New prostate cancer “vaccine” in Phase II trial prior to ADT


According to a media release we saw this morning, a company called Madison Vaccines has started a Phase II clinical trial of a new form of immunotherapy for treatment of men with non-metastatic prostate cancer and rising PSA levels prior to any treatment with androgen deprivation therapy (ADT).

Based on the media release, and on a brief conversation with a senior executive from Madison Vaccines, here is what we think we know about the product that is being tested and the trial that is being conducted:

  • The product is known (at this time) both as MVI-816 and as pTVG-HP. (It depends where you look.)
  • MVI-816 is a plasmid DNA vaccine (i.e.,  it is made using purified forms of circular bacterial DNA, known as “plasmids” that are modified to contain human genetic material, and which therefore have the theoretical ability to induce an immune response to a specific type of cancer).
  • Phase I trials of MVI-816 have been completed; those Phase I trials demonstrated that MVI-816 was safe, and that the product
    • Induced antigen-specific CD8+ cytotoxic T-cell immunological responses
    • Slowed PSA doubling times in > 30 percent of patients enrolled
  • The trial discussed in the media release is  a randomized, double-blind, Phase II trial designed to test the ability of MVI-816 + granulocyte macrophage colony-stimulating factor (GM-CSF) to delay progression of prostate cancer in men with a rising PSA after definitive first-line treatment (i.e., prostatectomy or radiation therapy given with curative intent)
  • Such patients must have a PSA doubling time of ≤ 12 months.
  • Trial endpoints include
    • Rates of metastasis-free survival at 24 months
    • Changes in median time to disease progression
  • Patients will be randomized to treatment with either MVI-816 + GM-CSF or GM-CSF alone.

We are assuming that the current trial is being carried out exclusively at centers in the USA, but information about this trial is not yet available on the ClinicalTrials.gov web site, so there are a lot of other details about this trial that we do not know.

There is a brief outline of the trial protocol at the one center we know of at which the trial is being conducted (the University of Wisconsin Carbone Cancer Center in Madison, WI). We also know (based on the outline of the trial protocol) that this is a 1:1 randomization (meaning that you have an equal chance of getting either MVI-816 + GM-CSF or just GM-CSF alone), but examples of other things we can’t tell you (because we don’t yet know) include:

  • How many or which other centers are enrolling patients into this trial
  • The total number of patients to be enrolled in the study

For patients seeking that type of information, you will need to contact the company directly — either by phone (at 1-608-467-5269) or using the electronic contact system on the company’s web site.

2 Responses

  1. AN IMMUNE SYSTEM DOUBLE COMBINATION?

    I’m thinking the GM-CSF drug is Leukine, and GM-CSF is also used in Provenge. If so, then the Phase II trial would be testing the new immune system agent plus Leukine against Leukine alone, doing all of it in an ADT-naive population of recurring patients. Is that right?

    This new combination is meant to compete with IADT for recurring patients. That means, to find a place in the therapeutic arsenal, it would need to show a superior side effect profile (ADT side effect countermeasure effectiveness/compliance as part of the context), superior effectiveness in controlling the cancer (which would await the Phase III trial as the Phase II trial is far too short to go up against well done IADT), or ideally both.

  2. Dear Jim:

    You may be “a step too far” here. The developers would probably tell you that this investigational drug combination is actually being tested prior to any form of second-line therapy (e.g., radiation therapy in a man with a rising PSA post-surgery).

    This would imply that a potential endpoint of any Phase III trial (if and when they get to that stage) might be deferral of time to the need for any form of second or third-line therapy … if the FDA would “buy” that as a primary endpoint (and I have my doubts about that).

    I suspect that everyone will need to see some very clear suggestions of clinical impact from this Phase II trial before the developers and the FDA start to think hard about what any endpoint might be for a Phase III trial … and exactly how to define a set of patients who would be appropriate participants in such a trial.

    The problem with a therapy like this one is that unless it really works to delay metastasis within a couple of years in a well-defined group of patients with aggressively progressive disease, it could take a decade or more to prove the clinical benefit in a clinical trial. That is unlikely to be practical for a developer. On the other hand, the patients who may get the greatest benefit from a treatment like this are the ones with progressive disease after first-line therapy that is not so aggressive, and who may, therefore, be able to use such a treatment to delay the onset of metastasis for years and years.

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