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

Tianjin Medical University Second Hospital

Status and phase: Enrolling; Phase 2

Conditions: Bladder Cancer; Immunotherapy; Liquid Biopsy

Treatments: Drug: Systemic immunotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT07475403

Truce-LB03

Details and patient eligibility

About

This study aims to evaluate whether urinary tumor DNA (utDNA) can guide treatment duration in patients with unresectable very-high-risk non-muscle-invasive bladder cancer (VHR NMIBC) who achieve complete clinical response after systemic immunotherapy.

Participants will receive systemic immunotherapy followed by response assessment using pathology, cystoscopy, urine cytology, and utDNA testing. Patients who achieve complete clinical response will receive a short additional course of immunotherapy before stopping treatment according to the study protocol.

The study hypothesizes that a shortened duration of systemic immunotherapy guided by utDNA monitoring may maintain favorable oncologic outcomes in this population.

Enrollment: 53 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥18 years.

2. Histologically confirmed non-muscle-invasive urothelial carcinoma of the bladder classified as very-high-risk (VHR) according to EAU 2025 guideline criteria.

3. 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.

4. Patients who are ineligible or refuse for radical cystectomy, after discussion with the treating team.

5. 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.

6. ECOG performance status 0-2.

7. 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.

8. Ability to provide urine samples for utDNA testing and urine cytology during treatment and follow-up.

Exclusion criteria

1. Muscle-invasive bladder cancer (≥T2), locally advanced unresectable invasive disease beyond NMIBC, or metastatic urothelial carcinoma at baseline.
2. 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.
3. Prior treatment with immune.
4. Active autoimmune disease or history of autoimmune disease requiring systemic immunosuppressive treatment and considered incompatible with immune checkpoint inhibitor therapy.
5. Ongoing systemic immunosuppressive therapy exceeding protocol-allowed doses.

7. Active uncontrolled infection, including uncontrolled urinary tract infection, that would interfere with study treatment or response assessment.

8. Any medical condition that would preclude safe administration of systemic immunotherapy or protocol-required cystoscopy/TURBT/biopsy, in the investigator's judgment.

9. Concurrent other malignancy. 10. Pregnant or breastfeeding women. 11. Inability to comply with protocol procedures or follow-up.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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53 participants in 1 patient group

Study group

Experimental group

Treatment:

Drug: Systemic immunotherapy