Bladder-Sparing Treatment With Disitamab Vedotin and Toripalimab With or Without Pelvic Lymph Node Dissection in Bladder Cancer

A Prospective, Multicenter, Randomized Controlled Study of Disitamab Vedotin Plus Toripalimab With or Without Pelvic Lymph Node Dissection for Bladder-Sparing Treatment in Patients With cT2-3N0M0 Bladder Urothelial Carcinoma

This is a prospective, multicenter, randomized controlled superiority study designed to evaluate whether the addition of pelvic lymph node dissection improves bladder-intact event-free survival in patients with cT2-3N0M0 bladder urothelial carcinoma receiving bladder-sparing treatment. Eligible patients with HER2 expression of IHC 2+ or higher who decline radical cystectomy will be randomized 1:1 to receive maximal transurethral resection of bladder tumor followed by disitamab vedotin plus toripalimab with or without standardized pelvic lymph node dissection. The primary endpoint is the 2-year bladder-intact event-free survival rate. Secondary endpoints include clinical complete response, partial response, disease progression, overall survival, quality of life, safety, treatment cost, and exploratory biomarker analyses.

Study Overview

• Status: Not yet recruiting
• Conditions: Bladder Cancer; Muscle-invasive Bladder Cancer; Bladder Urothelial Carcinoma
• Intervention / Treatment: Drug: Disitamab Vedotin (RC48); Drug: Toripalimab; Procedure: Transurethral Resection of Bladder Tumor; Procedure: Pelvic Lymph Node Dissection

Detailed Description

Muscle-invasive bladder cancer is commonly treated with radical cystectomy; however, bladder-sparing strategies are needed for selected patients who decline cystectomy. This study evaluates a bladder-sparing strategy based on maximal transurethral resection of bladder tumor, disitamab vedotin plus toripalimab, and the addition of standardized pelvic lymph node dissection.

Participants will be randomized to receive disitamab vedotin plus toripalimab with or without pelvic lymph node dissection after maximal transurethral resection of bladder tumor. Tumor response will be assessed by imaging, cystoscopy or transurethral resection/biopsy when clinically indicated, and urine cytology. Participants who meet bladder-sparing criteria will enter bladder-intact follow-up according to the protocol. Safety, survival, quality of life, treatment cost, and exploratory biomarkers will also be evaluated.

• Study Type: Interventional
• Enrollment (Estimated): 114
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Hailong Hu; Phone Number: +86 13662096232; Email: huhailong@tmu.edu.cn
• Study Contact Backup: Name: Peng Li; Phone Number: +86 18935803489; Email: lipeng990220@tmu.edu.cn

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300211
      • The Second Hospital of Tianjin Medical University
      • Contact: Peng Li; Phone Number: +86 18935803489; Email: lipeng990220@tmu.edu.cn
      • Contact: Hailong Hu, MD,PhD; Phone Number: +86 13662096232; Email: huhailong@tmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female participants aged 18 years or older.
2. Histologically confirmed bladder urothelial carcinoma.
3. Clinical stage cT2-3N0M0 according to the AJCC 8th edition TNM staging system.
4. HER2 expression of IHC 2+ or higher.
5. Participants who decline radical cystectomy as assessed by the investigator.
6. Adequate organ function as defined in the study protocol.
7. Ability to understand and willingness to sign written informed consent.

Exclusion Criteria:

