The potential of MVA-5T4 as treatment for advanced prostate cancer

Early data have suggested that a modified vaccinia Ankara (MVA) virus that expresses a tumor-associated glycoprotein called 5T4 may have activity in the treatment of men with metastatic, castration-resistant prostate cancer (mCRPC) — among other forms of cancer. We will refer to this agent as MVA-5T4; the brand name is TroVax®.

Last year, a paper by Abern et al. in OncoTargets and Therapy gave an overview of the rationale behind why MVA-5T4 may have activity in the treatment of advanced forms of prostate cancer. In this paper, the authors also summarized early data from an open-label, Phase II trial in 27 patients with mCRPC patients who had been treated with MVA-5T4 alone (n = 14) or with MVA-5T4 and 12 cycles of GM-CSF (n = 13). All 27 patients had received prior therapy with androgen deprivation and with docetaxel-based chemotherapy. Men with a low performance status and/or autoimmune disease were not eligible for inclusion in the trial.

The results reported at that time were as follows:

  • There were no grade 3 or 4 toxicities in either arm of the trial.
  • The most common adverse event reported was injection site irritation.
  • 24/27 patients (89 percent) were evaluable for measurement of immune response.
  • 24/24 evaluable patients (100 percent had anti-5T4 antibody responses.
  • 15/27 patients (56 percent) had a period of PSA stabilization.
  • 6/27 patients 22 percent) had a decreased PSA velocity.
  • 5/13 patients in the MVA-5T4 + GM-CSF arm (38 percent) had a transient 4-week decrease in PSA of 30 percent or more that was attributed to the GM-CSF.
  • No patients in the MVA-5T4 alone arm had a PSA decline.
  • There were no objective responses based on CT or bone scans in either treatment arm.
  • However, patients in the MVA-5T4 alone arm had an increased time to progression compared with the patients in the MVA-5T4 + GM-CSF arm (4.05 months vs 2.1 months, P = 0.0125).

In a second paper, by Amato and Stepankiw, in Clinical Medical Insights: Oncology this January, the authors re-confirm the original data reported by Abern et al. and then discuss an ongoing trial of MVA-5T4 in combination with docetaxel and prednisone for the treatment of mCRPC. This trial (more details of which are available on the web site) is a multi-center, randomized study designed to compare treatment with MVA-5T4 and docetaxel and prednisone to docetaxel and prednisone alone. (Note, however, that this is not a double-blind trial, because men receiving just the docetaxel and prednisone are not receiving a “dummy” injection of saline as a placebo for the injection of MVA-5T4.)

It should also be noted that an earlier, small, randomized, Phase II trial designed to compare treatment of men with mCRPC with MVA-5T4 together with docetaxel + prednisone directly to treatment with docetaxel + prednisone was terminated after enrollment of just 11 patients.

It seems hard to know, at this point in time, what the real potential of a drug like MVA-5T4 is going to be in the treatment of prostate cancer. It does appear to have some activity, but whether it can show a really significant degree of clinical activity (alone or in combination with other drugs) in the treatment of men with mCRPC is still open to question. If it does have meaningful activity, it may well be that a drug like this would actually be better used much earlier in the treatment of men with progressive or potentially progressive prostate cancer, but demonstrating such an effect could require large, long, and very expensive Phase III trials that may not be viable because of the costs and the risks involved.

For additional information about the development of MVA-5T4 in the treatment of prostate and other forms of cancer, we refer patients to the web site of Oxford BioMedica, the developer of this investigational agent.

3 Responses

  1. Small correction: It’s not double-blind because it’s an open label study, so both patient and doctor know who is getting which medication. A study may be placebo controlled or controlled with a treatment of known efficacy and still be double-blinded.

  2. Dear Allen:

    Thank you. You are, of course, technically correct, but I think you may be making a distinction that would escape the understanding of the average patient.

  3. Democratic trials.

    When the whole world became a small thing thanks to comunnication and the Internet, why is there still no international register of patients with mCRPC. Why are all trials are not multi-center?

    I am a patient with mCRPC. I am facing many difficulties to enter in trials. Why do I want to enter into such a trial? Because in this events are the most advanced drugs against cancer.

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