Clinical trial · Interventional
Biomarker-Enriched Kidney-Preserving Strategy With Disitamab Vedotin Plus Tislelizumab in HER2-Positive High-Risk Upper Tract Urothelial Carcinoma
A Prospective, Multicentre, Single-Arm Phase II Study Evaluating a Response-Adapted Kidney-Preserving Strategy Using Neoadjuvant Disitamab Vedotin Plus Tislelizumab in Patients With HER2-Positive High-Risk Upper Tract Urothelial Carcinoma (DISTINCT-II)
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This is a prospective, multicentre, single-arm phase II study evaluating a response-adapted kidney-preserving strategy in patients with HER2-positive high-risk upper tract urothelial carcinoma (UTUC). Patients will receive neoadjuvant disitamab vedotin plus tislelizumab, followed by response-adapted local treatment, including kidney-sparing surgery or radical nephroureterectomy based on predefined criteria. The primary objective is to assess whether this multimodal strategy can achieve clinically meaningful oncologic control while preserving renal function, as measured by 1-year kidney-intact event-free survival (KI-EFS). Secondary and exploratory objectives include evaluation of clinical response, survival outcomes, safety, renal function preservation, and longitudinal dynamics of circulating and urinary tumor DNA.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Upper Tract Urothelial Carcinoma | Renal Pelvis and Ureter Carcinoma | CURATED_BROADER | 0.80 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| RC48 Combined With Tislelizumab | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Neoadjuvant disitamab vedotin + tislelizumab followed by response-adapted surgery
- description
- Drug: Disitamab Vedotin Administered intravenously at 2.0 mg/kg every 3 weeks Drug: Tislelizumab Administered intravenously at 200 mg every 3 weeks Procedure: Surgery Kidney-sparing surgery (segmental ureterectomy or endoscopic ablation) or radical nephroureterectomy based on predefined criteria
- interventionNames
- Drug: RC48 Combined With Tislelizumab
Primary outcomes (1)
- measure
- Kidney-Intact Event-Free Survival (KI-EFS) at 1 year
- timeFrame
- From enrollment to 12 months
- description
- KI-EFS is defined as the time from study enrollment to the first occurrence of any of the following events: High-risk recurrence of upper tract urothelial carcinoma (local, regional, or distant), defined according to prespecified clinical or radiographic criteria Death from any cause Conversion to radical nephroureterectomy (RNU) for any reason Patients without an event will be censored at the date of last disease assessment.
Secondary outcomes (6)
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 85 Years
Show eligibility criteria text
Inclusion Criteria: * Age ≥18 years at the time of informed consent. * Histologically confirmed upper tract urothelial carcinoma (UTUC) arising from the renal pelvis or ureter, based on ureteroscopic biopsy. * High-risk UTUC, defined by at least one of the following features: Tumour size ≥2 cm; High-grade cytology or biopsy; Radiographic evidence of local invasion (≥cT2); Hydronephrosis; Multifocal disease * Clinical stage cT1-T3, N0-N1, M0, based on radiographic assessment. * N1 disease is permitted only if lymph nodes are considered resectable. * HER2-positive disease, defined as immunohistochemistry (IHC) score of 1+，2+ or 3+ on tumour tissue, assessed according to predefined criteria. * At least one measurable lesion according to RECIST version 1.1. * ECOG performance status of 0-1 * Adequate organ function, including: Hematologic function; Hepatic function; Renal function (no strict upper/lower limit required); * Patients must be considered potential candidates for a kidney-preserving treatment strategy, including: Absolute or relative indication for renal preservation (e.g., solitary kidney, baseline renal insufficiency), or Strong preference for kidney preservation after multidisciplinary discussion * Ability to understand and willingness to sign written informed consent. Exclusion Criteria: * Evidence of distant metastatic disease (M1). * Unresectable or bulky nodal disease (≥N2) not amenable to curative-intent surgery. * Prior systemic therapy for urothelial carcinoma, including:Chemotherapy; Immunotherapy; HER2-targeted therapy. * Prior radical nephroureterectomy for current disease. * Active autoimmune disease requiring systemic treatment within the past 2 years. * Current use of immunosuppressive medication, excluding physiologic doses of corticosteroids. * Uncontrolled intercurrent illness, including but not limited to: Active infection requiring systemic therapy; Uncontrolled cardiovascular disease; Significant pulmonary disease * Known active hepatitis B, hepatitis C, or HIV infection with uncontrolled viral replication. * History of another malignancy within the past 5 years, except: Adequately treated basal cell carcinoma; Squamous cell skin cancer; In situ carcinoma. * Pregnant or breastfeeding women. * Any condition that, in the opinion of the investigator, would interfere with study participation or interpretation of results.
References
Publications (0)
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