1. Known allergy or hypersensitivity to disitamab vedotin, toripalimab, their excipients, or other monoclonal antibodies.
2. Prior radiotherapy for bladder cancer.
3. Prior anticancer treatment that may affect efficacy assessment, as defined in the study protocol.
4. Pregnant or breastfeeding women.
5. Any serious uncontrolled disease or medical condition that, in the investigator's judgment, would make participation inappropriate.
6. Participation in another interventional clinical trial that may interfere with this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Disitamab Vedotin Plus Toripalimab With Pelvic Lymph Node Dissection; Participants will receive maximal transurethral resection of bladder tumor followed by disitamab vedotin plus toripalimab and standardized pelvic lymph node dissection.	Drug: Disitamab Vedotin (RC48); Disitamab vedotin will be administered in combination with toripalimab according to the study protocol.; Drug: Toripalimab; Toripalimab will be administered in combination with disitamab vedotin according to the study protocol.; Procedure: Transurethral Resection of Bladder Tumor; Maximal transurethral resection of bladder tumor will be performed as part of the bladder-sparing treatment strategy.; Procedure: Pelvic Lymph Node Dissection; Standardized pelvic lymph node dissection will be performed in participants assigned to the PLND arm.
Active Comparator: Disitamab Vedotin Plus Toripalimab Without Pelvic Lymph Node Dissection; Participants will receive maximal transurethral resection of bladder tumor followed by disitamab vedotin plus toripalimab without planned pelvic lymph node dissection.	Drug: Disitamab Vedotin (RC48); Disitamab vedotin will be administered in combination with toripalimab according to the study protocol.; Drug: Toripalimab; Toripalimab will be administered in combination with disitamab vedotin according to the study protocol.; Procedure: Transurethral Resection of Bladder Tumor; Maximal transurethral resection of bladder tumor will be performed as part of the bladder-sparing treatment strategy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year Bladder-intact Event-free Survival Rate	The proportion of participants who remain alive with an intact bladder and without muscle-invasive bladder cancer recurrence, regional lymph node recurrence, distant metastasis, radical cystectomy, or bladder cancer-related death at 24 months after randomization.	24 months after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Complete Response Rate	The proportion of participants who achieve clinical complete response, defined as no visible tumor on imaging, no evidence of malignancy on cystoscopy or TURBT/biopsy when clinically indicated, and negative urine cytology. For participants undergoing pelvic lymph node dissection, no lymph node metastasis is required.	After completion of induction treatment, up to 12 weeks
Partial Response Rate	The proportion of participants with non-muscle-invasive disease, including Ta, T1, or carcinoma in situ, confirmed by urine cytology or pathological biopsy, with no evidence of locally advanced or metastatic disease on imaging.	After completion of induction treatment, up to 12 weeks
Disease Progression Rate	The proportion of participants with disease progression, defined as muscle-invasive bladder cancer confirmed by pathological biopsy, locally advanced disease, regional lymph node recurrence, distant metastasis, or bladder cancer-related death.	Up to 24 months after randomization
Overall Survival	Overall survival is defined as the time from randomization to death from any cause.	Up to 60 months after randomization
Incidence and Severity of Adverse Events	The incidence, severity, and relationship to study treatment of adverse events will be assessed according to the Common Terminology Criteria for Adverse Events.	From the first dose through 30 days after the last dose, up to approximately 19 months
Quality of Life Score	Quality of life will be assessed using the EORTC QLQ-C30 questionnaire according to the study protocol.	Baseline to 24 months after randomization
Total Treatment Cost	Total treatment cost will be calculated from randomization to the final follow-up according to the study protocol.	From randomization to the end of follow-up, up to 60 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-Year Bladder-Intact Event-Free Survival Rate by Baseline HER2 IHC Category	Pretreatment tumor HER2 expression will be assessed by immunohistochemistry and categorized as IHC 2+ or IHC 3+. The percentage of participants meeting the 2-year bladder-intact event-free survival definition will be estimated separately for each HER2 IHC category. Bladder-intact event-free survival is defined as being alive with an intact bladder and without muscle-invasive bladder cancer recurrence, regional lymph node recurrence, distant metastasis, radical cystectomy, or bladder cancer-related death. The unit of measure is percentage of participants.	24 months after randomization

Collaborators and Investigators

• Sponsor: Tianjin Medical University Second Hospital
• Collaborators: The First Affiliated Hospital with Nanjing Medical University; Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): June 20, 2029
• Study Completion (Estimated): June 20, 2031

Study Registration Dates

• First Submitted: June 27, 2026
• First Submitted That Met QC Criteria: August 4, 2026
• First Posted (Actual): August 10, 2026

Study Record Updates

• Last Update Posted (Actual): August 10, 2026
• Last Update Submitted That Met QC Criteria: August 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Pelvic lymph node dissection; Toripalimab; Disitamab vedotin; Bladder-sparing therapy
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urologic Neoplasms; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Surgical Procedures, Operative; Urologic Surgical Procedures; Urogenital Surgical Procedures; disitamab vedotin; toripalimab; Transurethral Resection of Bladder; RC48 antibody
• Other Study ID Numbers: TMU2H-RC48-TORI-MIBC-2026-035

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The plan for sharing de-identified individual participant data has not been determined and will be decided after completion of the study, subject to approval by the sponsor, principal investigator, and ethics committee.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No