Urinary Tumor DNA-Guided Systemic Immunotherapy for Unresectable Very-High-Risk Non-Muscle-Invasive Bladder Cancer

NCT07475403 | Recruiting Phase 2 DMC

• 1 other identifier: Truce-LB03B
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 3

Brief Summary

This study evaluates whether urinary tumor DNA (utDNA) testing, together with clinical, pathologic, and radiographic assessment, can help guide treatment discontinuation and active surveillance in patients with unresectable very-high-risk non-muscle-invasive bladder cancer (VHR NMIBC) treated with bladder-sparing systemic immunotherapy. Participants receive systemic immune checkpoint inhibitor-based therapy every 3 weeks for an initial 3 cycles. Initial response assessment is performed using transurethral resection of bladder tumor (TURBT) and chest and abdominopelvic computed tomography (CT). Participants without progression to muscle-invasive, regional nodal, or distant metastatic disease then undergo post-TURBT urine cytology and urinary tumor DNA (utDNA) testing. Participants with both negative urine cytology and negative utDNA results receive an additional 3 cycles of systemic immunotherapy. After the additional treatment, participants undergo repeat evaluation using cystoscopy with biopsy, urine cytology, utDNA testing, and chest and abdominopelvic CT. Participants with negative findings on cystoscopic biopsy, urine cytology, and utDNA testing, and without radiographic evidence of nodal or distant metastatic disease, discontinue systemic immunotherapy and enter an active surveillance phase with regular follow-up monitoring. Participants who do not meet these criteria continue further clinical management and follow-up according to institutional practice. The study aims to determine whether a shortened duration of systemic immunotherapy guided by integrated molecular, clinical, pathologic, and radiographic response assessment can maintain favorable oncologic outcomes while reducing unnecessary treatment exposure in this high-risk population.

Conditions

Bladder Cancer; Liquid Biopsy; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Event-Free Survival

  Event-free survival is defined as the time from initiation of systemic immunotherapy to the first occurrence of any of the following events after entry into the active surveillance phase: histologically confirmed intravesical recurrence of urothelial carcinoma, progression to muscle-invasive bladder cancer (≥T2 disease), regional lymph node or distant metastasis identified on chest or abdominopelvic computed tomography (CT), radical cystectomy, or death from any cause.. Residual non-muscle-invasive bladder cancer identified during the initial TURBT-based response assessment is not considered an event. Isolated urinary tumor DNA (utDNA) positivity without pathologically confirmed disease recurrence or progression is not considered an event.

  Up to 2 years first administration of systemic immunotherapy

Secondary Outcomes (4)

• Duration of Complete Response

  Up to 2 years from first documented complete clinical response

• Radical Cystectomy-Free Survival

  Up to 2 years from first administration of systemic immunotherapy

• Overall Survival

  Up to 2 years from first administration of systemic immunotherapy

• Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  From first administration of systemic immunotherapy up to 30 days after last administration of study

Other Outcomes (3)

• EORTC QLQ-C30

  Up to 2 years from first administration of systemic immunotherapy

• EORTC QLQ-NMIBC24

  Up to 2 years from first administration of systemic immunotherapy

• EQ-5L

  Up to 2 vears from first administration of systemic immunotherapy

Study Arms (1)

Study group

EXPERIMENTAL

Drug: Systemic immunotherapy

Interventions

Systemic immunotherapy DRUG

Participants receive systemic immune checkpoint inhibitor-based therapy administered intravenously every 3 weeks for an initial 3 cycles. Treatment response is initially assessed using transurethral resection of bladder tumor (TURBT) to evaluate pathologic stage. Participants without progression to muscle-invasive or metastatic disease subsequently undergo post-TURBT urine cytology and urinary tumor DNA (utDNA) testing. Participants with both negative urine cytology and negative utDNA results receive an additional 3 cycles of systemic immunotherapy. Following the additional treatment, participants undergo repeat evaluation using cystoscopy with biopsy, urine cytology, and utDNA testing. Participants with negative findings on cystoscopic biopsy, urine cytology, and utDNA testing discontinue systemic immunotherapy and enter an active surveillance phase with regular follow-up monitoring. Participants who do not meet these criteria continue further clinical management and follow-up accord

Study group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years.
• Histologically confirmed non-muscle-invasive urothelial carcinoma of the bladder classified as very-high-risk (VHR) according to EAU 2025 guideline criteria.
• Disease considered unresectable by the investigator and multidisciplinary team, defined as complete tumor eradication by standard transurethral resection of bladder tumor (TURBT) being not feasible or unlikely to achieve adequate local control.
• Patients who are ineligible or refuse for radical cystectomy, after discussion with the treating team.
• At least one measurable or evaluable bladder lesion/documented residual disease suitable for response assessment by cystoscopy, TURBT/biopsy, pathology, urine cytology, and urinary tumor DNA (utDNA) testing.
• ECOG performance status 0-2.
• Adequate organ function, including:
• Hematologic function: Absolute neutrophil count ≥1.5 × 10⁹/L, Platelet count ≥100 × 10⁹/L, Hemoglobin ≥9 g/dL Hepatic function: Total bilirubin ≤1.5 × ULN, AST ≤2.5 × ULN, ALT ≤2.5 × ULN Renal function: Serum creatinine ≤1.5 × ULN or Creatinine clearance ≥60 mL/min.
• Ability to provide urine samples for utDNA testing and urine cytology during treatment and follow-up.

You may not qualify if:

• Muscle-invasive bladder cancer (≥T2), locally advanced unresectable invasive disease beyond NMIBC, or metastatic urothelial carcinoma at baseline.
• Histology showing predominant or pure non-urothelial carcinoma of the bladder that, in the investigator's judgment, would make the patient unsuitable for this protocol.
• Prior treatment with immune.
• Active autoimmune disease or history of autoimmune disease requiring systemic immunosuppressive treatment and considered incompatible with immune checkpoint inhibitor therapy.
• Ongoing systemic immunosuppressive therapy exceeding protocol-allowed doses.
• \. Active uncontrolled infection, including uncontrolled urinary tract infection, that would interfere with study treatment or response assessment.
• \. Any medical condition that would preclude safe administration of systemic immunotherapy or protocol-required cystoscopy/TURBT/biopsy, in the investigator's judgment.
• \. Concurrent other malignancy. 10. Pregnant or breastfeeding women. 11. Inability to comply with protocol procedures or follow-up.

Sponsors & Collaborators

• Tianjin Medical University Second Hospital: lead

Study Sites (3)

The Second Hospital of Tianjin Medical University

Tianjin, 300000, China

RECRUITING

Tianjin Hospital

Tianjin, China

RECRUITING

Xingtai People's Hospital

Xingtai, China

RECRUITING

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Central Study Contacts

Hailong Hu

CONTACT

+8619801518556; huhailong@tmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2026
• First Posted: March 16, 2026
• Study Start: March 16, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2029
• Last Updated: May 26, 2026

Record last verified: 2026-05

Locations

CN (3)