eligibility_summary
Inclusion: Men ≥18 with histologically confirmed prostate cancer, on LHRH if no orchiectomy, prior regimen per cohort, mCRPC: progression and testosterone ≤50 ng/dL, mCSPC combos: high-volume mets, adequate counts, ≥1 PSMA+ lesion and no measurable PSMA−. Exclusion: recent anticancer therapy, >1 prior taxane (some cohorts), prior ARPI/chemo as specified, chronic steroids >10 mg, symptomatic CNS mets, malignancy ≤2 y, QTc >480 ms, ILD/pneumonitis, ocular disease, neuropathy ≥G2, seizure risk (apalutamide), proteinuria >1 g/24 h.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 1 FIH study in metastatic prostate cancer evaluating: 1) ARX517, an antibody–drug conjugate (ADC) composed of a humanized IgG1κ anti‑PSMA monoclonal antibody linked to two AS269 microtubule‑disrupting payloads. Mechanism: binds PSMA on prostate cancer cells, internalizes, releases cytotoxic payload to disrupt microtubules, causing mitotic arrest and cell death. 2) Combinations with androgen‑receptor pathway inhibitors: apalutamide (oral small‑molecule nonsteroidal AR antagonist) or abiraterone acetate plus prednisone (abiraterone is an oral small‑molecule CYP17A1 inhibitor that suppresses androgen biosynthesis, prednisone is a glucocorticoid co‑therapy). Targets: PSMA‑positive tumor cells, microtubules, androgen receptor signaling, androgen synthesis (CYP17 pathway). Goal: safety, PK/PD, MTD/RDD, preliminary efficacy.