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Epidermal growth factor receptor variant III (EGFRvIII) vaccine (CDX-110) in GBM.

Publication ,  Journal Article
Heimberger, AB; Archer, GE; Mitchell, DA; Bigner, DD; Schmittling, RJ; Herndon, JE; Davis, T; Friedman, HS; Keler, T; Reardon, DA; Sampson, JH
Published in: J Clin Oncol
May 20, 2009

2021 Background: Unlike conventional therapies for GBM, immunologic targeting of tumor-specific gene mutations allows precise eradication of neoplastic cells with reduced toxicity. EGFRvIII is a constitutively activated and immunogenic mutation not expressed in normal tissues, but widely expressed in GBM and other neoplasms. The cancer vaccine CDX-110 is comprised of an EGFRvIII-specific peptide sequence linked to keyhole limpet hemocyanin (KLH). METHODS: A phase II multi-center trial assessed the immunogenicity and efficacy of CDX-110 in patients with newly-diagnosed, EGFRvIII+ GBM. After resection and radiation / TMZ, patients received CDX-110 vaccinations biweekly x 3, then monthly until tumor progression. Sequential cohorts received CDX-110 alone [ACTIVATE (n = 18)] or in combination with TMZ (200 mg/m(2) x 5/28 days [ACT II A (n = 13)]) or (100 mg/m(2) x 21/28 days [ACT II B (n=10)]). RESULTS: Reversible systemic drug hypersensitivity reactions were seen in 1 ACTIVATE and 4 ACT II patients. Two patients had non-specific changes on MRI which were possibly due to the vaccine but which resolved. Despite grade 2 or 3 lymphopenia in all ACT II patients, EGFRvIII-specific immune responses were generated in all patients, and all immune responses were sustained or enhanced during subsequent TMZ cycles. Although ACT II B patients had more severe TMZ-induced lymphopenia, they developed greater EGFRvIII-specific immune responses (p = 0.028) when compared to ACT II A. EGFRvIII-specific IgG1 also increased in avidity with vaccination (Ka>2x10(9)M(-1)) in a randomly selected subset of 4 patients (p = 0.000068). Of the 23 recurrent tumors studied, 18 lost EGFRvIII expression (p = 0.001). There are no significant differences between ACT II A and B in estimated median TTP (18.5 vs. 14.9 months, p = 0.31) and OS (23.6 vs. 19.9 months, p = 0.75). ACTIVATE TTP (14.2 months) and OS (26.0 months) and ACT II TTP (15.2 months) and OS (23.6 months) compare favorably to a TMZ-treated, matched historical control group (TTP: 6.3 months; OS: 15.0 months). CONCLUSIONS: CDX-110 vaccination in patients with GBM appears very promising. TMZ enhances immune responses despite lymphodepletion. CDX-110 with simultaneous TMZ is under further investigation in a larger phase II trial. [Table: see text].

Duke Scholars

Published In

J Clin Oncol

EISSN

1527-7755

Publication Date

May 20, 2009

Volume

27

Issue

15_suppl

Start / End Page

2021

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

APA
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MLA
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Heimberger, A. B., Archer, G. E., Mitchell, D. A., Bigner, D. D., Schmittling, R. J., Herndon, J. E., … Sampson, J. H. (2009). Epidermal growth factor receptor variant III (EGFRvIII) vaccine (CDX-110) in GBM. J Clin Oncol, 27(15_suppl), 2021.
Heimberger, A. B., G. E. Archer, D. A. Mitchell, D. D. Bigner, R. J. Schmittling, J. E. Herndon, T. Davis, et al. “Epidermal growth factor receptor variant III (EGFRvIII) vaccine (CDX-110) in GBM.J Clin Oncol 27, no. 15_suppl (May 20, 2009): 2021.
Heimberger AB, Archer GE, Mitchell DA, Bigner DD, Schmittling RJ, Herndon JE, et al. Epidermal growth factor receptor variant III (EGFRvIII) vaccine (CDX-110) in GBM. J Clin Oncol. 2009 May 20;27(15_suppl):2021.
Heimberger, A. B., et al. “Epidermal growth factor receptor variant III (EGFRvIII) vaccine (CDX-110) in GBM.J Clin Oncol, vol. 27, no. 15_suppl, May 2009, p. 2021.
Heimberger AB, Archer GE, Mitchell DA, Bigner DD, Schmittling RJ, Herndon JE, Davis T, Friedman HS, Keler T, Reardon DA, Sampson JH. Epidermal growth factor receptor variant III (EGFRvIII) vaccine (CDX-110) in GBM. J Clin Oncol. 2009 May 20;27(15_suppl):2021.

Published In

J Clin Oncol

EISSN

1527-7755

Publication Date

May 20, 2009

Volume

27

Issue

15_suppl

Start / End Page

2021

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences