eligibility_summary
Include: LA/mUC with measurable disease, no prior systemic tx for LA/mUC (adjuvant/neoadjuvant if relapse >12 mo), cis/carboplatin-eligible, HER2 IHC ≥1+, tissue or new biopsy, ECOG 0–2. Exclude: hypersensitivity to study drugs, prior serious PD-(L)1 irAEs, active/untreated CNS/leptomeningeal mets (treated, stable allowed), autoimmune disease needing systemic tx in 2y, prior T‑cell agents/transplant, symptomatic effusions/ascites, life expectancy <12 wks, prior MMAE or anti‑HER2.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 3, open-label RCT in previously untreated HER2-expressing (IHC ≥1+) locally advanced/metastatic urothelial carcinoma. Experimental: disitamab vedotin (RC48), an anti-HER2 antibody-drug conjugate delivering MMAE (microtubule inhibitor), plus pembrolizumab, an anti-PD-1 monoclonal antibody. Comparator: gemcitabine (antimetabolite nucleoside analog) with cisplatin or carboplatin (platinum DNA crosslinkers). Mechanisms/targets: disitamab vedotin binds HER2 on tumor cells → internalization and MMAE-mediated microtubule disruption, may also induce ADCC/bystander killing. Pembrolizumab blocks PD-1 on T cells, restoring anti-tumor immunity. Chemotherapy targets DNA synthesis/repair. Cells/pathways: HER2+ UC cells, microtubules, PD-1/PD-L1 axis, effector T cells, DNA replication/repair.