Metastatic castration-resistant prostate cancer (mCRPC) remains lethal despite recent therapeutic advances. This phase 1, first-in-human study investigated prostate stem cell antigen (PSCA)-directed CAR T cells in men with mCRPC. The primary endpoints were safety and dose-limiting toxicities (DLTs). While DLTs (grade 3 cystitis) were observed, dose adjustments led to a regimen with no DLTs. Cytokine release syndrome (grade 1 or 2) occurred in some patients. Prostate-specific antigen (PSA) declines (>30%) and radiographic improvements were observed in a subset of patients. CAR T cell persistence was limited. These results warrant further studies to optimize dosing and combination strategies.

Tanya B. Dorff, M. Suzette Blanchard, Lauren N. Adkins, Laura Luebbert, Neena Leggett, Stephanie N. Shishido, Alan Macias, Marissa M. Del Real, Gaurav Dhapola, Colt Egelston, John P. Murad, Reginaldo Rosa, Jinny Paul, Ammar Chaudhry, Hripsime Martirosyan, Ethan Gerdts, Jamie R. Wagner, Tracey Stiller, Dileshni Tilakawardane, Sumanta Pal, Catalina Martinez, Robert E. Reiter, Lihua E. Budde, Massimo D'Apuzzo, Peter Kuhn, Lior Pachter, Stephen J. Forman, Saul J. Priceman