title: A phase II study evaluating the efficacy and safety of AMG 102 (rilotumumab) in patients with recurrent glioblastoma.
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.
authors.affiliation: Center for Neuro-Oncology, Dana Farber/Brigham and Women's Cancer Center, Shields Warren 430 D, Boston, MA 02115, USA. patrick_wen@dfci.harvard.edu
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Wen
authors.forename: David
authors.initials: D
authors.lastname: Schiff
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Cloughesy
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Raizer
authors.forename: John
authors.initials: J
authors.lastname: Laterra
authors.forename: Melanie
authors.initials: M
authors.lastname: Smitt
authors.forename: Michael
authors.initials: M
authors.lastname: Wolf
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Oliner
authors.forename: Abraham
authors.initials: A
authors.lastname: Anderson
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
authors.forename: Elwyn
authors.initials: E
authors.lastname: Loh
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor / Q000097:blood*; D001932:Brain Neoplasms / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005909:Glioblastoma / Q000097:blood / Q000188:drug therapy*; D017228:Hepatocyte Growth Factor / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000188:drug therapy*; D019859:Proto-Oncogene Proteins c-met / Q000097:blood; D015996:Survival Rate; D014018:Tissue Distribution; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; C524459:rilotumumab; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met