Work

1184 VGX-3100 DNA immunotherapy for HPV-16/18–associated cervical high-grade squamous intraepithelial lesions: a phase III randomized trial

Year: 2026

Type: conference-abstract

Abstract: Background Persistent infection with human papillomavirus (HPV) type 16 or 18 is an important cause of cervical high-grade squamous intraepithelial lesions (HSILs). Standard excisional treatment removes the cervical lesion but does not directly target the underlying HPV infection and may adversely affect subsequent reproductive outcomes. VGX-3100 is a DNA immunotherapy targeting HPV-16/18 E6 and E7 that is designed to induce antigen-specific T-cell immunity and thereby promote viral clearance and lesion regression. We evaluated the efficacy and safety of VGX-3100 in women with HPV-16/18–associated cervical HSIL.Methods In this multicenter, randomized, double-blind, placebo-controlled phase III trial conducted at 22 sites in China, women 18 years of age or older with histologically confirmed cervical HSIL (CIN2 or CIN3) associated with HPV-16/18 were randomly assigned in a 2:1 ratio to receive VGX-3100 (6 mg) or placebo at Day 1, Week 4, and Week 12 by intramuscular injection followed by CELLECTRA adaptive electroporation. Randomization was stratified by CIN grade, age, and body-mass index. The primary endpoint was histologic regression of cervical HSIL accompanied by HPV-16/18 clearance at week 36. Secondary endpoints included safety, histologic regression, HPV-16/18 clearance and immunogenicity.Results Overall, 207 participants were randomized to VGX-3100 (n=139) or placebo (n=68). In the prespecified primary analysis of the mITT population at week 36, the primary endpoint was achieved by 73/139 (52.5%) participants receiving VGX-3100 versus 24/68 (35.3%) receiving placebo (risk difference, 17.2 percentage points; 95% CI, 2.7–30.6; P=0.025). HPV-16/18 clearance occurred in 55.4% versus 38.2%, respectively (risk difference, 17.2 percentage points; 95% CI, 2.6–30.8). Histologic outcomes generally favored VGX-3100, with greater regression and less residual high-grade disease than with placebo. Treatment-emergent adverse events occurred in 94.2% and 94.1% of participants, respectively, with injection-site pain being the most common event in both groups. Serious adverse events occurred in 3.6% and 2.9%, respectively; none were treatment-related. Immunogenicity analyses showed greater HPV-16/18-specific IFN-γ-secreting T cell and antibody responses with VGX-3100 than placebo; flow-cytometric analyses showed heterogeneous changes from baseline across CD8 + T-cell phenotypes.Conclusions VGX-3100 significantly increased combined histologic regression and HPV-16/18 clearance versus placebo in women with HPV-16/18-associated cervical HSIL, with no treatment-related serious adverse events. This is the first reported positive phase III trial of a therapeutic HPV vaccine, supporting antigen-specific DNA immunotherapy as a potential non-surgical therapeutic approach for HPV-16/18-associated cervical HSIL. (Funded by ApolloBio; trial registration numbers, CTR20201547 and ChiCTR2300071848.)Acknowledgements We thank the patients who participated in the trial and their families, as well as the staff at the participating sites, for their time, support, and commitment to the trial. We also thank Ruichen Wang, Yunpeng Sun, and Qiao Liu for project management; Weiwei Wang, Chun Liu, and Juan Zhu for medical monitoring; Hongchao Ren for technical support of delivery device; Peihu Fan and Hanqiao Yu for immunological data analysis; the members of the Data and Safety Monitoring Board and the Pathological Adjudication Committee; the HPV-303CHN Study Team and other members of the VGX-3100 project team from ApolloBio and Inovio for their contributions to the study; Tigermed, the contract research organization for the trial, for operational support; and Teddy Clinical Research Laboratory for serving as the central laboratory for HPV testing, histopathologic assessment, and immunogenicity testing.Trial Registration The trial was registered with the Center for Drug Evaluation (CDE), National Medical Products Administration (NMPA), China (registration no. CTR20201547; first posted July 29, 2020), before enrollment of the first participant, and with the Chinese Clinical Trial Registry (ChiCTR2300071848; retrospectively registered on May 26, 2023).Ethics Approval This trial was approved by the Ethics Committee of the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (Approval No. 20/152-2348; initial approval on 22 June 2020; latest protocol amendment, version 5.1, approved on 15 April 2025), and by the ethics committees or institutional review boards of all 22 participating sites. The trial was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. All participants provided written informed consent before undergoing any study-related procedures.

Source: Journal for ImmunoTherapy of Cancer

DOI: 10.1136/jitc-2026-sitc2026.1184