eligibility_summary
Eligibility: Men ≥18 with progressive mCRPC, castrate T<50 ng/dL, prior ≥1 next‑gen ARSI, PSMA PET–avid lesion, ECOG 0–1, adequate organs, recovered AEs, RT washout, contraception, biopsy feasible, treated, stable brain mets allowed. Exclude: de novo small cell, PSMA‑negative soft lesions, recent systemic/IO or PSMA‑directed therapy, >2 taxanes, active autoimmune/immunodef/steroids, pneumonitis, major CV disease, recent surgery/RT/infection, HBV/HCV unsuppressed, TB, HIV, bleeding risk, noncompliance.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Interventions: Pembrolizumab (Keytruda), an anti-PD-1 IgG4 monoclonal antibody immune checkpoint inhibitor (IV q6w), and 177Lu-PSMA-617 (radioligand therapy), a PSMA-targeted small molecule linked to the beta-emitter lutetium-177 that delivers localized radiation to PSMA-expressing tumors. Mechanisms: Pembrolizumab blocks PD-1 on T cells to restore antitumor activity. 177Lu-PSMA-617 binds PSMA on prostate cancer cells, is internalized, and emits beta particles causing DNA damage and tumor cell death, potentially increasing antigen release. Cells/pathways targeted: PD-1/PD-L1 axis on exhausted CD8+ T cells, PSMA on prostate cancer cells (PSMA-PET–avid lesions) and tumor neovasculature, tumor microenvironment, including effector T-cell and myeloid cell states.