Vvax001, a Therapeutic Vaccine, for Patients with HPV16-Positive High-grade Cervical Intraepithelial Neoplasia: A Phase II Trial

Abstract

Purpose: Human papillomavirus (HPV) infection is the major HPV16 clearance, treatment-related adverse events, and vaccine-cause of (pre)malignant cervical lesions. We previously demon- induced immune responses were assessed. strated that Vvax001, a replication-incompetent Semliki Forest Results: A total of 18 patients were enrolled and fully imvirus vaccine encoding HPV type 16 (HPV16) E6 and E7, in- munized. Colposcopic examination revealed a reduction in duced potent anti-E6 and -E7 cytotoxic T-cell responses. In this CIN3 lesion sizes in 17/18 (94%) patients already evident study, we investigated the clinical efficacy of Vvax001 in patients from 3 weeks onward after the last immunization. A histowith HPV16-positive cervical intraepithelial neoplasia (CIN) pathologic complete response (regression to CIN grade 1 or grade 3 (CIN3). no dysplasia) was observed in 9/18 patients (50%) and Patients and Methods: Patients with newly diagnosed HPV16- HPV16 clearance in 10/16 patients (63%). Vvax001 did not positive CIN3 were eligible for participation. Patients received induce clearance of other HPV types. To date, no recurrences three immunizations of Vvax001 (5 ͓ 107 infectious particles) at have been observed, with a median and longest disease-free a 3-week interval. Up to 19 weeks after the last immunization, survival of 20 and 30 months, respectively. No serious adverse patients were monitored for regression of CIN3 by colposcopy. A events were observed. colposcopy-guided biopsy was taken at the last visit, and a Conclusions: Treatment with Vvax001 is safe and feasible and standard-of-care loop excision was performed only in case of shows preliminary clinical effectiveness in patients with HPV16-remaining CIN grade 2/CIN3. Histopathologic response rates, associated CIN3 lesions. ►