Radioligand Therapy After PSMA PET Guided External Beam Radiotherapy for Treating Post-Prostatectomy Patients With Biochemically Recurrent Prostate Cancer

PRIMARY OBJECTIVES: I. Demonstrate the safety and feasibility of treating radiotherapy (RT) prostate cancer patients via addition of lutetium Lu 177 PSMA-10.1 (177Lu-rhPSMA-10.1) in a selected post-prostatectomy population. II. Analyze dosimetry of radioligand therapy (RLT) after each cycle of 177Lu-rhPSMA-10.1. EXPLORATORY OBJECTIVE: I. Determine the feasibility of and develop preliminary data in the correlation of circulating tumor circulating tumor deoxyribonucleic acid (ctDNA) at baseline, after RT, and RLT. OUTLINE: This is a dose-escalation study of 177Lu-rhPSMA-10.1. Patients undergo external beam radiation therapy (EBRT) followed by 177Lu-rhPSMA-10.1 intravenously (IV) on study. Patients also receive flotufolastat F-18 (rhPSMA-7.3) IV with positron emission tomography (PET)/computed tomography (CT) at screening and undergo single-photon emission computed tomography (SPECT)-CT and collection of blood samples on study. Patients follow up 6 weeks after the last 177Lu-rhPSMA-10.1 administration.