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

Phase 3Not Yet RecruitingNCT07756008

Tianjin Medical University Second Hospital114 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

114

Interventions

Disitamab Vedotin (RC48)DRUG

Disitamab vedotin will be administered in combination with toripalimab according to the study protocol.

ToripalimabDRUG

Toripalimab will be administered in combination with disitamab vedotin according to the study protocol.

Transurethral Resection of Bladder TumorPROCEDURE

Maximal transurethral resection of bladder tumor will be performed as part of the bladder-sparing treatment strategy.

Pelvic Lymph Node DissectionPROCEDURE

Standardized pelvic lymph node dissection will be performed in participants assigned to the PLND arm.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: 24 months after randomization

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: Up to 24 months after randomization

Overall Survival

Overall survival is defined as the time from randomization to death from any cause.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: From randomization to the end of follow-up, up to 60 months