Phase 1b/2, Randomised, Placebo-controlled Study to Evaluate Safety, Tolerability, Efficacy, and Immunogenicity of VTP-200, a Chimpanzee Adenovirus and Modified Vaccinia Ankara-vectored Multigenotype High-risk Human Papillomavirus Vaccine in Women With Low-grade Cervical Lesions
Hellner K., Simon P., De Sutter P., Vahula K-L., Briggs P., Kiisla Ü., Russell M., Newton C., Dewilde K., Anderson K., Kopycinski J., Vardeu A., Davis C., Sebastian S., Kennerley R., Wheeler V., Jones B., Tait D., Downs M., Dorrell L., Hancock G., Cuschieri K., Evans T.
Abstract Background The clearance of high-risk oncogenic human papillomaviruses (hrHPV) and related cervical lesions is associated with the development of a robust T-cell response. Therapeutic vaccination that induces HPV antigen-specific T cells is a promising approach. Method A 2-vector dosing strategy using Chimpanzee Adenovirus Oxford 1-HPV and Modified Vaccinia virus Ankara-HPV, both encoding the same multiantigen HPV cassette was given on a 0/28-day schedule to participants with persistent cervical hrHPV and a history of low-grade cervical lesions. An open-label lead-in was followed by a randomized, blinded, placebo-controlled main phase. The primary endpoint was the safety of the different dose regimens; secondary endpoints included immunogenicity, and clearance of hrHPV and associated lesions at 12 months. Nine participants were enrolled in the lead-in and 99 were randomized 67:32 to 5 active dose arms or placebo, respectively. Results The regimens were well-tolerated with no grade 3–related treatment emergent adverse events or serious adverse reactions. All dosing regimens generated antigen-specific CD4+ and CD8+ T-cell responses. There was no difference in hrHPV clearance between the pooled active groups and placebo (20/64 [31.3%] versus 10/30 [33.3%]; P > .99), nor in lesion clearance. A trend toward higher hrHPV clearance (60%) was observed with the highest Chimpanzee Adenovirus Oxford 1-HPV doses. No association between the peripheral immune response and clearance was demonstrated. Conclusions A heterologous, multiantigenic HPV 2-component immunotherapy regimen was well-tolerated and immunogenic but did not result in a statistically significant clearance of either hrHPV or the associated cervical lesions in women with persistent high-risk HPV infections. Trial registration EudraCT 2019-001890-98; NCT04607850