Abstract CT131: HPV specific immunotherapy for cervical intraepithelial neoplasia using VGX-3100 induces regression of cervical lesions and potent T-cell responses: Results from a randomized, double-blind, placebo-controlled phase II study
Authors: Morrow Matthew , Trimble Cornelia , Shen Xuefei , Dallas Michael , Weiner David , Boyer Jean , Yan Jian , Kraynyak Kimberly , Sylvester Albert , Giffear Mary , Marcozzi-Pierce Kathleen , Shah Divya , Broderick Kate , Khan Amir , Lee Jessica , Humeau Laurent , Sardesai Niranjan , Bagarazzi Mark 
Published: August 2015

Abstract
The advent of an immunotherapy that imparts a significant impact on the clinical status of advanced cervical intraepithelial neoplasia (CIN) has the potential to provide physicians an important alternative to surgery to treat CIN 2/3 disease. Our previous two phase I studies of VGX-3100, a highly optimized DNA immunotherapy for HPV16/18 delivered using electroporation, drove seroconversion as gauged by ELISA to at least one HPV antigen (E6 or E7) in 100% of patients while 78% of patients mounted a Interferon Gamma (IFNg) ELISpot response. Moreover, all patients showed the presence of CD8 T cells exhibiting full HPV-specific cytolytic functionality, a readout thought to be informative of the ability of VGX-3100 to induce an immune response that may be important for the direct elimination of HPV infected cells.
The phase II study, designated HPV-003, assessed the safety and efficacy of VGX-3100 in 167 women with biopsy-proven CIN 2 or CIN 3 with concurrent HPV16/18 infection. The randomized, placebo-controlled, double-blind study, was stratified by age and severity of CIN and evaluated cervical tissue changes after three 6 mg intramuscular doses of VGX-3100 followed by electroporation (EP) with Inovio's CELLECTRA® 2000 device at weeks 0, 4, and 12. Cervical tissue was examined before starting blinded treatment and 9 months later. The study met its primary efficacy endpoint; the percentage of patients who had regression of CIN 2 or CIN 3 to CIN 1 or no disease at 6 months post third dose was significantly higher in the VGX-3100 group compared to the placebo group (p = 0.017). In addition, the trial demonstrated the ability of VGX-3100 clear HPV infection concurrent with regression of CIN lesions. The study also explored cellular immune responses to VGX-3100 in blood samples taken prior to the first vaccine dose and periodically thereafter. IFN-γ ELISpot results revealed higher responses in the VGX-3100 treated group than in the placebo group, suggesting that VGX-3100 was able to robustly engage the cellular arm of the patients’ immune system.
Altogether, the successful phase 2 results represent a significant milestone in the development of active immunotherapies to treat cancer and infectious diseases and have the potential to provide physicians an important alternative to surgery to treat CIN 2/3 disease. They illustrate the highly promising potential of therapeutic immunization with DNA using electroporation for the treatment of HPV-related precancerous cervical disease in women and present the possibility of treating other HPV-associated cancers.
Citation Format: Matthew Morrow, Cornelia Trimble, Xuefei Shen, Michael Dallas, David Weiner, Jean Boyer, Jian Yan, Kimberly Kraynyak, Albert Sylvester, Mary Giffear, Kathleen Marcozzi-Pierce, Divya Shah, Kate Broderick, Amir Khan, Jessica Lee, Laurent Humeau, Niranjan Sardesai, Mark Bagarazzi. HPV specific immunotherapy for cervical intraepithelial neoplasia using VGX-3100 induces regression of cervical lesions and potent T-cell responses: Results from a randomized, double-blind, placebo-controlled phase II study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT131. doi:10.1158/1538-7445.AM2015-CT131