eligibility_summary
Eligible: adults ≥18 with first MIBC, predominant urothelial (≥50%), non‑metastatic (N0M0) by imaging, TURBT ≤90 d, ECOG 0–1, adequate organs. Exclude: diffuse CIS, extravesical UC, small‑cell/neuroendocrine, other active cancer, bladder dysfunction, prior pelvic RT/antineoplastics for MIBC or PD‑1/CTLA‑4/MMAE‑ADC, recent live vaccine/trial, immunodeficiency/immunosuppression, active autoimmune disease, pneumonitis, HIV/HBV/HCV infection, recent major CV events.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 2, single-arm bladder-preservation trial in MIBC tests induction pembrolizumab (MK-3475, anti–PD-1 IgG4 monoclonal antibody checkpoint inhibitor) plus enfortumab vedotin (ASG-22CE, Nectin-4–targeted antibody–drug conjugate carrying MMAE), followed by bladder 3D-CRT radiotherapy with continued pembrolizumab after maximal TURBT. Mechanisms: pembrolizumab blocks PD-1 on T cells to restore antitumor cytotoxicity, enfortumab vedotin binds Nectin-4 on urothelial tumor cells, is internalized, and releases MMAE to disrupt microtubules and induce apoptosis, radiotherapy causes local DNA damage and immunogenic cell death, potentially synergizing with checkpoint blockade. Targets/pathways: PD-1/PD-L1 axis on tumor-reactive T cells, Nectin-4–positive tumor cells and microtubule machinery, radiation-induced DNA damage/antigen release in the bladder.