Abstract 682P
Background
New therapeutic antigen-specific approaches are required to generate and sustain therapeutic immune responses against tumour specific antigens in men with advanced prostate cancer. We have previously reported efficacy data on a novel vaccine based on two replication-deficient viruses, chimpanzee adenovirus (ChAdOx1) and MVA, targeting an oncofetal self-antigen 5T4, administered as a single agent and in combination with anti-PD-1 in mouse tumour models. Based on encouraging safety and exceptional T cell immunogenicity of the VANCE study (NCT02390063), the phase I/II trial, ADVANCE (NCT03815942) was undertaken to test the vaccine safety and efficacy in combination with PD-1 blockade in metastatic castrate-resistant prostate cancer (mCPRC).
Methods
ADVANCE recruited mCRPC patients with disease progression on anti-androgen therapy with either enzalutamide or abiraterone. Patients received 2 cycles of ChAdOx1-MVA 5T4 (VTP-800) vaccination and three nivolumab infusions. The primary endpoint is a composite response rate measured as either a 50% reduction of circulating tumour DNA or a 50% serum PSA decrease from baseline at 24-week assessment and the maximal response rate. Secondary and exploratory endpoints include 5T4-specific immune response in the periphery, progression-free and overall survival and reduction of circulating tumour cells.
Results
23 patients were recruited (- the trial is now closed to recruitment -) and met the endpoint for performing the first data analysis. Of 23 mCRPC patients who received VTP-800 in conjunction with an anti-PD-1, 5 patients (22%) had a >50% reduction in PSA level at any time point compared to the baseline (median of 88 ng/ml). VTP-800 and Nivolumab treatment were well tolerated.
Conclusions
VTP-800 and Nivolumab treatment led to a >50% reduction in PSA in 22% of patients in the ADVANCE trial and were well tolerated. Analysis of safety data, changes in circulated tumour DNA, 5T4-specific immune response in the periphery, progression-free and overall survival and reduction of circulating tumour cells are ongoing and will be presented at the meeting.
Clinical trial identification
NCT03815942.
Editorial acknowledgement
No editorial assistance was provided by a third party.
Legal entity responsible for the study
University of Oxford.
Funding
European Union Seventh Framework Programme under grant Agreement No. 602705 (Project IMPROVE) and Vaccitech Ltd.
Disclosure
M. Tuthill: Advisory/Consultancy: Vaccitech Limited; Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis, ; Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: Lilly; Advisory/Consultancy: Oxford Vacmedix, ; Speaker Bureau/Expert testimony: Astellas; Speaker Bureau/Expert testimony: Genomic Health; Speaker Bureau/Expert testimony: Esai; Speaker Bureau/Expert testimony: Everything Genetic; Travel/Accommodation/Expenses: EUSA Pharma. T. Evans: Leadership role, Shareholder/Stockholder/Stock options: Vaccitech Limited. A. Protheroe: Speaker Bureau/Expert testimony: BMS. A.V.S. Hill: Advisory/Consultancy, Founder Vaccitech: Vaccitech Limited. All other authors have declared no conflicts of interest.