Skip to main content
Journal cover image

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.

Publication ,  Journal Article
Wick, A; Desjardins, A; Suarez, C; Forsyth, P; Gueorguieva, I; Burkholder, T; Cleverly, AL; Estrem, ST; Wang, S; Lahn, MM; Guba, SC; Capper, D ...
Published in: Invest New Drugs
October 2020

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), median progression-free survival (7.6 vs 11.5 months), and disease control rate (80% [32/40] vs 56% [9/16] patients) respectively. PK profile of galunisertib plus TMZ/RTX regimen was consistent with previously published PK data of galunisertib. The overall safety profile across treatment arms was comparable. Conclusion No differences in efficacy, safety or pharmacokinetic variables were observed between the two treatment arms.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Invest New Drugs

DOI

EISSN

1573-0646

Publication Date

October 2020

Volume

38

Issue

5

Start / End Page

1570 / 1579

Location

United States

Related Subject Headings

  • Temozolomide
  • T-Lymphocyte Subsets
  • Receptor, Transforming Growth Factor-beta Type I
  • Quinolines
  • Pyrazoles
  • Protein Kinase Inhibitors
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wick, A., Desjardins, A., Suarez, C., Forsyth, P., Gueorguieva, I., Burkholder, T., … Rodon, J. (2020). 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. Invest New Drugs, 38(5), 1570–1579. https://doi.org/10.1007/s10637-020-00910-9
Wick, Antje, Annick Desjardins, Cristina Suarez, Peter Forsyth, Ivelina Gueorguieva, Tiana Burkholder, Ann Louise Cleverly, et al. “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.Invest New Drugs 38, no. 5 (October 2020): 1570–79. https://doi.org/10.1007/s10637-020-00910-9.
Wick A, Desjardins A, Suarez C, Forsyth P, Gueorguieva I, Burkholder T, Cleverly AL, Estrem ST, Wang S, Lahn MM, Guba SC, Capper D, Rodon J. 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. Invest New Drugs. 2020 Oct;38(5):1570–1579.
Journal cover image

Published In

Invest New Drugs

DOI

EISSN

1573-0646

Publication Date

October 2020

Volume

38

Issue

5

Start / End Page

1570 / 1579

Location

United States

Related Subject Headings

  • Temozolomide
  • T-Lymphocyte Subsets
  • Receptor, Transforming Growth Factor-beta Type I
  • Quinolines
  • Pyrazoles
  • Protein Kinase Inhibitors
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Humans