Durability of response to VGX-3100 treatment of HPV16/18 positive cervical HSIL

Abstract

VGX-3100 is an investigational DNA-based immunotherapy being developed as an alternative to surgery and ablation for cervical High-Grade Squamous Intraepithelial Lesion (HSIL) with the aim of preserving reproductive health while treating precancerous disease. Response durability up to 1.5 y following dosing is now reported. Histologic regression and HPV16 and/or HPV 18 (HPV16/18) clearance were previously demonstrated in a randomized, placebo-controlled, double-blind trial and reported for 6 months after the last dose of VGX-3100 or placebo. The presence of HPV16/18, Pap smear diagnoses, and immunogenicity longer-term responses were assessed at 18 months after the last dose. 91% (32/35) VGX-3100-treated women, whose cervical HSIL regressed and avoided excision at 6 months following study treatment completion, had no detectable HPV16/18 at 18 months following treatment completion. These results were comparable to those for women who received placebo and then later underwent surgery. For VGX-3100 recipients who regressed at 6 months following study treatment completion and avoided excision during the trial, Pap testing showed no HSIL recurrence at 18 months following VGX-3100 treatment. VGX-3100-induced cellular immune responses specific for HPV 16/18 E6/E7 remained higher than for placebo control recipients at 18 months. In women with cervical HSIL who responded to VGX-3100 and were able to avoid surgery, clinical outcomes were comparable to the placebo control group which underwent conventional surgical treatment. These findings extend the understanding of the durability of the treatment effect of VGX-3100 up to 1.5 y and support that VGX-3100 could be used as an alternative to surgery.

Human Papillomavirus Vaccine Efficacy and Effectiveness against Cancer

“…However, there are a few promising therapeutic vaccine candidates, including the HPV type 16 E-7 expressing Lactobacillus-based vaccine for the treatment of HPV-16-vaccine-positive HSIL [111] and the VGX-3100 DNA vaccine with electroporation for patients with cervical intraepithelial neoplasia (CINI) grade 2/3 or 3. The results of the latter study showed regression of the lesions to CINI and clearance of HPV 16/18, helped avoid excision at 6 months following treatment completion, and had no detectable HPV 16/18 at 18 months following treatment completion [112]. There are also a few clinical trials combining therapeutic vaccines with antibodies against programmed death-ligand 1 (PD-L1) and that have been reported to increase immune responses leading to the suppression of tumor growth [113].…”

Enhanced synergistic antitumor effect of a DNA vaccine with anticancer cytokine, MDA-7/IL-24, and immune checkpoint blockade

“…Moreover, there was a significant rise in the population of activated CD8+ T cells and humoral responses among those receiving the vaccine rather than placebo-received ones, suggesting VGX-3100 as a promising DNA vaccine to thoroughly elicit adaptive immunity against HPV-driven cervical cancer [ 19 ]. Additionally, a more recent report has measured the 1.5-year lasting therapeutic effect of VGX-3100 after administration of the final dose and an efficacy index comparable to conventional surgery, introducing vaccination as a promising substitute for radical therapies [ 20 ].…”

Novel Antigenic Targets of HPV Therapeutic Vaccines

“…VGX-3100 showed histological regression in 49.5% (53/107) of treated CIN 2/3 patients compared to 30.6% (11/36) in the placebo group at week 36 in a phase IIb trial [87]. In total, 91% of the women who had experienced regression and avoided excision had no detectable HPV DNA or HSIL recurrence after 18 months [88]. GX-188 showed histological regression in 67% (35/52) of CIN3 patients after 18 months, of which 77% (27/35) cleared their HPV infection (phase II) [89].…”