MVI-816 (pTVG-HP) – Plasmid DNA vaccine designed to activate patients’ immune systems to kill prostate cancer cells.
TARGET: prostatic acid phosphatase (PAP), a well-defined prostate antigen suitable for prostate cancer vaccines. MVI is testing the hypothesis that vaccination with MVI-816 will provide clinical benefit when used in the minimal residual disease setting, before overt metastases can be detected by standard imaging technologies in patients with prostate cancer.
INDICATION: Biochemically Recurrent Prostate Cancer. Men with rapidly rising PSA after prostatectomy or radiation therapy for curative intent are at especially high risk for development of bone metastases. Once metastatic to bone, prostate cancer is incurable and frequently fatal.
CLINICAL STATUS: Two Phase 1 trials have been completed. Good safety and persistent PAP-specific Th1-biased immune responses were observed in patients with early recurrent prostate cancer. Favorable changes (slowing) in patient PSA doubling times were observed after vaccination in 30-40% of Phase 1 patients. MVI-816 is currently progressing in a randomized, double blinded, placebo controlled Phase 2 trial in hormone naïve, non-metastatic prostate cancer patients with PSA DT <12 months. The primary endpoint is metastasis free survival at 24 months.
MVI-118 (pTVG-AR) is a second DNA vaccine being developed by MVI.
TARGET: This vaccine targets the human androgen receptor, the critical biological target responsible for driving prostate cancer progression and, in many cases, resistance to current therapies. Castration therapy-resistant prostate cancer cells, with high level AR up-regulation, should be ideal targets for Th-1-biased CTL killing induced by immunization with MVI-118. MVI-118 demonstrated increased survival in a transgenic model of prostate cancer in the absence of observable toxicities.
INDICATION: Metastatic Prostate Cancer. Standard of care for men with newly diagnosed metastatic prostate cancer is most commonly hormonal or physical castration. Some non-metastatic, but biochemically recurrent prostate cancer patients will also elect to begin castration therapy in advance of detectable bone metastases. Although tumor regressions and symptomatic relief is commonly achieved using these therapies, the majority of patients will develop castrate resistant disease, frequently as the result of high level up-regulation of the androgen receptor (AR).
CLINICAL STATUS: MVI anticipates a Phase 1 IND filing in 2014. Phase 1 will explore safety, dose regimen, and immunological markers of activity in newly metastatic prostate cancer patients who are initiating androgen deprivation therapy. MVI-118 cGMP manufacturing is underway as are IND-enabling preclinical toxicology studies.
Companion Diagnostic Test
Research on blood samples from MVI-816 phase 1 clinical studies revealed a CD8+, CTLA4+ regulatory T-cell signature that suppressed detection of PAP-specific T-cell effector functions in certain patients. PAP-specific CD8+ regulatory T-cells were also detected prior to immunization in some patients in the absence of PAP-specific effector responses.
MVI will conduct further research to determine if this novel signature is reproducible and robust, and whether it may be generally applied in other vaccine settings (e.g., in patients immunized with the AR vaccine) as a tool to identify patients who are predisposed to mount an efficient vaccine response.