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Bladder Urothelial CarcinomaPhase 2SYSTEMNCT07717242

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

A Phase 2 study testing Disitamab vedotin, Toripalimab and Sitagliptin in people with Bladder Urothelial Carcinoma and Bladder Cancer, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Bladder Urothelial Carcinoma, Bladder Cancer
What is being tested?
Disitamab vedotin, Toripalimab and Sitagliptin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
1 siteChina
Study dates
1 Jul 2026to 31 Jan 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • Adequate organ function, as determined by the following screening laboratory values obtained within 14 days before enrollment:
  • 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).
  • Total serum bilirubin ≤1.5 × ULN. For participants with Gilbert syndrome or indirect bilirubin elevation of extrahepatic origin, total bilirubin must be ≤3 × ULN.
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤2.5 × ULN.
  • 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.

Who cannot join

  • 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.
Show all 31Show fewer
  • Major surgery or major trauma within 28 days before enrollment. Placement of a vascular access device and TURBT are not considered major surgery.
  • Severe chronic or active infection requiring systemic antibacterial, antifungal, or antiviral treatment within 14 days before enrollment. HBV infection will be assessed according to Exclusion Criterion 13.
  • 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.
  • For Arm D, any of the following:
  • Acute cholecystitis or cholangitis.
  • Biliary obstruction.
  • Recurrent biliary colic attacks.
  • Radiopaque calcified gallstones.
  • Impaired gallbladder function.
  • Nonvisualization of the gallbladder on radiography.
  • Untreated chronic hepatitis B or hepatitis B virus carrier status with HBV DNA ≥500 IU/mL (2500 copies/mL). Participants with inactive hepatitis B surface antigen carrier status or stable active HBV infection after continuous antiviral therapy, with HBV DNA <500 IU/mL, may be enrolled. HBV DNA testing is required only for participants positive for hepatitis B core antibody.
  • Active hepatitis C. Participants with negative HCV antibody results, or participants with positive HCV antibody results but negative HCV RNA results during screening, may be enrolled. HCV RNA testing is required only for participants with positive HCV antibody results.
  • History of immunodeficiency, including positive human immunodeficiency virus (HIV) testing, other acquired or congenital immunodeficiency disorders, prior allogeneic stem cell transplantation, or prior organ transplantation.
  • Known allergy to other monoclonal antibodies.
  • Known allergy to any study drug or excipient.
  • Toxicities from any prior treatment that have not recovered to baseline or a stable level, unless the investigator determines that such toxicities are unlikely to pose a safety risk, for example alopecia, neuropathy, or specific laboratory abnormalities.
  • Any underlying medical condition, alcohol or drug abuse, or dependence that may interfere with study drug administration, affect interpretation of study results, or place the participant at high risk of treatment complications.
  • Concurrent participation in another interventional clinical study.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Wenlong Zhong, Professor contact

020-34078960

zhongwlong3@mail.sysu.edu.cn

Mingli Luo, Doctor contact

luomli5@mail.sysu.edu.cn

China1 site, 1 recruiting

  • Sun Yat-sen Memorial Hospital

    Guangzhou, Guangdong, 510000

    Tianxin Lin, Professor

    Recruiting

Other trials in China

About this study

Official title: Study on Immunotherapy Enhancement Strategies for 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.

Read more

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.

Read the detailed description

This is a Phase II, open-label, four-arm parallel study evaluating the efficacy and safety of sensitizing agents (sitagliptin, tazemetostat, tafolecimab, or ursodeoxycholic acid) combined with disitamab vedotin and toripalimab in patients with HER2-positive muscle-invasive urothelial carcinoma of the bladder (MIBC).

Disitamab vedotin, a HER2-targeted antibody-drug conjugate, combined with the PD-1 inhibitor toripalimab has shown promising anti-tumor activity in HER2-positive MIBC and may provide an opportunity for bladder preservation in selected patients. However, some patients remain insensitive or resistant to this treatment strategy and fail to achieve a clinical complete response. How to improve treatment sensitivity and enhance the efficacy of HER2-targeted and immune-based combination therapy remains an important clinical problem.

Preclinical studies from our center suggest that sitagliptin, tazemetostat, tafolecimab, and ursodeoxycholic acid may play a potentially important role in regulating the tumor immune microenvironment, inhibiting tumor growth, and enhancing the efficacy of PD-1 inhibitor-based treatment.

Based on these preclinical studies, the investigators designed this study to enroll patients with HER2-positive cT2-4aN0M0 MIBC and to explore, at the clinical level, the efficacy and safety of one sensitizing agent-sitagliptin, tazemetostat, tafolecimab, or ursodeoxycholic acid-combined with disitamab vedotin plus toripalimab, providing new combination treatment strategies for bladder preservation in patients with HER2-positive MIBC.

