Phase I/II Trial of Androgen Deprivation, With or Without pTVG-AR, and With or Without T-Cell Checkpoint Blockade, in Patients With Newly Diagnosed, High-Risk Prostate Cancer
University of Wisconsin, Madison
Summary
The current protocol will examine the use of a plasmid DNA vaccine encoding AR, alone or with T-cell checkpoint blockade, to induce and/or augment therapeutic T-cells following androgen deprivation in patients with newly diagnosed prostate cancer scheduled to undergo prostatectomy. Patients without evidence of metastatic disease, with tissue remaining from a pre-treatment biopsy, and who are being considered for standard treatment by prostatectomy, will be invited to participate and will be on study for up to 15 months.
Description
The original design of this protocol was to examine the use of a plasmid DNA vaccine encoding Androgen Receptor (AR), alone or with nivolumab, to induce and/or augment therapeutic T-cells following androgen deprivation in participants with newly diagnosed prostate cancer scheduled to undergo prostatectomy in one of three treatment arms. Based on emerging preclinical data that the timing of PD-1 blockade with the first immunization may be critical, and that combining PD-1 and LAG-3 blockade can improve the anti-tumor efficacy of vaccination in murine models of prostate cancer, the trial was ame…
Eligibility
- Age range
- 18+ years
- Sex
- Male
- Healthy volunteers
- No
Inclusion Criteria: * Histologically confirmed adenocarcinoma of the prostate * Patients must be considered candidates for prostatectomy as per standard of care * High-risk patients for recurrent disease, with high risk defined based on one of the following criteria: * Gleason score 7 and baseline serum prostate specific antigen (PSA) \> 20 ng/mL * Gleason score \> 7 * Life expectancy of at least 12 months at screening * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Adequate hematologic, renal and liver function as evidenced by the following within 4 weeks of…
Interventions
- DrugDegarelix
standard Gonadotropin-releasing hormone (GnRH) antagonist
- BiologicalpTVG-AR
DNA vaccine encoding androgen receptor ligand-binding domain
- DrugNivolumab
Nivolumab is a human programmed death receptor-1 (PD-1)-blocking antibody indicated for the treatment of patients with multiple different types of cancer.
- DrugCemiplimab
Cemiplimab is a human PD-1 blocking antibody approved for the treatment of patients with non-small cell lung cancer, cutaneous squamous cell carcinoma, and locally advanced basal cell carcinoma.
- DrugFianlimab
Lymphocyte activation gene-3 (LAG-3) is a protein that is upregulated on activated CD4+ and CD8+ T cells following T-cell receptor engagement. Binding of LAG-3 to MHC II on professional antigen-presenting cells suppresses the proliferation, activation, and cytokine secretion of T cells. Fianlimab is a human IgG4 antibody to lymphocyte activation gene-3 (LAG-3) that blocks LAG-3/MHC II-mediated T-cell inhibition.
- Drug
Location
- University of Wisconsin Carbone Cancer CenterMadison, Wisconsin