A phase 2, prospective, randomized, multicenter, open-label study of GX-188E, an HPV DNA vaccine, in patients with cervical intraepithelial neoplasia 3

Purpose: To determine the efficacy of the therapeutic DNA vaccine GX-188E for inducing regression of cervical intraepithelial neoplasia (CIN) 3. Experimental Design: We conducted a prospective, randomized, multicenter, open-label, phase 2 clinical trial of GX-188E in CIN3 patients positive for HPV type 16/18. The primary endpoint was to determine the histopathological regression to less than or equal to CIN1 at visit 7 (V7; 20 weeks after the first GX-188E injection), and an extension study was pursued until visit 8 (V8; 36 weeks after the first GX-188E injection). HPV sequencing analysis and an ex vivo IFN-γ ELISPOT assay were performed using the collected cervical biopsy and blood samples from patients. Results: In total, 72 patients were enrolled and underwent randomization. Of them, 64 patients were included in per-protocol analysis (V7) and 52 in extension analysis (V8). Our data showed 52% (33/64) at V7 and 67% (35/52) of patients at V8 presented histopathological regression after receiving the GX-188E injection. We found that 73% (V7) and 77% (V8) of the patients with histological regression showed HPV clearance. HPV clearance and histopathological regression were significantly associated at V7 and at V8. Compared to the measurements at V1 (baseline), the patients at V8 with HPV clearance showed significantly higher fold-changes in their IFN-γ ELISPOT responses compared to those without HPV clearance. The HPV sequence analysis revealed that the HPV type 16 E6/E7 variants D25E, V83L, and N29S were inversely associated with histopathological regression at V8. Conclusions: GX-188E is an effective therapeutic vaccine against a cohort containing only CIN3 patients.