THE GLIOBLASTOMA GROUP

Effect of EGFRvIII-targeted vaccine (CDX-110) on immune response and TTP when given with simultaneous standard and continuous temozolomide in patients with GBM.

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Abstract No:

2011

Citation:

J Clin Oncol 26: 2008 (May 20 suppl; abstr 2011)

Author(s):

J. H. Sampson, G. E. Archer, D. D. Bigner, T. Davis, H. S. Friedman, T. Keler, D. A. Mitchell, D. A. Reardon, R. Sawaya, A. B. Heimberger

Abstract:

Background: Conventional therapies for GBM fail to target tumor cells exclusively. Immunologic targeting of tumor- specific gene mutations may allow more precise eradication of neoplastic cells. The epidermal growth factor receptor variant III (EGFRvIII) is a consistent and immunogenic mutation that is not expressed in any normal tissues, but is widely expressed in GBMs and other neoplasms making it an attractive target for active immunotherapy. Methods: A phase II multicenter clinical trial was undertaken to assess the immunogenicity and efficacy of an EGFRvIII-specific peptide vaccine in patients with newly-diagnosed, EGFRvIII+ GBM in combination with simultaneous standard or continuous temozolomide (TMZ). After resection and radiation/TMZ (75 mg/m²/d), consecutive cohorts received subsequent monthly cycles of 200 mg/m² (N=13) or continuous 100 mg/m² (N=8) TMZ simultaneous with intradermal vaccinations with an EGFRvIII-specific peptide (PEPvIII) conjugated to keyhole limpet hemocyanin (KLH) until tumor progression or death. Results: 21 patients were enrolled. There was one allergic reaction, but no other SAEs. There were no significant differences in vaccine immunogenicity (p>0.999; binomial proportions), PFS (p=0.7979; log-rank), or OS (p=0.7728; log-rank) between TMZ regimens. Although TMZ induced grade II lymphopenia in 53.8% of patients, the co-administration of TMZ with the EGFRvIII vaccine (CDX-110) results in strong sustained immune responses to EGFRvIII in 100% (95%CI: 0.72, 1.00) of evaluated patients. Median PFS was 16.6 months (95%CI: 9.1, 22.7). Median survival has not been reached. The survival of the vaccinated patients is better than a matched historical control group (14.3 months; 95%CI: 13.0, 16.2) (p<0.0001; log-rank) and a subgroup treated with TMZ (15.2; 95%CI: 13.9, 20.5) (p=0.0078) and is also equivalent to the results seen in patients vaccinated without simultaneous temozolomide (p=0.4108; log-rank). Conclusions: CDX-110 peptide vaccination with standard of care temozolomide in patients with GBM appears very promising and is under investigation in a phase III, randomized clinical trial.