Being tested
Disitamab vedotin, Toripalimab, Sitagliptin, Zeprumetostat, Tafolecimab
Keywords
Urothelial Carcinoma, Bladder Cancer, Bladder Preservation Therapy, Disitamab Vedotin, Toripalimab, RC48
Medical subject headings
Urinary Bladder Neoplasms, Carcinoma, Transitional Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Disitamab vedotinDrug

    Also called RC48

    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.

  • ToripalimabDrug

    Also called JS001

    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.

  • SitagliptinDrug

    Also called Sitagliptin phosphate

    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.

  • ZeprumetostatDrug

    Also called SHR2554

    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.

  • TafolecimabDrug

    Also called IBI306

    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 AcidDrug

    Also called UDCA

    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 tumorProcedure or surgery

    Also called cTURBT

    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 groups in NCT07717242
Study groupRoleWhat they receive
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.
Receives: Drug: Disitamab vedotin; Drug: Toripalimab; Drug: Sitagliptin; Procedure: Complete transurethral resection of bladder tumor
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.
Receives: Drug: Disitamab vedotin; Drug: Toripalimab; Drug: Zeprumetostat; Procedure: Complete transurethral resection of bladder tumor
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.
Receives: Drug: Disitamab vedotin; Drug: Toripalimab; Drug: Tafolecimab; Procedure: Complete transurethral resection of bladder tumor
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.
Receives: Drug: Disitamab vedotin; Drug: Toripalimab; Drug: Ursodeoxycholic Acid; Procedure: Complete transurethral resection of bladder tumor

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: At completion of 6 cycles of neoadjuvant therapy and cTURBT assessment, approximately 18 weeks after enrollment.

Secondary outcomes (7)

  1. Overall Survival

    Overall survival (OS) is defined as the time from enrollment to death from any cause. Participants who are alive at the time of analysis will be censored at the date of last known follow-up.

    Measured: From enrollment through 5 years.

  2. Bladder-Intact Disease-Free Survival

    Bladder-intact disease-free survival (BI-DFS) is defined as the time from enrollment to the first occurrence of intravesical recurrence, regional lymph node recurrence, distant metastasis, salvage radical cystectomy, or death from any cause, as assessed by imaging, urine cytology, and cystoscopy.

    Measured: From enrollment through 5 years.

  3. Bladder Preservation Rate at 1, 3, and 5 Years

    Bladder preservation rate is defined as the proportion of participants who remain free from radical cystectomy and retain an intact, functioning bladder at 1, 3, and 5 years after enrollment.

    Measured: At 1, 3, and 5 years after enrollment.

  4. Partial Response Rate

    Partial response (PR) rate is defined as the proportion of participants who, after completion of 6 cycles of neoadjuvant treatment, have a reduction of at least 30% in the sum of diameters of target lesions on imaging, with residual disease no deeper than pT1 confirmed by cystoscopy and/or cTURBT biopsy, and no evidence of locally advanced or metastatic disease. Participants achieving clinical complete response are not included in the partial response rate.

    Measured: At completion of 6 cycles of neoadjuvant therapy and cTURBT assessment, approximately 18 weeks after enrollment.

  5. Change in Quality of Life Assessed by EORTC QLQ-C30

    Quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Changes in global health status, functional scales, and symptom scales from baseline will be evaluated over time. Higher scores on the global health status and functional scales indicate better quality of life, whereas higher scores on symptom scales indicate greater symptom burden.

    Measured: From baseline through 5 years after cTURBT.

  6. Total Direct Medical Cost

    Total direct medical cost is defined as the cumulative pre-reimbursement medical cost incurred from enrollment through the last follow-up visit. Costs include inpatient and outpatient costs, surgical costs, study treatment and concomitant medication costs, supportive care costs, laboratory and imaging examination costs, pathological examination costs, radiotherapy-related costs, and other medically related costs.

    Measured: From enrollment through 5 years.

  7. Incidence Rate of Adverse Events

    The incidence rate of adverse events (AEs) is defined as the percentage of participants who experience at least one AE after initiation of study treatment. The numerator is the number of participants with at least one AE, and the denominator is the number of participants in the safety analysis set. AEs will be coded and summarized by type, severity, seriousness, and relationship to study treatment. Drug-related AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0).

    Measured: From first study treatment through 90 days after the last study treatment, up to approximately 18 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jul 2026
  2. Study start1 Jul 2026 (estimated)
  3. Primary completion30 Jun 2028 (estimated)
  4. Study completion31 Jan 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
80 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07717242
Sponsor's protocol ID
SYSKY-2026-461-02
Other IDs
2024ZD0525700
Acronym
SYSTEM
Status last verified
Jun 2026
First submitted
6 Jul 2026
Last updated
21 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Disitamab vedotin, Toripalimab and Sitagliptin in people with Bladder Urothelial Carcinoma and Bladder Cancer, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 21 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Wenlong Zhong, Professor (020-34078960, zhongwlong3@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07717242.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2026.

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