Phase 2 trial of a therapeutic vaccine for HPV16-positive high-grade cervical intraepithelial neoplasia

Vvax001 is a replication-incompetent Semliki Forest virus vaccine encoding HPV type 16 E6 and E7 proteins and inducing potent anti-E6 and –E7 cytotoxic T-cell responses. A phase 2 trial at the University Medical Center Groningen (The Netherlands) evaluated Vvax001 for newly diagnosed HPV16-positive cervical intraepithelial neoplasia grade 3 (CIN3). Patients received 3 immunizations of Vvax001. Colposcopic examination revealed a reduction in CIN3 lesion size in 17 of 18 patients (94%) already evident from 3 weeks onwards after the last immunization. Histopathological complete response (regression to CIN1 or no dysplasia) was seen in 9 of 18 patients (50%) andHPV16 clearance in 10 of 16 patients (63%). Vvax001 did not induce clearance of other HPV types. At the date of this analysis, no recurrences have been seen, with median and longest disease-free survival of 20 and 30 months, respectively. No serious adverse events occurred. The authors conclude that treatment with Vvax001 was safe and feasible and showed preliminary clinical efficacy in patients with HPV-associated CIN3 lesions.