Phase 1/2 Trial of Androgen Deprivation, with or without pTVG-AR and with or without Nivolumab, in Patients with Newly Diagnosed, High-Risk Prostate Cancer
Abstract
Prostate cancer is a significant health problem for which new treatments are urgently needed. Treatments that lower testosterone (called androgen deprivation, AD) are used when prostate cancer spreads outside of the prostate gland. While these treatments are very effective initially, they rarely cure the disease. We and other laboratories have shown that AD treatments lead to an accumulation of immune cells (called lymphocytes) within prostate tumors, at least early after treatment is started. This suggests that AD has effects on the immune system and might be combined with immune-targeted therapies, and this may improve the efficacy of AD. Our laboratory has been studying vaccines as a treatment for prostate cancer. The goal of anti-cancer vaccines is to generate lymphocytes that can recognize prostate tumor cells and kill them. We have specifically been interested in a vaccine we developed that targets the androgen receptor (AR), the protein inside prostate tumors that uses testosterone to cause tumors to grow. We have found in mouse models of prostate cancer that, if we immunize mice that have prostate tumors with this vaccine and give them AD treatment, this promotes the accumulation of lymphocytes within prostate tumors, and we see tumors respond longer to AD before the tumor starts to grow again. We have also found that, if we use vaccines in combination with another immune treatment (called PD-1 blockade), we get even stronger reactions of the vaccine-activated lymphocytes against tumors. We have studied these approaches in men with advanced prostate cancer and have recently found that this vaccine targeting the AR that we have studied in mice (called “pTVG-AR”) is safe and generates similar immune responses in men with prostate cancer. Preliminarily, it appears that men who responded to the vaccine had a longer response to the AD treatment, similar to what we found in mice. We have also found using another vaccine that combining it with PD-1 blockade (using a drug that has been approved for other kinds of cancer, but not prostate cancer) led to PSA decreases and reductions in prostate tumors detected by CT scans in men with advanced prostate cancer. Therefore, we want to test these combinations in men with very early prostate cancer, to see whether this approach of using vaccine with AD (and with or without PD-1 blockade using a drug called “nivolumab”) can both eliminate prostate cancer and set up immune “memory” to protect these individuals from having prostate cancer return later after surgery. This will be done in a clinical trial in which initially 24 men will be treated. These will be men with high-risk prostate cancer (with either a high PSA and/or high Gleason score) who are planning to undergo prostate cancer surgery. They will be randomly assigned to one of three treatments in which for 12 weeks they will receive either AD alone (using a drug called “degarelix,” six patients), or degarelix with the pTVG-AR vaccine (nine patients), or degarelix with the pTVG-AR vaccine and nivolumab (nine patients). A primary goal is to make sure these treatments are safe. Another major goal will be to determine whether these treatments are active against the cancer, and tumors removed at the time of surgery will be evaluated by the pathologist to see whether there is any remaining cancer. A secondary goal will be to follow men longer term and determine whether they remain without recurrence of the prostate cancer after 1 year. If we find that patients receiving pTVG-AR in one of the treatment groups (either with or without nivolumab) have no detectable cancer (or only a few remaining cancer cells) at the time of surgery, we will treat an additional 15 patients with that same treatment to study this further. Another goal of our research will be to see whether we can develop methods to detect changes induced by these immune treatments using a novel type of scan. We expect that this approach,
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110270
Entities
People
- Douglas McNeel
Organizations
- United States Army
- University of Wisconsin–Madison