GX-188E is a novel, dendritic cell targeting, DNA therapeutic vaccine encoding for HPV types 16/18- E6/E7 antigens. A previous phase I trial has been reported(1).
72 patients were enrolled on an open-label, multicenter Phase 2 trial. Eligible patients had biopsy proven CIN3 and HPV16 and/or 18 infection confirmed by PCR. GX-188E was delivered by electroporation at weeks 0, 4, and 12. The primary endpoint was a response defined as histological regression to CIN1 or less at week 20. Safety and Immunogenicity of the vaccine were also assessed. Additionally, patients could be rolled over into a continuation study for follow-up beyond 20 weeks.
72 pts were enrolled. 7 patients were dropped out or were found to be ineligible (data to be shown). 4 patients have not yet reached their 20 week f/u visit. As of January 2016, 61/72 CIN3 patients reached week 20. Of the 61 patients, 52.5% (32/61) regressed to CIN1 or less on histology at week 20. Patients with small lesion at enrollment (<50% of cervix by colposcopic inspection) were more likely to have histological regression (61.8%, 21/34) as compared to patients with lesions >50% (40.7% 11/27). The 1mg dosing group demonstrated a higher histological regression rate (64.5%, 20/31) compared to the 4 mg dosing group (40.0%, 12/30). Moreover, patients in the 1 mg group with small baseline lesions showed a regression rate of (73.3%, 11/15) and this rate increased at week 36 (88.9%, 8/9) in the follow-up study. The most common adverse events were local injection site reactions. Additional detailed analysis of safety and immunologic response assessment is ongoing.
Therapeutic vaccination with GX-188E appears well-tolerated. GX-188E vaccine shows promising activity and therapeutical potential for treatment of CIN3 and warrants continued investigation.
(1) Kim TJ, Jin H-T, Hur S-Y, et al. Clearance of persistent HPV infection and cervical lesion by therapeutic DNA vaccine in CIN3 patients. Nature Communications. 2014;5:5317. doi:10.1038/ncomms6317.