Re-treatment With 177Lu-PSMA-617 for the Treatment of Metastatic Castration-Resistant Prostate Cancer, RE-LuPSMA Trial

PRIMARY OBJECTIVE: I. To assess the treatment efficacy of re-challenge lutetium Lu 177 vipivotide tetraxetan (177Lu-PSMA-617) therapy (for a maximum of 6 additional cycles) in patients with metastatic castration-resistant prostate cancer (mCRPC) who had a favorable response to a prior regimen of 177Lu-PSMA-617 therapy. SECONDARY OBJECTIVES: I. To determine the safety of re-challenge 177Lu-PSMA-617 therapy by Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. II. To determine the rate of patients who have a prostate-specific antigen (PSA) response (defined as a PSA decline of ≥ 50% during re-challenge 177Lu-PSMA-617 therapy). III. To determine biochemical progression-free survival (PFS) according to Prostate Cancer Working Group 3 (PCWG3) guidelines. IV. To determine overall survival (OS) from the start (cycle 1 day 1) of the first regimen of 177Lu-PSMA-617 therapy. V. To determine OS from the end (day 1 of the final cycle) of the first regimen of 177Lu-PSMA-617 therapy. VI. To determine radiographic progression-free survival (rPFS) according to Response Evaluation Criteria in PSMA positron emission tomography (PET)/computed tomography (CT) (RECIP) criteria. VII. To determine the impact of re-challenge 177Lu-PSMA-617 therapy on bone pain level, health-related quality of life, and performance status (Eastern Cooperative Oncology Group \[ECOG\]) using established standardized questionnaires. EXPLORATORY OBJECTIVE: I. To determine the dosimetry in organs and tumor lesions of re-challenge 177Lu-PSMA-617 therapy using a 24-hour single-time-point dosimetry protocol. OUTLINE: Patients receive 177Lu-PSMA-617 intravenously (IV) on day 1 of each cycle. Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive gallium Ga 68 gozetotide IV and undergo PET/CT at screening and on study, undergo single photon emission computed tomography (SPECT)/CT on study, and undergo collection of blood samples throughout the trial. After completion of study treatment, patients are followed up within 8 weeks of their last treatment cycle and then every 3 months for up to a total of 2 years.