eligibility_summary
Eligibility: mCRPC adenocarcinoma (no small-cell/neuroendocrine), prior NAAD, on ADT/orchiectomy with castrate T, cohort-defined taxane history, PSMA PET-positive metastasis, PCWG3 progression (PSA>=2 or imaging/bone), ECOG 0-1, adequate marrow/liver/renal, eGFR & CrCl >60. Exclude: large PSMA-negative lesions, systemic therapy <4 wks, prior Ac-225, radiopharm limits (Group C needs prior 177Lu-PSMA), recent RT <6 wks, unstable >=G2 AEs, expansion: >3/diffuse/PSMA-non-avid liver mets.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Intervention: Actinium-225–macropa–pelgifatamab (BAY3546828, 225Ac‑pelgi), a PSMA-targeted radioimmunoconjugate/targeted alpha therapy (radiopharmaceutical). Mechanism: pelgifatamab is an anti‑PSMA monoclonal antibody, macropa chelates the alpha-emitter 225Ac. Upon binding PSMA on tumor cells, 225Ac delivers short‑range, high‑LET alpha radiation that induces lethal DNA double‑strand breaks, leading to tumor cell death with limited off‑target range. Dosing: IV every 6 weeks in Phase 1 dose escalation/expansion. Targets: PSMA (FOLH1) on prostate cancer cells in mCRPC (soft tissue and bone metastases). Affected pathways: DNA damage response/repair exhaustion and apoptosis from alpha radiation. Cohorts include patients with/without prior taxanes and a cohort after 177Lu‑PSMA therapy.