MVI-816

MVI-816 is a prostatic acid phosphatase encoding DNA plasmid vaccine.

• Men with rapidly rising PSA after prostatectomy or radiation therapy for curative intent who are at especially high risk for development of distant soft tissue and bone metastases. Once metastatic to bone, prostate cancer is incurable.
• Men with non-metastatic and metastatic prostate cancer, in combination with checkpoint inhibitors, to delay disease progression and improve overall survival.

Multiple Phase 1 trials with MVI-816 are complete, revealing strong safety and tolerability as well as favorable changes in PSA and PSA doubling times.  

As monotherapy, MVI-816 demonstrated delayed development of metastases vs. placebo in men with aggressive non-metastatic, PSA-recurrent prostate cancer (PSA doubling times < 3 months).  

Patients on placebo showed increasing NaF uptake from baseline by micrometastatic bone lesions in this trial, while patients on MVI-816 showed decreased uptake of NaF from baseline over the same time period.  

In combination clinical trials combining MVI-816 + pembrolizumab in men with mCRPC, PSA declines below baseline are observed at a higher rate than reported using pembrolizumab alone.

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Prostatic acid phosphatase (PAP) is a prostate cancer antigen, and has become a model antigen for active immunotherapies targeting prostate cancer. PAP was one of the first proteins detected in the serum of patients with cancer to be identified as a potential serum marker. It was subsequently shown to have expression essentially restricted to normal and malignant prostate tissue, and immunohistochemical staining for PAP is still performed to establish a prostate origin of metastatic adenocarcinoma. Detection of serum PAP has been essentially replaced by serum prostate-specific antigen (PSA) as a cancer biomarker, given the sensitivity of the latter marker for prostate cancer progression. PSA and prostate-specific membrane antigen (PSMA) are two other proteins being investigated as prostate tumor antigens. However, PSMA expression has been identified in several normal nonprostate tissues, making it potentially a less specific target than PAP or PSA for anti-prostate tumor vaccines. The presence of a rat homolog of PAP has provided an animal model for testing the efficacy of vaccines in preclinical models, making this a particularly attractive prostate-specific target antigen. In addition, while there has been significant interest in PSA as an antigen in anti-tumor vaccines, targeting PAP has a potential advantage by permitting the measurement of serum PSA as a biomarker for clinical response without potentially confounding this analysis by also targeting it immunologically. Several vaccines targeting PAP have entered clinical testing. Results from a trial targeting PAP by means of an antigen-presenting cell vaccine approach have suggested clinical benefit in terms of overall survival, and a confirmatory phase III randomized trial to test this approach inpatients with advanced, metastatic prostate cancer was completed with results confirming the earlier suggestion that patients receiving vaccine survive longer than patients not receiving vaccine.