Phase I/II open label nonrandomized safety and efficacy study of the viral vectored ChAdOx1-MVA 5T4 immunotherapy in combination with PD-1 checkpoint blockade in intermediate-risk localized or locally advanced prostate cancer and advanced metastatic prostate cancer.

Abstract

TPS3170 Background: Antigen-specific immunotherapy (Sipuleucel-T) is licenced for the treatment for castrate resistant prostate cancer, but has modest clinical efficacy and is complex to administer to patients. New therapeutic antigen-specific approaches are required to generate and sustain therapeutic immune responses against tumour specific antigens in men with early and advanced prostate cancer. We have previously reported immunogenicity and efficacy data of a novel viral vectored vaccines-based immunotherapy 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. We tested this immunotherapy alone in a first-in-human trial, VANCE (NCT02390063), in intermediate risk prostate cancer patients. Based on encouraging safety and exceptional T cell immunogenicity of the VANCE study, the phase I/II trial, ADVANCE (NCT03815942) is being undertaken to test the immunotherapy safety and efficacy in combination with PD-1 blockade in intermediate risk disease and metastatic prostate cancer. Methods: Study design: ADVANCE, an open label non-randomised phase I/II study, will recruit 12 patients with intermediate-risk prostate cancer patients (Gleason score ≤ 7, local tumour stage ≤T3c, PSA≤ 20 ng/ml) scheduled to undergo radical prostatectomy (Cohort 1) and 24 mCRPC patients with disease progression on anti-androgen therapy with either enzalutamide or abiraterone (Cohort 2). Cohort 1 will receive one cycle of ChAdOx1-MVA 5T4 immunotherapy and a single nivolumab infusion. Cohort 2 will receive 2 cycles of ChAdOx1-MVA 5T4 vaccination and three nivolumab infusions. Primary endpoint: Cohort 1 - PSA change from baseline to surgery, Cohort 2 – composite response rate measured as either ≥50% reduction of circulating tumour DNA or ≥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. 23 of planned 24 patients have been enrolled in Cohort 2. Enrolment to the Cohort 1 is ongoing. The data analysis is expected to be completed by Q4 2020 for Cohort 2. Clinical trial information: NCT03815942 .