Abstracts of the 29th Annual Scientific Meeting of the Society for Immunotherapy of Cancer (SITC)
- Oral presentation
- Open Access
DNA vaccine VGX-3100 with electroporation induces regression of cervical intraepithelial neoplasia 2/3 and clears HPV infection with robust T cell responses: results of a randomized, double-blind, placebo-controlled Phase II trial
Journal for ImmunoTherapy of Cancer volume 2, Article number: O17 (2014)
The Phase II study, designated HPV-003 (NCT01304524), assessed the safety and efficacy of VGX-3100 in 167 women with biopsy-proven cervical intraepithelial neoplasia (CIN) 2 or CIN 3 and HPV-16 or -18. 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 the DNA vaccine 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 primary endpoint was regression of CIN 2 or CIN 3 to CIN 1 or no disease at 6 months post third dose. In the per-protocol population (PPP), lesions regressed in 53 of the 107 women receiving VGX-3100 (49.5%) as compared to 11 of the 36 women in the placebo group (p < 0.025). The secondary endpoint was to demonstrate HPV-16 or -18 clearance from the cervix in conjunction with regression of CIN 2/3 to CIN1 or no disease. Among the 107 women in the VGX-3100 group, 43 demonstrated regression and virological clearance (40.2%), compared to 5 out of 35 (14.3%) in the placebo group (p < 0.025).
The study also explored cell mediated 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. Flow cytometry and immunohistochemistry analyses are also ongoing. Finally, subjects were also monitored for tolerability and safety. The treatment was generally well-tolerated, with only administration site redness occurring significantly more frequently in the VGX-3100 group compared to the placebo group in the 7- and 28-day periods following treatment.
Altogether, the successful Phase II results clearly illustrate the highly promising potential of therapeutic vaccination with DNA followed by electroporation for the treatment of HPV-related precancerous cervical disease in women as well as HPV-associated cervical, head and neck, and anogenital cancers.
Rights and permissions
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
About this article
Cite this article
Humeau, L., Trimble, C., Morrow, M. et al. DNA vaccine VGX-3100 with electroporation induces regression of cervical intraepithelial neoplasia 2/3 and clears HPV infection with robust T cell responses: results of a randomized, double-blind, placebo-controlled Phase II trial. j. immunotherapy cancer 2 (Suppl 3), O17 (2014). https://doi.org/10.1186/2051-1426-2-S3-O17
- Placebo Group
- Cervical Intraepithelial Neoplasia
- Cell Mediate Immune Response
- Vaccine Dose
- Successful Phase