in combination with TMZ/RTX (n = 40), versus a control arm (TMZ/RTX, n = 16). The primary objective of Phase 1b was to determine the safe and tolerable Phase 2 dose of galunisertib. The primary objective of Phase 2a was to confirm the tolerability and pharmacodynamic profile of galunisertib with TMZ/RTX, and the secondary objectives included determining the efficacy and pharmacokinetic (PK) profile of galunisertib with TMZ/RTX in patients with glioblastoma. This study also characterized the changes in the major T-cell subsets during TMZ/RTX plus galunisertib treatment. Results In the Phase 2a study, efficacy results for patients treated with galunisertib plus TMZ/RTX or TMZ/RTX were: median overall survival (18.2 vs 17.9 months), me...Continue Reading

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Citations

Jan 9, 2021·Signal Transduction and Targeted Therapy·Sijia LiuPeter Ten Dijke
Mar 7, 2021·Cancers·Hong-My NguyenDipongkor Saha
Dec 2, 2020·Pharmacology & Therapeutics·Yi Xiao, Dihua Yu
May 1, 2021·Cancers·Elisabete Cruz Da SilvaLaurence Choulier
Jun 10, 2021·The Oncologist·Lidia GattoAlba Ariela Brandes
Jul 25, 2021·Cancers·Lynn BitarMirko H H Schmidt
Aug 6, 2021·British Journal of Cancer·Samuel S WidodoTheo Mantamadiotis
Sep 28, 2021·The Cancer Journal·Adela Wu, Michael Lim
Sep 21, 2021·Neuro-oncology·Justin V JosephHrvoje Miletic

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Methods Mentioned

BETA
surgical resection
biopsy
enzyme-linked immunosorbent assay
flow cytometry

Clinical Trials Mentioned

NCT01220271

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