Sun Yat-Sen Treatment Strategy for Enhancing Response in Muscle-invasive Bladder Cancer
SYSTEM
Study on Immunotherapy Enhancement Strategies for Muscle-invasive Bladder Cancer
2 other identifiers
interventional
80
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jul 2026
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2026
CompletedFirst Submitted
Initial submission to the registry
July 6, 2026
CompletedFirst Posted
Study publicly available on registry
July 21, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 31, 2029
July 21, 2026
June 1, 2026
2 years
July 6, 2026
July 16, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Clinical Complete Response Rate
Clinical complete response (cCR) rate is defined as the proportion of participants who have no visible tumor on imaging, no evidence of malignancy on cystoscopy and/or complete transurethral resection of bladder tumor (cTURBT) biopsy, and negative urine cytology after completion of 6 cycles of neoadjuvant treatment. Clinical response will be determined by comprehensive assessment using imaging, pathology, cystoscopy/cTURBT findings, and urine cytology.
At completion of 6 cycles of neoadjuvant therapy and cTURBT assessment, approximately 18 weeks after enrollment.
Secondary Outcomes (7)
Overall Survival
From enrollment through 5 years.
Bladder-Intact Disease-Free Survival
From enrollment through 5 years.
Bladder Preservation Rate at 1, 3, and 5 Years
At 1, 3, and 5 years after enrollment.
Partial Response Rate
At completion of 6 cycles of neoadjuvant therapy and cTURBT assessment, approximately 18 weeks after enrollment.
Change in Quality of Life Assessed by EORTC QLQ-C30
From baseline through 5 years after cTURBT.
- +2 more secondary outcomes
Study Arms (4)
Disitamab Vedotin + Toripalimab + Sitagliptin (Arm A)
EXPERIMENTALParticipants 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.
Disitamab Vedotin + Toripalimab + Zeprumetostat (Arm B)
EXPERIMENTALParticipants 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.
Disitamab Vedotin + Toripalimab + Tafolecimab (Arm C)
EXPERIMENTALParticipants 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.
Disitamab Vedotin + Toripalimab + Ursodeoxycholic Acid (Arm D)
EXPERIMENTALParticipants 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.
Interventions
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, 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 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, 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, 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 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 (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.
Eligibility Criteria
You may qualify if:
- Voluntarily participate in this study, provide written informed consent, and be able to understand and agree to comply with the study requirements and assessment schedule.
- Age ≥18 years on the date of signing the informed consent form.
- Histologically confirmed and radiologically assessed cT2-T4aN0M0 urothelial carcinoma of the bladder according to the American Joint Committee on Cancer (AJCC) 8th edition TNM staging system. For tumors with mixed histology, urothelial carcinoma must be the predominant component (at least 50%).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- HER2 expression ≥1+ confirmed by immunohistochemistry using a pretreatment tumor specimen tested at a local laboratory.
- Availability of tumor tissue obtained from transurethral resection of bladder tumor (TURBT), together with the corresponding pathology report. Fresh surgical tissue or unstained pathology slides may be submitted.
- Adequate organ function, as determined by the following screening laboratory values obtained within 14 days before enrollment:
- a. For assessment of the following hematologic parameters, participants must not have received growth factor support within 14 days before sample collection: i. Absolute neutrophil count ≥1.5 × 10\^9/L; ii. Platelet count ≥90 × 10\^9/L; iii. Hemoglobin ≥90 g/L. b. International normalized ratio (INR) or activated partial thromboplastin time (aPTT) ≤1.5 × the upper limit of normal (ULN).
- c. Total serum bilirubin ≤1.5 × ULN. For participants with Gilbert syndrome or indirect bilirubin elevation of extrahepatic origin, total bilirubin must be ≤3 × ULN.
- d. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤2.5 × ULN.
- e. Pulmonary function indicating ability to tolerate surgery.
- Women who are not pregnant or women of childbearing potential must be willing to use highly effective contraception during the study and for at least 120 days after the last dose of disitamab vedotin or toripalimab, whichever occurs later, and must have a negative urine or serum pregnancy test within 7 days before enrollment. Non-sterilized male participants must be willing to use highly effective contraception during the study and for at least 120 days after the last dose of disitamab vedotin or toripalimab, whichever occurs later.
You may not qualify if:
- Prior treatment with therapies targeting PD-1, PD-L1, PD-L2, CTLA-4, LAG-3, HER2, or Nectin-4, or with other antibodies or drugs specifically targeting T-cell co-stimulatory or checkpoint pathways.
- Receipt of other approved systemic anticancer therapy or systemic immunomodulators, including but not limited to interferon, interleukin-2, or tumor necrosis factor, within 28 days before enrollment.
- Prior radiotherapy for bladder cancer.
- Prior antitumor drug therapy, except for the following:
- For participants who previously received systemic chemotherapy, a treatment-free interval of at least 12 months from the last treatment to the start of neoadjuvant study treatment is required.
- Local intravesical chemotherapy or immunotherapy must have been completed at least 1 week before the start of neoadjuvant study treatment.
- Major surgery or major trauma within 28 days before enrollment. Placement of a vascular access device and TURBT are not considered major surgery.
- Receipt of a live vaccine within 28 days before enrollment. Seasonal injectable influenza vaccines are generally inactivated and are permitted; intranasal vaccines are live vaccines and are not permitted.
- Active autoimmune disease requiring systemic treatment and considered by the investigator to affect study treatment.
- Requirement for long-term high-dose corticosteroids or other immunosuppressive agents considered by the investigator to affect study treatment.
- Any history of uncontrolled systemic disease that, in the investigator's judgment, may affect treatment, including abnormal potassium, sodium, or calcium levels; hypoalbuminemia; interstitial lung disease; noninfectious pneumonitis; diabetes mellitus; hypertension; cardiovascular disease; or other uncontrolled systemic disease.
- For Arm A, any of the following:
- Treatment with a DPP-4 inhibitor within 60 days before the first administration of study treatment.
- Diabetes mellitus requiring any glucose-lowering medication, including long-acting or short-acting insulin, DPP-4 inhibitors, GLP-1 receptor agonists, or other glucose-lowering drugs.
- Fasting blood glucose \<4 mmol/L.
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen Universitylead
- First Affiliated Hospital of Chongqing Medical Universitycollaborator
- Tianjin Medical University Second Hospitalcollaborator
- Peking University First Hospitalcollaborator
- Peking University People's Hospitalcollaborator
- The First Affiliated Hospital with Nanjing Medical Universitycollaborator
- Shengjing Hospitalcollaborator
- Fujian Provincial Hospital Affiliated to Fuzhou Universitycollaborator
Study Sites (1)
Sun Yat-sen Memorial Hospital
Guangzhou, Guangdong, 510000, China
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 6, 2026
First Posted
July 21, 2026
Study Start
July 1, 2026
Primary Completion (Estimated)
June 30, 2028
Study Completion (Estimated)
January 31, 2029
Last Updated
July 21, 2026
Record last verified: 2026-06
Data Sharing
- IPD Sharing
- Will not share