ITOC2 – 020. VGX-3100 Immunotherapy for CIN2/3 Induces regression of cervical lesions and viral clearance (Phase II study): Implications for treatment of HPV associated cancers

Immunotherapy that significantly impacts 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 VGX3100, a highly optimised DNA immunotherapy for HPV16/18, drove seroconversion to HPV antigens in 100% of patients while 78% of patients mounted an Interferon Gamma (IFNg) ELISpot response. Flow analysis revealed IFNg production from both CD4+ and CD8+ T cells, as well as the induction of patient CD8s with antigen specific CTL activity. This randomized, placebo-controlled, double-blind Phase II study assessed the safety and efficacy of VGX3100 in 167 women with biopsy-proven CIN 2/3 with concurrent HPV16 or 18 infection. The study evaluated cervical tissue changes after three 6 mg intramuscular doses of VGX-3100 with Inovio’s CELLECTRA® 2000 electroporation device at weeks 0, 4, 12. Cervical tissue was examined before starting blinded treatment and 9 months later. The study met its primary efficacy endpoint; Significantly higher percentage of VGX3100 treated patients versus placebo showed regression of CIN 2/3 to CIN 1 or no disease (p = 0.017). In addition, VGX3100 recipients demonstrated significantly stronger post-vaccination IFNg ELISpot responses and cleared HPV infection concurrent with regression of CIN lesions. The efficacy data with VGX3100 support the exciting possibility of treating HPV-associated cancers. Immunotherapy that significantly impacts 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 VGX3100, a highly optimised DNA immunotherapy for HPV16/18, drove seroconversion to HPV antigens in 100% of patients while 78% of patients mounted an Interferon Gamma (IFNg) ELISpot response. Flow analysis revealed IFNg production from both CD4+ and CD8+ T cells, as well as the induction of patient CD8s with antigen specific CTL activity. This randomized, placebo-controlled, double-blind Phase II study assessed the safety and efficacy of VGX3100 in 167 women with biopsy-proven CIN 2/3 with concurrent HPV16 or 18 infection. The study evaluated cervical tissue changes after three 6 mg intramuscular doses of VGX-3100 with Inovio’s CELLECTRA® 2000 electroporation device at weeks 0, 4, 12. Cervical tissue was examined before starting blinded treatment and 9 months later. The study met its primary efficacy endpoint; Significantly higher percentage of VGX3100 treated patients versus placebo showed regression of CIN 2/3 to CIN 1 or no disease (p = 0.017). In addition, VGX3100 recipients demonstrated significantly stronger post-vaccination IFNg ELISpot responses and cleared HPV infection concurrent with regression of CIN lesions. The efficacy data with VGX3100 support the exciting possibility of treating HPV-associated cancers.