Phase I/II trial of pembrolizumab and androgen-receptor pathway inhibitor with or without 225Ac-J591 for progressive metastatic castration resistant prostate cancer

The main purpose of this study is to evaluate the maximum tolerated and recommended dose of pembrolizumab and an androgen-receptor pathway inhibitor with or without 225Ac-J591, to see what the side effects are and if they work for metastatic castration resistant prostate cancer. Pembrolizumab may help the body’s immune system fight tumor cells. It does this by keeping certain blood cells, called T cells, active so they can attack the cancer. T-cells are also part of your immune system. Thousands of patients have received pembrolizumab, but it is not approved for most patients with prostate cancer. Hormonal drugs called androgen-receptor signaling inhibitors, such as enzalutamide are approved for treatment of advanced prostate cancer. Experimental studies suggest that they may also enhance the patients’ immune antitumor response, which is why they are being used in combination with immunotherapy in this study. Prostate-specific membrane antigen (PSMA) is a protein that is on the surface of most prostate cancer cells. It is absent from most other normal places in the body, but is present to a lower degree in the kidney, small intestine, salivary glands, and brain. J591 is a monoclonal antibody (an engineered protein) which recognizes PSMA. Actinium-225 (225Ac) is a small radioactive particle that emits alpha-particles (damaging/ionizing radiation).

Are you Eligible? (Inclusion Criteria)

• Male participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of prostate adenocarcinoma. 2. A male participant must agree to use a contraception during the treatment period and for at least 4 months after the last dose of study treatment and refrain from donating sperm during this period. 3. Ability to understand and the willingness to sign a written informed consent document.