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Phase II study of MEDI-575, an anti-platelet-derived growth factor-α antibody, in patients with recurrent glioblastoma

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Abstract

MEDI-575, an immunoglobulin G2κ monoclonal antibody, selectively binds to platelet-derived growth factor-α receptor (PDGFR-α) with high specificity. This multicenter, single-arm, open-label, phase II study evaluated the efficacy and safety of MEDI-575 in patients with recurrent glioblastoma. Adults with first recurrence of glioblastoma following surgery, temozolomide, and radiation received MEDI-575 25 mg/kg intravenously over 60 min every 21 days until disease progression or unacceptable toxicity. Six-month progression-free survival rate (PFS-6) was the primary end point; secondary measures included response rate, overall survival (OS), and safety/tolerability. PDGFR-α expression was evaluated by immunohistochemistry. Fifty-six patients were enrolled; median age was 56.5 years (range 23–79), 66 % were male, and 66 % were aged ≥65 years. PFS-6 was 15.4 % [90 % confidence interval (CI) 8.1–24.9]. No complete or partial responses were observed; 23 (41.1 %) patients had stable disease as best response. Median PFS was 1.4 months (90 % CI 1.4, 1.8); median OS was 9.7 months (90 % CI 6.5, 11.8). The most common treatment-related adverse events (AEs) were diarrhea (16 %), nausea (13 %), and fatigue (13 %). Twelve (21 %) patients reported grade ≥3 AEs, with hydrocephalus (n = 3), dysphagia (n = 2), and convulsion (n = 2) reported in more than 1 patient. Two patients had treatment-related Grade ≥3 AEs of decreased lymphocyte count and asthenia (n = 1 each). Seven patients (13 %) discontinued MEDI-575 owing to AEs. Labeling of PDGFRα in glioblastoma cells and tumor-associated stromal cells was highly variable, with no correlation with PFS. MEDI-575, although well tolerated, had limited clinical activity in recurrent glioblastoma.

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Acknowledgments

The authors thank the patients and physicians who participated in this study. They also thank Amy Zannikos, PharmD, of Peloton Advantage for medical writing and editorial support, which were funded by MedImmune.

Funding

This study was sponsored by MedImmune. Medical writing and editorial support were provided by Amy Zannikos, PharmD, at Peloton Advantage and were funded by MedImmune. No author received an honorarium or other form of financial support related to the development of this manuscript.

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Author notes

  1. Surasak Phuphanich

    Present address: Department of Neurology, Division of Neuro-Oncology, Barrow Neurological Institute, 240 West Thomas Road, Suite 400, Phoenix, AZ, 85013, USA

Authors and Affiliations

  1. Johnnie L. Cochran Jr. Brain Tumor Center, Cedars-Sinai Medical Center, 127 South San Vicente Blvd, Los Angeles, CA, USA

    Surasak Phuphanich

  2. Northwestern Brain Tumor Institute, Northwestern University, 675 N. St. Clair, Chicago, IL, 60611, USA

    Jeffrey Raizer

  3. University of Washington, 1959 NE Pacific St., 8th Floor, Seattle, WA, 98195, USA

    Marc Chamberlain

  4. MedImmune, 1 MedImmune Way, Gaithersburg, MD, 20878, USA

    Paola Canelos, Rajesh Narwal, Shengyan Hong, Robert Miday, Minal Nade & Kevin Laubscher

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  1. Surasak Phuphanich
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  2. Jeffrey Raizer
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Corresponding author

Correspondence to Surasak Phuphanich.

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Conflict of interest

S. Phuphanich and M. Chamberlain report no conflicts to disclose. J. Raizer has received research support from MedImmune and has served on an advisory board, without compensation, for MedImmune. P. Canelos, R. Narwal, S. Hong, R. Miday, M. Nade, and K. Laubscher are employees of MedImmune.

Additional information

Jeffrey Raizer and Surasak Phuphanich have contributed equally to this work.

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Phuphanich, S., Raizer, J., Chamberlain, M. et al. Phase II study of MEDI-575, an anti-platelet-derived growth factor-α antibody, in patients with recurrent glioblastoma. J Neurooncol 131, 185–191 (2017). https://doi.org/10.1007/s11060-016-2287-6

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  • DOI: https://doi.org/10.1007/s11060-016-2287-6

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