Levels of circulating tumor cells and of prostate specific antigen (PSA) were reduced by a new drug in patients who had already failed previous chemotherapy and hormone treatments. The new drug is an antibody-drug conjugate that consists of a monoclonal antibody targeting prostate-specific membrane antigen (PSMA) that is linked to monomethyl auristatin E (MMAE), which is a cancer-killing drug that disrupts tubules. The PSMA antibody drug conjugate (ADC) binds the PSMA on the surface of the prostate cancer cell and is absorbed into the cell were the MMAE is released, causing cell cycle arrest and cell death.

Once prostate cancer has spread to other parts of the body and has failed to respond to therapies blocking the male hormone androgen, few available treatment options exist. Usually, patients with advanced, hormone-refractory prostate cancer die from the disease after 12 to 18 months, so new therapies are desperately needed.

This phase I study enrolled 50 patients with the most advanced form of prostate cancer. Their cancer had spread to the bone and other organs, they had failed hormone therapy, and they had received up to two previous chemotherapies. The patients were treated with PSMA-ADC at levels ranging from 0.4 to 2.8 mg/kg by intravenous infusion over a period of 3 weeks per cycle, for up to four treatment cycles.

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The patients treated at the higher doses had detectable anti-tumor activity. About half the patients who received 1.8 mg/kg or higher had PSA levels reduced by 50% or more, circulating tumor cells in the blood fall to less than five cells per 7.5 mL of blood, or both.

The drug was generally well tolerated, though neutropenia occurred at the highest dose of 2.8 mg/kg, and one patient died. The cause of his death was unclear.

“These results show that PSMA ADC has anti-tumour activity in patients who have failed up to two prior chemotherapies and hormone therapy. We have initiated a phase II trial of up to 75 patients in which the recommended dose will be 2.5 mg/kg. This new trial will evaluate responses in PSA and CTC; it will evaluate control of metastases in bone, internal organs and lymph nodes; and it will look at the effect on pain. Safety also will be assessed. The fact that this new targeted therapy is active against the most advanced forms of prostate cancer is encouraging, as few or no therapeutic options are available at present,” said study leader Daniel Petrylak, MD, of Yale University Medical Center.

The results were presented at the 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Dublin, Ireland.