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.
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Authors | Patrick Y Wen, David Schiff, Timothy F Cloughesy, Jeffrey J Raizer, John Laterra, Melanie Smitt, Michael Wolf, Kelly S Oliner, Abraham Anderson, Min Zhu, Elwyn Loh, David A Reardon |
Journal | Neuro-oncology
(Neuro Oncol)
Vol. 13
Issue 4
Pg. 437-46
(Apr 2011)
ISSN: 1523-5866 [Electronic] England |
PMID | 21297127
(Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Biomarkers, Tumor
- rilotumumab
- Hepatocyte Growth Factor
- Proto-Oncogene Proteins c-met
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Topics |
- Adult
- Aged
- Antibodies, Monoclonal
(pharmacokinetics, therapeutic use)
- Antibodies, Monoclonal, Humanized
- Biomarkers, Tumor
(blood)
- Brain Neoplasms
(blood, drug therapy)
- Female
- Glioblastoma
(blood, drug therapy)
- Hepatocyte Growth Factor
(blood)
- Humans
- Male
- Middle Aged
- Neoplasm Recurrence, Local
(blood, drug therapy)
- Proto-Oncogene Proteins c-met
(blood)
- Survival Rate
- Tissue Distribution
- Treatment Outcome
- Young Adult
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