eligibility_summary
Adults ≥18 with PSMA+ mCRPC, ECOG 0–1, >6‑mo survival, on ADT/orchiectomy with castrate T, prior AR‑targeted agent, ≤2 taxanes or unfit/refuse, PSA/RECIST/bone progression, ≥1 met lesion, adequate organs, contraception required. Exclude: unresolved ≥Gr2 AEs, recent/concurrent therapy or transfusion, PSMA‑negative bulky lesions, prior radioligand, unstable CNS/superscan/cord compression, serious comorbidity, other active malignancy, immunosuppression, active GI/autoimmune disease.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Trial NCT05682443 tests two agents in PSMA-positive mCRPC: 1) ONC‑392 (gotistobart), a humanized IgG1 anti‑CTLA‑4 monoclonal antibody (immune checkpoint inhibitor) that blocks CTLA‑4 to restore CD28/B7 costimulation, enhancing T‑cell priming/expansion and potentially depleting intratumoral regulatory T cells via Fc‑mediated cytotoxicity, 2) Lutetium Lu‑177 vipivotide tetraxetan (Pluvicto), a PSMA‑targeted radioligand (small‑molecule PSMA ligand chelated to β‑emitter Lu‑177) that binds PSMA on prostate cancer cells, is internalized, and delivers β‑radiation causing DNA double‑strand breaks and tumor death (with cross‑fire). Targets/pathways: CTLA‑4 on T cells (Tregs/effector T cells), APC B7/CD28 costimulation, PSMA on prostate tumor cells, and DNA damage pathways.