Study of the Safety and Efficacy of a New Radioactive Therapy (177Lu-rhPSMA-10.1) for Advanced Prostate Cancer

Prostate cancer is the most common cancer in men. Metastatic castration-resistant prostate cancer (mCRPC) is an advanced form of the disease in which the cancer has already spread to other organs and formed secondary tumors (metastases). “Castration-resistant” means that the tumor no longer responds to treatments that lower testosterone levels (anti-hormone therapies). Many prostate cancer cells carry a specific protein on their surface called prostate-specific membrane antigen (PSMA). Modern therapies use this characteristic to specifically target and combat cancer cells. This study investigates targeted radioligand therapy using the investigational drug 177Lu-rhPSMA-10.1, a drug complex consisting of a ligand and a radioactive isotope that is administered intravenously. The compound consists of a ligand (molecule) that specifically binds to PSMA and is linked to the radioactive substance lutetium-177. After injection into the bloodstream, the ligand binds to PSMA-expressing cancer cells and, through the radioactive substance attached to it, selectively emits radiation into the surrounding area to destroy these cells, while healthy tissue is largely spared.

The goal of the Phase 1 and Phase 2 study is to evaluate the drug 177Lu-rhPSMA-10.1 for safety, tolerability, and efficacy in the treatment of advanced prostate cancer (mCRPC). Before treatment, a special imaging test (PSMA PET/CT) is used to determine whether the tumor cells actually express PSMA. Participation is only considered if this is the case. The study is divided into two phases: In Phase 1, the safety and optimal dose of the drug will be evaluated in a small group of patients who have already been treated with modern anti-hormone therapies (such as abiraterone or enzalutamide) and one or two courses of chemotherapy (taxanes), but whose cancer has continued to progress. To this end, patients will be assigned to one of two groups in which different dosages of the drug will be tested (5.55 vs. 7.4 GBq). Patients will receive the respective drug intravenously for a maximum of three cycles. In Phase 2, the drug’s efficacy and safety will be further investigated in a larger group. Here, different dosing regimens will be compared based on the data from Phase 1. Eligible patients are those who have already received anti-hormone therapies but have not yet undergone chemotherapy for the treatment of prostate cancer. In Cohort 2A, patients initially receive two doses, each with an activity of 10.00 GBq. This is followed by up to five additional doses, each with an activity of 7.40 GBq, administered at six-week intervals. Patients in Cohort 2B will receive up to eight doses, each with an activity of 7.40 GBq. The treatment plan here differs in that it uses shorter intervals at the beginning: the first three doses are administered at three-week intervals, while the remaining doses follow at six-week intervals. Cohort 2C, which is optional, involves a treatment plan with the highest initial dose. Patients in this cohort initially receive two doses, each with an activity of 14.80 GBq. This is followed by up to four additional doses, each with an activity of 7.40 GBq. In this cohort as well, all doses are administered at six-week intervals. Patients are examined regularly to monitor side effects and assess treatment success (e.g., by measuring PSA levels).

Men aged 18 and older with mCRPC whose testosterone levels are permanently low due to castration (medicinal or surgical) are eligible to participate. The cancer must be progressive, and patients must not have any other serious medical conditions (e.g., severe kidney problems or other cancers). In addition, the tumor must not have metastasized to the central nervous system. An important requirement is that the tumor be PSMA-positive and that no significant portions of the tumor be PSMA-negative.