VISION: an International, Prospective, Open-Label, Multicenter, Randomized Phase 3 Study of 177Lu-Psma-617 in the Treatment of Patients with Progressive PSMA-positive Metastatic Castration-Resistant Prostate Cancer (Mcrpc).

TPS5099 Background: The novel therapeutic drug 177Lu-PSMA-617 is a prostate specific membrane antigen (PSMA) targeting agent to deliver radionuclide therapy for the treatment of pts with metastatic castration resistant prostate cancer. Based on preclinical data that demonstrated high PSMA binding affinity & compound internalization, prolonged tumor uptake, rapid kidney clearance, & high tumor-to-background ratio, 177Lu-PSMA-617 proceeded into clinical development. Preliminary clinical evidence indicates 177Lu-PSMA-617 may demonstrate clinical benefit in pts with mCRPC in a setting where pts had no recommended standard of care. This Phase 3 study will assess the efficacy of 177Lu-PSMA-617 in patients with progressive PSMA-positive mCRPC by measuring overall survival (OS) and radiographic progression free survival (rPFS) in a randomized, prospective, open-label trial. Methods: The primary objective of this study is to compare the 2 alternative endpoints of rPFS & OS in pts with progressive PSMA-positive mCRPC who receive 177Lu-PSMA-617 in addition to best supportive/standard of care vs pts treated with best supportive/best standard of care alone. Eligibility criteria are: PSMA expressing tumor; prior exposure to a taxane and novel androgen axis drug. Pts will be randomized in a 2:1 ratio in favor of the investigational arm with stratification factors of LDH, liver disease, ECOG score, and use of NAAD at time of randomization as a standard of care. Under the alternative hypothesis, median OS on active is assumed to be 13.7 mo for a HR of 0.7306 and rPFS on the active is assumed to be 6 mo for a HR of 0.67. Planned enrollment for this study is 750 patients. Enrollment began in June 2018 and continues; the IDMC last reviewed the trial for safety in January 2019 and suggested that the trial continue as planned. Clinical trial information: NCT03511664.