GTL001, A Therapeutic Vaccine for Women Infected with Human Papillomavirus 16 or 18 and Normal Cervical Cytology: Results of a Phase I Clinical Trial

Purpose: Women infected with human papillomavirus (HPV) with normal cytology to mild abnormalities currently have no treatment options other than watchful waiting or surgery if highgrade cervical lesions or cancer develop. A therapeutic vaccine would offer the possibility of preventing high-grade lesions in HPV-infected women. GTL001 is a therapeutic vaccine composed of recombinant HPV16 and HPV18 E7 proteins fused to catalytically inactive Bordetella pertussis CyaA. This study examined the tolerability and immunogenicity of GTL001 in women infected with HPV16 or HPV18 with normal cytology. Experimental Design: This was a phase I trial (EudraCT No. 2010-018629-21). In an open-label part, subjects received two intradermal vaccinations 6 weeks apart of 100 or 600 mu g GTL001 + topical 5% imiquimod cream at the injection site. In a doubleblind part, subjects were randomized 2: 1: 1 to two vaccinations 6 weeks apart of 600 mg GTL001 + imiquimod, 600 mg GTL001 + placebo cream, or placebo + imiquimod. Results: Forty-seven women were included. No dropouts, treatment-related serious adverse events, or dose-limiting toxicities occurred. Local reactions were transient and mostly mild or moderate. HPV16/18 viral load decreased the most in the 600 mu g GTL001 + imiquimod group. In post hoc analyses, the 600 mu g GTL001 + imiquimod group had the highest rates of initial and sustained HPV16/18 clearance. Imiquimod increased antigenspecific T-cell response rates but not rates of solicited reactions. All subjects seroconverted to CyaA. Conclusions: For women infected with HPV16 or HPV18 with normal cervical cytology, GTL001 was immunogenic and had acceptable safety profile. (C) 2016 AACR.