Phase II study of ERC1671 plus bevacizumab versus bevacizumab plus placebo in recurrent glioblastoma: interim results and correlations with CD4+ T-lymphocyte counts

Daniela A Bota; Jinah Chung; Manisha Dandekar; Jose A Carrillo; Xiao-Tang Kong; Beverly D Fu; Frank Pk Hsu; Axel H Schönthal; Florence M Hofman; Thomas C Chen; Raphael Zidovetzki; Chrystel Pretto; Ankie Strik; Virgil Ejc Schijns; Apostolos Stathopoulos

doi:10.2217/cns-2018-0009

Phase II study of ERC1671 plus bevacizumab versus bevacizumab plus placebo in recurrent glioblastoma: interim results and correlations with CD4⁺ T-lymphocyte counts

CNS Oncol. 2018 Jul 1;7(3):CNS22. doi: 10.2217/cns-2018-0009. Epub 2018 Aug 29.

Authors

Daniela A Bota^{1

2

3}, Jinah Chung³, Manisha Dandekar³, Jose A Carrillo^{1

2

3}, Xiao-Tang Kong^{1

2

3}, Beverly D Fu^{1

3}, Frank Pk Hsu^{2

3}, Axel H Schönthal⁴, Florence M Hofman⁵, Thomas C Chen⁶, Raphael Zidovetzki⁷, Chrystel Pretto⁸, Ankie Strik^{6

8}, Virgil Ejc Schijns^{8

9}, Apostolos Stathopoulos^{8

9

10}

Affiliations

¹ Department of Neurology, University of California Irvine, Irvine, CA 92868, USA.
² Department of Neurological Surgery, University of California Irvine, Irvine, CA 92868, USA.
³ Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA 92868, USA.
⁴ Department of Molecular Microbiology & Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
⁵ Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
⁶ Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
⁷ Cell Biology & Neuroscience, University of California, Riverside, CA 92507, USA.
⁸ Epitopoietic Research Corporation, Gembloux, 5032 Isnes, Belgium.
⁹ Cell Biology & Immunology Group, Wageningen University, 6708 Wageningen, The Netherlands.
¹⁰ Department of Neurosurgery, Euroclinics Hospital, 151 21 Athens, Greece.

Abstract

Aim: ERC1671 is an allogeneic/autologous therapeutic glioblastoma (GBM) vaccine - composed of whole, inactivated tumor cells mixed with tumor cell lysates derived from the patient and three GBM donors.

Methods: In this double-blinded, randomized, Phase II study bevacizumab-naive patients with recurrent GBM were randomized to receive either ERC1671 in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) (Leukine^® or sargramostim) and cyclophosphamide plus bevacizumab, or placebo plus bevacizumab. Interim results: Median overall survival (OS) of patients treated with ERC1671 plus bevacizumab was 12 months. In the placebo plus bevacizumab group, median OS was 7.5 months. The maximal CD4⁺ T-lymphocyte count correlated with OS in the ERC1671 but not in the placebo group.

Conclusion: The addition of ERC1671/GM-CSF/cyclophosphamide to bevacizumab resulted in a clinically meaningful survival benefit with minimal additional toxicity.

Keywords: CD4+ T lymphocyte; ERC1671; GBM; GBM vaccine; allogeneic; autologous; bevacizumab; glioma surgery; immunotherapy.

Publication types

Clinical Trial, Phase II
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Antineoplastic Agents, Immunological / therapeutic use*
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Bevacizumab / therapeutic use*
Brain Neoplasms / drug therapy*
Brain Neoplasms / pathology
CD4-Positive T-Lymphocytes / pathology*
Cyclophosphamide / therapeutic use
Double-Blind Method
Female
Glioblastoma / drug therapy*
Glioblastoma / pathology
Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use
Humans
Immunomodulation*
Kaplan-Meier Estimate
Male
Middle Aged
Neoplasm Recurrence, Local
Treatment Outcome

Substances

Antineoplastic Agents, Immunological
Bevacizumab
Granulocyte-Macrophage Colony-Stimulating Factor
Cyclophosphamide

Grants and funding

P30 CA062203/CA/NCI NIH HHS/United States