eligibility_summary
Eligible: ECOG 0–1, muscle‑invasive bladder urothelial carcinoma (≥50% UC), cT2–T4a N0 M0, prior TURBT/partial cystectomy with tissue and IHC 2+/3+, planned radical cystectomy+LND+urinary diversion, life ≥3 mo, adequate marrow/liver/renal (CrCl>30), consent, WOCBP negative test. Exclude: prior PD‑1/PD‑L1/PD‑L2, recent therapy/trial, pregnancy/lactation, HIV, active HBV/HCV/TB, autoimmune disease, major/uncontrolled comorbidity, recent live vaccine/transplant/surgery, other cancers (limited exceptions), upper‑tract UC.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 2 single-arm trial in HER2-high muscle-invasive bladder cancer tests: 1) Disitamab vedotin (RC48), a HER2-targeted antibody-drug conjugate delivering MMAE (microtubule inhibitor) to HER2-expressing tumor cells, 2) Toripalimab, an anti–PD-1 monoclonal antibody immune checkpoint inhibitor, 3) Bladder radiotherapy (>50 Gy). Mechanisms: RC48 binds HER2 on urothelial carcinoma cells, is internalized, and releases MMAE to disrupt microtubules and kill tumor cells (with potential bystander effect). Toripalimab blocks PD-1 on T cells, restoring antitumor immunity and synergizing with radiation. Radiotherapy causes DNA damage and immunogenic cell death, increasing antigen release. Targets/pathways: HER2 on tumor cells, PD-1/PD-L1 axis on T cells, microtubules, DNA damage/immune activation pathways.