Phase 1 trial of single-dose Lu-177 PSMA-617 followed by maintenance pembrolizumab for metastatic castration-resistant prostate cancer

Checkpoint inhibitors have only limited activity in patients with metastatic castration-resistant prostate cancer (mCRPC). A phase 1 trial at University of California San Francisco evaluated a single dose of lutetium-177 prostate-specific membrane antigen-617 (¹⁷⁷Lu-PSMA-617) followed by maintenance pembrolizumab in these patients. The trial showed that this treatment was safe (5% grade 3 or worse treatment-related adverse events, no treatment-related deaths) and had encouraging preliminary activity. The authors conclude that the study provides robust clinical support for the immunogenic effect of radiation and provides the impetus to further evaluate immune checkpoint inhibition in patients with mCRPC as a maintenance treatment followin primiang with targeted radioligand therapy.