eligibility_summary
Eligible: ≥18, consent, treatment‑naïve very high‑risk prostate adenocarcinoma (Gleason ≥4+4 and cT3 plus cN+ or PSA>20), M0 on conventional imaging (≤oligometastatic on PSMA PET), ECOG 0–1, candidate for RP+PLND, PSMA PET SUVmax>12, adequate labs (hematologic/hepatic/renal/endocrine, albumin/electrolytes, enzymes, glucose<200), condom use, tissue available. Exclude: M1, PSA<20 without nodes, prior ADT/AR tx/orchiectomy/prostate therapy, recent investigational/surgery/immuno/radioligand, immunosuppression/transplant, other cancer, serious illness/infection, HIV/HBV/HCV, hypersensitivity, substance abuse, other trial, poor follow‑up, legal incapacity.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
NEPI Trial (NCT06388369): Phase I/II randomized, open-label neoadjuvant study in very high-risk, PSMA-PET–positive, nonmetastatic prostate cancer before prostatectomy. Interventions: [177Lu]Lu-PSMA-617 radioligand therapy (radiopharmaceutical, PSMA-617 small-molecule ligand chelated to lutetium-177 beta-emitter) with or without ipilimumab (immune checkpoint inhibitor, IgG1 monoclonal antibody against CTLA-4). Mechanisms: Lu-PSMA binds PSMA (FOLH1) on prostate cancer cells, is internalized, and delivers beta radiation causing DNA double-strand breaks and crossfire killing. Ipilimumab blocks CTLA-4 on T cells, reducing Treg-mediated suppression and enhancing effector T-cell priming/expansion. Targets/pathways: PSMA-expressing prostate tumor cells, DNA damage response, CTLA-4/T-cell activation axis and tumor immune microenvironment. All patients receive ADT (androgen receptor pathway suppression).