PSMA-ADC shows positive results in Phase I clinical trial in advanced mCRPC

According to data presented today at the Symposium on Molecular Targets and Cancer Therapeutics in Dublin, Ireland, a new type of targeted drug therapy has shown early positive results in men with metastatic, castration-resistant porstate cancer (mCRPC) who had also failed at least two forms of chemotherapy.

A media release from the European Cancer Organization (ECCO) states that the new form of therapy directly targets prostate cancer cells carrying a molecule known as prostate-specific membrane antigen or PSMA. The drug does this by combining a targeting agent (a PSMA monoclonal antiobody) and a cancer cell-killing agent called monomethyl auristatin E (MMAE). MMAE disrupts tubulins — the molecules inside cancer cells that are essential for cell division.

We shall simply refer to this drug as PSMA-ADC, which stands for PSMA antibody-drug conjugate.

The media release is relatively light on specific data, but what we know at this time is the following:

  • A Phase I trial has been completed in 50 men at doses of PSMA-ADC between 0.4 and 2.8 mg/kg for four cylces of therapy with each cycle lasting 3 weeks.
  • Anti-tumor activity was observed in patients who were treated at the higher doses.
  • About 50 percent of patients treated with doses of ≥ 1.8 mg/kg showed 
    • A ≥ 50 percent reduction in PSA levels, or
    • A reduction in serum levels of circulating tumor cells (CTCs)  to less than five cells per 7.5 ml of blood, or
    • Both of the above
  • The drug was “generally well tolerated”, but
    • Neutropenia (low levels of white blood cells) was significant at the highest dose of the drug (2.8 mg/kg).
    • One patient died on the highest dose of the drug but “the cause of the death is unclear.”
  • A Phase II trial of PSMA-ADC in up to 75 patients has been initiated.
  • The dose of PSMA-ADC to be used in this Phase II trial will be 2.5 mg/kg.

There is no reference to the drug’s developer in the media release, but this certainly appears to be the compound under development in association with Progenics Pharmaceuticals, Inc. Clearly there is a considerable way to go before this compound is actually shown to have sufficient efficacy and safety for widespread use in the treatment of mCRPC.

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