Abstract 881TiP
Background
HPV16 accounts for almost 60% of the cervical cancer cases. There is an urgent need to develop therapeutic HPV vaccines for control of chronic HPV infection and associated malignancies. HPV16 oncogenes E6/E7 are truly cancer-specific viral antigens and represent ideal targets for a therapeutic HPV16 vaccine. VB10.16 is a targeted DNA-based immunotherapy designed to treat HPV16-associated pre- and malignant lesions. The DNA vaccine encodes a recombinant protein consisting of mutation-inactivated E6 and E7 proteins linked to the natural human chemokine macrophage inflammatory protein-1 alpha (MIP-1α). Atezolizumab is a PD-L1 inhibitor indicated for the treatment of urothelial carcinoma, non- small cell and small cell lung cancers and triple negative breast cancer, with ongoing investigation as a single agent and combination therapy for many other tumour types. In a phase I trial, VB10.16 monotherapy demonstrated a beneficial safety and efficacy profile and upregulated PD-L1 in the least responsive patients. This provides a strong rationale for combining VB10.16 with a checkpoint inhibitor therapy.
Trial design
This open-label phase II trial is designed to evaluate the safety and efficacy of multiple dosing with VB10.16 immunotherapy in combination with atezolizumab in patients with advanced or recurrent non-resectable HPV16+ cervical cancer, who failed or are not eligible for current standard of care. Primary objectives are to assess the safety/tolerability and overall response rate of VB10.16 immunotherapy in combination with atezolizumab. Secondary objectives are to assess the immunogenicity of multiple doses of VB10.16 immunotherapy in combination with atezolizumab and to further assess efficacy by progression-free survival, duration of response and overall survival. The exploratory objectives are to investigate predictive biomarkers and changes in the tumour microenvironment during therapy and to evaluate the relationship between HPV16 circulating tumour DNA and clinical response. The study will enrol 50 patients and is approved in 6 European countries and open for enrolment in Norway. (EUDRACT Number:2019-002328-33).
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Vaccibody AS.
Funding
Vaccibody AS.
Disclosure
B. Nicolaisen, K. Schetne, S. Torhaug: Full/Part-time employment: Vaccibody AS. A.B. Fredriksen: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Vaccibody AS. All other authors have declared no conflicts of interest.