Sun Yat-Sen Treatment Strategy for Enhancing Response in Muscle-invasive Bladder Cancer

This is a multicenter, prospective, open-label, Phase II, four-arm parallel study evaluating the efficacy and safety of different sensitization strategies combined with disitamab vedotin and toripalimab in patients with HER2-positive muscle-invasive urothelial carcinoma of the bladder (MIBC). Eligible patients with cT2-4aN0M0 HER2-positive urothelial carcinoma of the bladder will receive neoadjuvant disitamab vedotin plus toripalimab in combination with one of four sensitizing agents: sitagliptin, tazemetostat, tafolecimab, or ursodeoxycholic acid. After six cycles of neoadjuvant treatment, patients will undergo comprehensive response assessment, including imaging, cystoscopy, urine cytology, and complete transurethral resection of bladder tumor (cTURBT). Patients who achieve a clinical complete response (cCR) may enter a bladder-preservation treatment pathway, including additional disitamab vedotin plus toripalimab and subsequent toripalimab maintenance therapy. Patients who do not achieve cCR will be considered for salvage radical cystectomy. The primary objective is to evaluate the cCR rate of each treatment strategy. Secondary objectives include bladder-intact disease-free survival, overall survival, bladder preservation rate, safety, quality of life, treatment costs, and exploratory biomarker analyses.

NCT Number	NCT07717242
Lead Sponsor	Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University Collaborators: First Affiliated Hospital of Chongqing Medical University, Tianjin Medical University Second Hospital, Peking University First Hospital, Peking University People's Hospital, The First Affiliated Hospital with Nanjing Medical University, Shengjing Hospital, Fujian Provincial Hospital Affiliated to Fuzhou University
Conditions	Bladder Urothelial Carcinoma, Bladder Cancer
Enrollment	80 participants
Start Date	2026-07-01
Primary Completion	2028-06-30 (estimated)
Study Completion	2029-01-31 (estimated)
Updated on ClinicalTrials.gov	2026-07-21