A phase II study evaluating the efficacy and safety of AMG 102 (rilotumumab) in patients with recurrent glioblastoma

Patrick Y. Wen, David Schiff, Timothy F. Cloughesy, Jeffrey J. Raizer, John J Laterra, Melanie Smitt, Michael Wolf, Kelly S. Oliner, Abraham Anderson, Min Zhu, Elwyn Loh, David A. Reardon

Research output: Contribution to journalArticle

Abstract

This phase II study evaluated the efficacy and safety of AMG 102 (rilotumumab), a fully human monoclonal antibody against hepatocyte growth factor/scatter factor (HGF/SF), in patients with recurrent glioblastoma (GBM). Patients with histologically confirmed, measurable recurrent GBM or gliosarcoma (World Health Organization grade 4) and ≤3 relapses or prior systemic therapies received AMG 102 (10 or 20 mg/kg) by infusion every 2 weeks. The primary endpoint was best confirmed objective response rate (central assessment) per Macdonald criteria. Of the 61 patients who enrolled, 60 received AMG 102. Twenty-nine patients (48%) had previously received bevacizumab. There were no objective responses per central assessment, but 1 patient had an objective response per investigator assessment. Median overall survival (95% CI) in the 10- and 20-mg/kg cohorts was 6.5 months (4.1-9.8) and 5.4 months (3.4-11.4), respectively, and progression-free survival (PFS) per central assessment was 4.1 weeks (4.0-4.1) and 4.3 weeks (4.1-8.1), respectively. PFS was similar among patients who had previously received bevacizumab compared with bevacizumab-naive patients. The most common adverse events were fatigue (38%), headache (33%), and peripheral edema (23%). AMG 102 serum concentrations increased approximately dose-proportionally with 2-fold accumulation at steady state. Plasma total HGF/SF and soluble c-Met concentrations increased 12.05- and 1.12-fold, respectively, from baseline during AMG 102 treatment. AMG 102 monotherapy at doses up to 20 mg/kg was not associated with significant antitumor activity in heavily pretreated patients with recurrent GBM.

Original languageEnglish (US)
Pages (from-to)437-446
Number of pages10
JournalNeuro-Oncology
Volume13
Issue number4
DOIs
StatePublished - Apr 2011

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Glioblastoma
Safety
Hepatocyte Growth Factor
Disease-Free Survival
Gliosarcoma
rilotumumab
Fatigue
Headache
Edema
Monoclonal Antibodies
Research Personnel
Recurrence
Survival
Therapeutics
Serum
Bevacizumab

Keywords

  • AMG 102
  • C-Met
  • Glioblastoma
  • Hepatocyte growth factor
  • Phase II clinical trial.
  • Rilotumumab

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Clinical Neurology

Cite this

A phase II study evaluating the efficacy and safety of AMG 102 (rilotumumab) in patients with recurrent glioblastoma. / Wen, Patrick Y.; Schiff, David; Cloughesy, Timothy F.; Raizer, Jeffrey J.; Laterra, John J; Smitt, Melanie; Wolf, Michael; Oliner, Kelly S.; Anderson, Abraham; Zhu, Min; Loh, Elwyn; Reardon, David A.

In: Neuro-Oncology, Vol. 13, No. 4, 04.2011, p. 437-446.

Research output: Contribution to journalArticle

Wen, PY, Schiff, D, Cloughesy, TF, Raizer, JJ, Laterra, JJ, Smitt, M, Wolf, M, Oliner, KS, Anderson, A, Zhu, M, Loh, E & Reardon, DA 2011, 'A phase II study evaluating the efficacy and safety of AMG 102 (rilotumumab) in patients with recurrent glioblastoma', Neuro-Oncology, vol. 13, no. 4, pp. 437-446. https://doi.org/10.1093/neuonc/noq198
Wen, Patrick Y. ; Schiff, David ; Cloughesy, Timothy F. ; Raizer, Jeffrey J. ; Laterra, John J ; Smitt, Melanie ; Wolf, Michael ; Oliner, Kelly S. ; Anderson, Abraham ; Zhu, Min ; Loh, Elwyn ; Reardon, David A. / A phase II study evaluating the efficacy and safety of AMG 102 (rilotumumab) in patients with recurrent glioblastoma. In: Neuro-Oncology. 2011 ; Vol. 13, No. 4. pp. 437-446.
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