VGX-3100 DNA immunotherapy shows higher regression in HPV cervical lesions

DNA Immunotherapy Generates Higher Regression Rates in HPV-Associated Cervical Lesions

Patients receiving the investigational DNA immunotherapy VGX-3100 for human papillomavirus types 16 and 18-associated cervical high-grade squamous intraepithelial lesions experienced higher rates of histological regression than those given a placebo, according to data presented at the 2026 Society for Immunotherapy of Cancer Annual Meeting in Phoenix, Arizona.

Key Clinical Takeaways:

• By week 36, an independent pathology committee determined normal histology in 70 participants within the VGX-3100 group, contrasted with 26 participants in the placebo group.
• Treatment-related adverse events occurred in 84.2% of patients in the treatment arm and 85.3% of those in the placebo group, with most reactions localized to the injection site.
• The modified intention-to-treat population included patients who completed all three doses and at least one efficacy assessment following treatment.

Patient Demographics and Baseline Characteristics in Trial

The randomized, double-blind, placebo-controlled Phase III trial, designated HPV-303CHN, enrolled patients with a mean age of 31.7 years in the VGX-3100 arm and 33.1 years in the placebo arm. Baseline assessments indicated that 55.4% of patients in the treatment group and 57.4% in the control group had cervical intraepithelial neoplasia grade 3. 94.2% of the treatment group and 95.6% of the placebo group were HPV-16 positive, while smaller percentages presented with HPV-18 or other high-risk viral types. Prior HPV vaccination was documented in 28.1% of the VGX-3100 cohort and 27.9% of the control cohort.

The modified intention-to-treat population comprised participants who completed all three scheduled doses and underwent at least one post-treatment efficacy evaluation. Individuals who underwent an unscheduled biopsy or alternative therapeutic intervention prior to week 36, or whose records were missing at that interval, were classified as nonresponders. Follow-up protocols for the trial extend through week 88.

Histological Outcomes Across Subgroups

Histological evaluation at week 36 revealed distinct differences between the treatment and control arms. Beyond the 70 normal histology findings in the VGX-3100 group versus 26 in the placebo group, CIN1 was recorded in 17 treatment patients and 9 control patients. CIN2 was observed in 20 treatment patients and 11 control patients, while CIN3 appeared in 20 treatment participants and 16 placebo participants. Histology data remained missing for 11 patients in the active arm and 6 in the placebo arm.

Immune System Response Correlates

Biological assessments demonstrated that VGX-3100 elicited stronger antibody and T-cell responses against HPV at weeks 15 and 36 than the placebo. Investigators noted higher HPV-16 and HPV-18 E7 antibody titers alongside increased HPV-16/18 E6/E7-specific interferon-gamma ELISpot activity.

Among participants with baseline CIN3 who received the immunotherapy, 60.0% of responders showed an increase in HPV-16 E7-specific ELISpot responses between baseline and week 15, compared with 32.4% of nonresponders. Furthermore, individuals achieving a response within this particular cohort also displayed more pronounced elevations in CD8+CD69+, CD8+CD137+, and CD8+PD-1+ T-cell populations. Exploratory analysis indicated that week 15 HPV-16 E7 spot-forming units discriminated responders from nonresponders with an area under the curve of 0.715.

Adverse Event Rates Observed in Participants

Any-grade adverse events occurred in 94.2% of patients in the VGX-3100 arm and 94.1% of those in the placebo arm within the safety population. Treatment-related adverse events were reported in 84.2% of the active treatment group and 85.3% of the control group. Drug-related adverse events affected 30.9% of VGX-3100 recipients compared with 48.5% of placebo recipients, while device-related events occurred in 84.2% and 85.3% of patients, respectively. Skolnik noted that the majority of adverse events reflected transient, grade 1 or grade 2 local reactions at the injection site.

Serious adverse events emerged in 3.6% of the treatment arm and 2.9% of the placebo arm, with none classified as treatment-related. Grade 3 or higher adverse events affected 6.5% of patients in the VGX-3100 group and 8.8% in the placebo group. No grade 3 or higher treatment-related adverse events occurred in the active arm, whereas one such event occurred in the control arm. Neither study arm recorded adverse events of special interest or grade 5 adverse events. One patient in the VGX-3100 arm withdrew after a diagnosis of invasive squamous cell carcinoma at week 36, which investigators determined was unrelated to the study treatment.

Ongoing Safety Follow-Up and Platform Context

Participants in the HPV-303CHN trial continue their scheduled follow-up assessments through week 88 to build out long-term safety and tolerability profiles. These findings follow the October 30, 2026, accelerated approval granted by the FDA for doruxapapogene ralaplasmid and lalikinogene sifuplasmid-gxfd (Voceryq; formerly INO-3107), a DNA immunotherapy developed by Inovio that utilizes the same platform technology to reduce surgical intervention frequency in adults with recurrent respiratory papillomatosis.

Disclaimer: The information provided in this article is for educational and scientific communication purposes only and does not constitute medical advice. Always consult with a qualified healthcare provider regarding any medical condition, diagnosis, or treatment plan.