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

Phuphanich, Surasak; Raizer, Jeffrey J.; Chamberlain, Marc C.; Canelos, Paola; Narwal, Rajesh; Hong, Shengyan; Miday, Robert; Nade, Minal; Laubscher, Kevin

doi:10.1007/s11060-016-2287-6

Cited by 18 publications

(12 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, recent clinical trials showed that dasatinib in conjunction with bevacizumab did not appear to benefit patients with newly diagnosed and recurrent GBM (94,95). MEDI-575, an immunoglobulin G2k monoclonal antibody that selectively binds to platelet-derived growth factor receptor a (PDGFRa), also showed limited clinical efficacy in recurrent GBM in a Phase II clinical trial (96).…”

Section: Pdgfr and Src Family Kinases (Sfks) And Their Inhibitorsmentioning

confidence: 99%

Visualization of Diagnostic and Therapeutic Targets in Glioma With Molecular Imaging

Iagaru

et al. 2020

Front. Immunol.

View full text Add to dashboard Cite

Gliomas, particularly high-grade gliomas including glioblastoma (GBM), represent the most common and malignant types of primary brain cancer in adults, and carry a poor prognosis. GBM has been classified into distinct subgroups over the years based on cellular morphology, clinical characteristics, biomarkers, and neuroimaging findings. Based on these classifications, differences in therapeutic response and patient outcomes have been established. Recently, the identification of complex molecular signatures of GBM has led to the development of diverse targeted therapeutic regimens and translation into multiple clinical trials. Chemical-, peptide-, antibody-, and nanoparticle-based probes have been designed to target specific molecules in gliomas and then be visualized with multimodality molecular imaging (MI) techniques including positron emission tomography (PET), single-photon emission computed tomography (SPECT), near-infrared fluorescence (NIRF), bioluminescence imaging (BLI), and magnetic resonance imaging (MRI). Thus, multiple molecules of interest can now be noninvasively imaged to guide targeted therapies with a potential survival benefit. Here, we review developments in molecular-targeted diagnosis and therapy in glioma, MI of these targets, and MI monitoring of treatment response, with a focus on the biological mechanisms of these advanced molecular probes. MI probes have the potential to noninvasively demonstrate the pathophysiologic features of glioma for diagnostic, treatment, and response assessment considerations for various targeted therapies, including immunotherapy. However, most MI tracers are in preclinical development, with only integrin a V b 3 and isocitrate dehydrogenase (IDH)-mutant MI tracers having been translated to patients. Expanded international collaborations would accelerate translational research in the field of glioma MI.

show abstract

Section: Pdgfr and Src Family Kinases (Sfks) And Their Inhibitorsmentioning

confidence: 99%

Visualization of Diagnostic and Therapeutic Targets in Glioma With Molecular Imaging

Iagaru

et al. 2020

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…In mice bearing GL261 or U87 tumors, MEDI1317 was shown to increase mouse survival only when it was combined with cediranib (Peterson et al, 2015 ). In a phase II clinical study involving 56 patients with recurrent GBM, the administration of MEDI-575 was shown to be well tolerated but did not result in any significant clinical activity (Phuphanich et al, 2017 ).…”

Section: The Different Gbm Treatments Commercialized or Under Developmentioning

confidence: 99%

Glioblastoma Treatments: An Account of Recent Industrial Developments

Alphandéry

2018

Front. Pharmacol.

View full text Add to dashboard Cite

The different drugs and medical devices, which are commercialized or under industrial development for glioblastoma treatment, are reviewed. Their different modes of action are analyzed with a distinction being made between the effects of radiation, the targeting of specific parts of glioma cells, and immunotherapy. Most of them are still at a too early stage of development to firmly conclude about their efficacy. Optune, which triggers antitumor activity by blocking the mitosis of glioma cells under the application of an alternating electric field, seems to be the only recently developed therapy with some efficacy reported on a large number of GBM patients. The need for early GBM diagnosis is emphasized since it could enable the treatment of GBM tumors of small sizes, possibly easier to eradicate than larger tumors. Ways to improve clinical protocols by strengthening preclinical studies using of a broader range of different animal and tumor models are also underlined. Issues related with efficient drug delivery and crossing of blood brain barrier are discussed. Finally societal and economic aspects are described with a presentation of the orphan drug status that can accelerate the development of GBM therapies, patents protecting various GBM treatments, the different actors tackling GBM disease, the cost of GBM treatments, GBM market figures, and a financial analysis of the different companies involved in the development of GBM therapies.

show abstract

“…MEDI-3617 and MEDI-575 are two anti-platelet-derived growth factor receptor α (PDGFRA) antibodies that were developed for GBM therapy (38,136). However, a phase II clinical study showed that although MEDI-575 was well-tolerated, it did not exhibit any significant clinical activity (136).…”

Section: Pharmaceutical Products Tested In Clinical Trialsmentioning

confidence: 99%

Glioblastoma pharmacotherapy: A multifaceted perspective of conventional and emerging treatments (Review)

et al. 2021

View full text Add to dashboard Cite

Due to its localisation, rapid onset, high relapse rate and resistance to most currently available treatment methods, glioblastoma multiforme (GBM) is considered to be the deadliest type of all gliomas. Although surgical resection, chemotherapy and radiotherapy are among the therapeutic strategies used for the treatment of GBM, the survival rates achieved are not satisfactory, and there is an urgent need for novel effective therapeutic options. In addition to single-target therapy, multi-target therapies are currently under development. Furthermore, drugs are being optimised to improve their ability to cross the blood-brain barrier. In the present review, the main strategies applied for GBM treatment in terms of the most recent therapeutic agents and approaches that are currently under pre-clinical and clinical testing were discussed. In addition, the most recently reported experimental data following the testing of novel therapies, including stem cell therapy, immunotherapy, gene therapy, genomic correction and precision medicine, were reviewed, and their advantages and drawbacks were also summarised.

show abstract

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

Cited by 18 publications

References 19 publications

Visualization of Diagnostic and Therapeutic Targets in Glioma With Molecular Imaging

Visualization of Diagnostic and Therapeutic Targets in Glioma With Molecular Imaging

Glioblastoma Treatments: An Account of Recent Industrial Developments

Glioblastoma pharmacotherapy: A multifaceted perspective of conventional and emerging treatments (Review)

Contact Info

Product

Resources

About