The investigational therapeutic vaccine Vvax001 was found to be safe and showed preliminary clinical effectiveness in a phase II clinical trial of patients with HPV16-positive grade 3 cervical intraepithelial neoplasia. If confirmed in a phase III trial, the vaccine may provide a nonsurgical option for premalignant cervical lesions. The study by Eerkens et al is published in Clinical Cancer Research.
Studies show that long-lasting infection with high-risk types of human papillomavirus (HPV), including HPV16 and HPV18, causes virtually all cervical cancers. A previous phase I clinical trial of Vvax001, a therapeutic vector vaccine targeting HPV16 cells expressing the E6 and/or E7 proteins, was found to induce potent anti-E6 and -E7 cytotoxic T-cell responses in patients. In a phase II study of Vvax001, the vaccine was found to be safe and showed preliminary clinical effectiveness in 18 patients with HPV16-positive grade 3 cervical intraepithelial neoplasia. If confirmed in a phase III trial, the vaccine may provide a nonsurgical option for premalignant cervical lesions.
Study Methodology
The researchers enrolled a total of 18 patients with newly diagnosed HPV16-positive grade 3 cervical intraepithelial neoplasia (CIN3). The patients received three immunizations of Vvax001 at a 3-week interval. Patients were monitored for regression of CIN3 by colposcopy up to 19 weeks following the last immunization. A colposcopy-guided biopsy was taken at the last visit and a standard-of-care loop excision was performed only in case of remaining CIN2/3.
Histopathologic response rates, HPV16 clearance, treatment-related adverse events, and vaccine-induced immune responses were assessed.
Results
Upon colposcopy examination the researchers found a reduction in CIN3 lesion sizes in 17 of 18 patients (94%) that was already evident from 3 weeks onward after their last immunization. A histopathologic complete response (regression to CIN1 or no dysplasia) was observed in 9 of 18 patients (50%), and HPV16 clearance in 10 of 16 patients (63%). The vaccine did not induce clearance of other HPV types.
To date, the researchers have observed no recurrences, with a median and longest disease-free survival of 20 and 30 months, respectively. No serious adverse events were observed.
“Treatment with Vvax001 is safe, feasible, and show preliminary clinical effectiveness in patients with HPV16-associated CIN3 lesions,” concluded the study authors.
Translational Significance
“To the best of our knowledge, this response rate makes Vvax001 one of the most effective therapeutic vaccines for HPV16-associated CIN3 lesions reported to date,” said Refika Yigit, MD, the principal investigator of this study, and an oncology gynecologist at the University Medical Centre Groningen in the Netherlands, in a statement. “If confirmed in a larger trial, our results could mean that at least half of the patients with CIN3 might be able to omit surgery and avoid all its possible side effects and complications.”
Dr. Yigit, of the University Medical Centre Groningen in the Netherlands, is the corresponding author of this study.
Disclosures: Funding for this study was provided by the Dutch Cancer Society and ViciniVax. The study authors’ conflict of interest statements may be found at aacrjournals.org.
