PROSTVAC in Combination With Nivolumab in Men With Prostate Cancer

Summary

Participation Requirements

Description

Background: Immune checkpoint inhibitors interfere with the immune system s autoregulatory mechanisms, allowing for a potentially expanded and prolonged T-cell response with the possibility of greater antitumor effects. Nivolumab is a fully human IgG4 monoclonal antibody that targets the PD-1 protei...

Background: Immune checkpoint inhibitors interfere with the immune system s autoregulatory mechanisms, allowing for a potentially expanded and prolonged T-cell response with the possibility of greater antitumor effects. Nivolumab is a fully human IgG4 monoclonal antibody that targets the PD-1 protein. Specifically, the antibody binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, thereby releasing PD-1 pathway-mediated inhibition of the immune response, including anti-tumor immune response. PROSTVAC (developed by the National Cancer Institute [NCI] and licensed to Bavarian Nordic Immunotherapeutics, Mountain View, CA) is a therapeutic cancer vaccine for prostate cancer. Early studies have demonstrated immunologic efficacy and suggested clinical benefit. A phase III trial has completed accrual. A previous study combining the immune checkpoint inhibitor ipilimumab and PROSTVAC suggested greater efficacy than PROSTVAC alone. Additional studies have demonstrated the potential efficacy of immunologic combination therapy with the immune checkpoint inhibitor nivolumab. This study will aim to evaluate the impact of the combination of PROSTVAC and the immune checkpoint inhibitor nivolumab on the tumor microenvironment focusing on immune cell infiltration as the primary endpoint. US-MRI imaging technology will be employed to sample the tumor before treatment and after radical prostatectomy. The findings from this study could serve as the basis for future studies with this combination in this population of patients and more advanced disease. Objectives: Safety (For castration resistant prostate cancer (CRPC) lead-in cohort) Evaluate changes in T-cell infiltration in the tumor after neoadjuvant treatment with PROSTVAC and nivolumab, relative to changes seen in a phase 2 trial with PROSTVAC alone in the neoadjuvant setting- NCT02153918 (For the neoadjuvant cohort). Eligibility: Patients must have histopathological documentation of adenocarcinoma of the prostate prior to starting this study and evaluable biopsy tissue (e.g., unstained slides or blocks) available for analysis. For the castration resistant lead in cohort, if histopathological documentation is unavailable, a rising PSA and a clinical course consistent with prostate cancer would be acceptable. Patients must have a performance status of 0 to 1 according to the ECOG criteria. Hematological eligibility parameters (within 16 days of starting therapy): Granulocyte count 1,500/mm^3 Platelet count 100,000/mm^3 Hgb greater than or equal to 8 g/dL Biochemical eligibility parameters (within 16 days of starting therapy): Hepatic function: Bilirubin < 1.5 mg/dl (OR in patients with Gilbert's syndrome, total bilirubin less than or equal to 3.0 mg/dL), AST and ALT less than or equal to 2.5 times upper limit of normal. Creatinine less than or equal to 1.5 X ULN Design: The primary focus of this study will be to evaluate PROSTVAC and nivolumab in the neoadjuvant setting. Lead-in cohort evaluating the safety and tolerability of this combination in the castration resistant setting (CRPC cohort) Following this lead-in cohort in the CRPC setting, we will enroll a cohort in the neoadjuvant setting evaluating the combination of PROSTVAC and nivolumab. The lead-in safety cohort will require 10 patients and the neoadjuvant cohort will require 17 evaluable patients. In order to allow for a small number of inevaluable patients, the accrual ceiling will be set to 29 patients.

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