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

Sponsor
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Study ID
NCT07717242
Phase
PHASE2
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Disitamab vedotin — DRUG
    Disitamab vedotin, a HER2-targeted antibody-drug conjugate, will be administered intravenously at 2 mg/kg on Day 1 of each 2-week cycle (Q2W). During the neoadjuvant phase, participants will receive 6 cycles in combination with toripalimab and the arm-specific sensitizing agent. Participants who achieve clinical complete response after cTURBT and comprehensive response assessment will receive an additional 6 cycles of disitamab vedotin plus toripalimab as consolidation therapy.
  • Toripalimab — DRUG
    Toripalimab, an anti-PD-1 monoclonal antibody, will be administered intravenously at 3 mg/kg on Day 1 of each 2-week cycle (Q2W). During the neoadjuvant phase, participants will receive 6 cycles in combination with disitamab vedotin and the arm-specific sensitizing agent. Participants who achieve clinical complete response after cTURBT will receive 6 additional cycles of toripalimab plus disitamab vedotin consolidation therapy, followed by toripalimab maintenance therapy at 240 mg intravenously every 3 weeks (Q3W) for up to 1 year or until recurrence or study withdrawal.
  • Sitagliptin — DRUG
    Sitagliptin phosphate, a DPP-4 inhibitor, will be administered orally at 100 mg once daily throughout the 6-cycle neoadjuvant treatment phase (approximately 3 months), in combination with disitamab vedotin and toripalimab.
  • Zeprumetostat — DRUG
    Zeprumetostat, an EZH2 inhibitor, will be administered orally at 350 mg twice daily throughout the 6-cycle neoadjuvant treatment phase (approximately 3 months), in combination with disitamab vedotin and toripalimab.
  • Tafolecimab — DRUG
    Tafolecimab, a PCSK9-targeting monoclonal antibody, will be administered by subcutaneous injection at 150 mg on Day 1 of each 2-week cycle (Q2W) for 6 neoadjuvant treatment cycles (approximately 3 months), in combination with disitamab vedotin and toripalimab.
  • Ursodeoxycholic Acid — DRUG
    Ursodeoxycholic acid will be administered orally at 250 mg twice daily throughout the 6-cycle neoadjuvant treatment phase (approximately 3 months), in combination with disitamab vedotin and toripalimab.
  • Complete transurethral resection of bladder tumor — PROCEDURE
    Complete transurethral resection of bladder tumor (cTURBT) will be performed within 6 weeks after completion of 6 cycles of neoadjuvant therapy in all study arms. The procedure will be combined with imaging assessment, pathological evaluation, and urine cytology to determine clinical response, including clinical complete response, and to guide subsequent bladder-preservation management or salvage radical cystectomy.

Study Details

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.

Key Dates

First listed
Jul 21, 2026
Start date
Jul 1, 2026
Status verified
Jun 2026
Primary completion
Jun 30, 2028
Completion
Jan 31, 2029

Study Design

Enrollment
80 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Disitamab Vedotin + Toripalimab + Sitagliptin (Arm A)
    Participants will receive neoadjuvant disitamab vedotin (2 mg/kg every 2 weeks) plus toripalimab (3 mg/kg every 2 weeks) in combination with oral sitagliptin (100 mg once daily) for 6 cycles. Within 6 weeks after completion of neoadjuvant therapy, participants will undergo complete transurethral resection of bladder tumor (cTURBT) and comprehensive clinical response assessment using imaging, pathology, and urine cytology. Participants with clinical complete response (cCR) will receive 6 additional cycles of disitamab vedotin plus toripalimab, followed by toripalimab maintenance therapy (240 mg every 3 weeks) for up to 1 year. Participants without cCR will proceed to salvage treatment, including radical cystectomy when clinically indicated.
  • Experimental: Disitamab Vedotin + Toripalimab + Zeprumetostat (Arm B)
    Participants will receive neoadjuvant disitamab vedotin (2 mg/kg every 2 weeks) plus toripalimab (3 mg/kg every 2 weeks) in combination with oral zeprumetostat (350 mg twice daily) for 6 cycles. Within 6 weeks after completion of neoadjuvant therapy, participants will undergo cTURBT and comprehensive clinical response assessment using imaging, pathology, and urine cytology. Participants with cCR will receive 6 additional cycles of disitamab vedotin plus toripalimab, followed by toripalimab maintenance therapy (240 mg every 3 weeks) for up to 1 year. Participants without cCR will proceed to salvage treatment, including radical cystectomy when clinically indicated.
  • Experimental: Disitamab Vedotin + Toripalimab + Tafolecimab (Arm C)
    Participants will receive neoadjuvant disitamab vedotin (2 mg/kg every 2 weeks) plus toripalimab (3 mg/kg every 2 weeks) in combination with subcutaneous tafolecimab (150 mg every 2 weeks) for 6 cycles. Within 6 weeks after completion of neoadjuvant therapy, participants will undergo cTURBT and comprehensive clinical response assessment using imaging, pathology, and urine cytology. Participants with cCR will receive 6 additional cycles of disitamab vedotin plus toripalimab, followed by toripalimab maintenance therapy (240 mg every 3 weeks) for up to 1 year. Participants without cCR will proceed to salvage treatment, including radical cystectomy when clinically indicated.
  • Experimental: Disitamab Vedotin + Toripalimab + Ursodeoxycholic Acid (Arm D)
    Participants will receive neoadjuvant disitamab vedotin (2 mg/kg every 2 weeks) plus toripalimab (3 mg/kg every 2 weeks) in combination with oral ursodeoxycholic acid (250 mg twice daily) for 6 cycles. Within 6 weeks after completion of neoadjuvant therapy, participants will undergo cTURBT and comprehensive clinical response assessment using imaging, pathology, and urine cytology. Participants with cCR will receive 6 additional cycles of disitamab vedotin plus toripalimab, followed by toripalimab maintenance therapy (240 mg every 3 weeks) for up to 1 year. Participants without cCR will proceed to salvage treatment, including radical cystectomy when clinically indicated.

Primary Outcome Measure

Clinical Complete Response Rate [ Time Frame: At completion of 6 cycles of neoadjuvant therapy and cTURBT assessment, approximately 18 weeks after enrollment. ]

Central Contacts

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