Phase I dose-escalation study of fractionated-dose 177Lu-PSMA-617 for progressive metastatic castration resistant prostate cancer (mCRPC).

TPS5093Background: PC is a radiosensitive disease. PSMA is selectively overexpressed in advanced PC with upregulation by androgen receptor (AR) pathway dysregulation; limited expression exists in other organs. A series of sequential studies of radiolabeled anti-PSMA antibody J591 revealed 1) targeting and safety [Bander 2003]; 2) safety and prelim efficacy [Milowsky 2004, Bander 2005]; 3) efficacy and initial dose-response [Tagawa 2013]; 4) dose-fractionation allows higher doses, ability to combine with docetaxel, confirmation of dose-response (PSA and overall survival) [ASCO 2010, 2014, 2016]; 5) predictable, reversible myelosuppression is dose-limiting [Tagawa 2013]. Small molecule PSMA inhibitor ligands can be successfully radiolabeled and are widely used for imaging and treatment in Europe. 177Lu-PSMA-617 is the most commonly used, but experience is mostly anecdotal/retrospective and no formal dose-escalation studies have been performed. Methods: Men with progressive mCRPC following at least 1 potent ...