Optimization of Prostate-Specific Membrane Antigen-Targeted Radiation

There are currently no curative therapies for men with advanced prostate cancer. However, promising recent studies have suggested that radiation-emitting therapies that target PSMA, a protein specifically expressed by prostate cancer cells, may be highly effective in men with advanced prostate cancer. Clinical trials are needed to validate efficacy and optimize the use of this type of treatment. Tagawa and team will conduct clinical trials testing several PSMA-targeting radiation therapies for the treatment of prostate cancer. A phase I clinical trial will be conducted to test 177Lu-PSMA-617, a PSMA-targeted small molecule that is attached to a beta particle-emitting radioactive molecule. This trial will determine safety and efficacy of this treatment as well as determine the optimal dose and schedule. Once safe doses of 177Lu-PSMA-617 have been established, the team will initiate a clinical trial testing increasing doses of 177Lu-PSMA-617 combined with 177Lu-J591, which is a PSMA-targeted antibody attached to a beta particle-emitting radioactive molecule. These agents will be given on alternating weeks. Tumor samples will be collected from the patients on these trials and studied to identify biomarkers that select patients most likely to benefit from 177Lu-labeled PSMA-targeting agents. In addition, a phase I/II clinical will be conducted to evaluate the safety and efficacy of 225Ac-J591, a PSMA-targeted antibody that is attached to an alpha particle-emitting radioactive molecule, in patients with mCRPC. If successful, this project will prioritize several PSMA-targeted radiation therapies according to safety and efficacy and result in a powerful new therapy that uses targeted radiation to eliminate prostate cancer. What this means to patients: Recent studies have suggested that PSMA-targeted radiation therapy may be highly effective in men with advanced prostate cancer, however controlled clinical trials have not yet been conducted for these agents. This team will test several PSMA-targeted radiation therapies in clinical trials and optimize the use of these powerful new treatments for prostate cancer.