Biomarker-Enriched Kidney-Preserving Strategy With Disitamab Vedotin Plus Tislelizumab in HER2-Positive High-Risk Upper Tract Urothelial Carcinoma

NCT07584733 | Not Yet Recruiting Phase 2

• 1 other identifier: DISTINCT II
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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

Upper Tract Urothelial Carcinoma

Keywords

upper tract urothelial carcinoma; Kidney-Preserving; Disitamab Vedotin; Tislelizumab

Outcome Measures

Primary Outcomes (1)

• Kidney-Intact Event-Free Survival (KI-EFS) at 1 year

  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.

  From enrollment to 12 months

Secondary Outcomes (6)

• Kidney-Intact Event-Free Survival at 2 years

  Up to 24 months

• Disease-Free Survival (DFS) Renal Function Preservation

  Up to 24 months

• Clinical Complete Response (cCR) Rate After Induction Therapy

  Immediately after Induction Therapy

• Clinical Complete Response (cCR) Rate After Kidney-Sparing Surgery

  1 month after surgery

• Renal Function Preservation

  Up to 12 months

Other Outcomes (2)

• ctDNA/utDNA Dynamics

  Up to 12 months

• HER2 expression level Exploratory Molecular Analyses

  baseline, pre-Induction Therapy

Study Arms (1)

Neoadjuvant disitamab vedotin + tislelizumab followed by response-adapted surgery

EXPERIMENTAL

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

Drug: RC48 Combined With Tislelizumab

Interventions

RC48 Combined With Tislelizumab DRUG

In this trial, RC48 was scheduled to be administered at a dose of 2.0 mg/kg every 3 weeks, with the first dose on day 1 of the first cycle. Tislelizumab was administered at a dose of 200 mg every 3 weeks, with the first dose on day 1 of the first 21-day cycle. The drug is diluted with normal saline and administered by intravenous drip for one hour.

Neoadjuvant disitamab vedotin + tislelizumab followed by response-adapted surgery

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• RenJi Hospital: lead
• West China Hospital: collaborator
• Tianjin Medical University Second Hospital: collaborator
• Peking University First Hospital: collaborator

Study Sites (1)

Ethics Committee of Shanghai Renji Hospital

Shanghai, Shanghai Municipality, China

Location

MeSH Terms

Interventions

tislelizumab

Central Study Contacts

jiwei huang

CONTACT

8613651682825; huangjiwei@renji.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: This is a prospective, open, multiple-center clinical study of renal preservation therapy in high-risk upper urinary tract urothelial carcinoma patients . The study was conducted in accordance with the Good Practice for Quality Control of Clinical Trials for Pharmaceutical Products (GCP). Approximately 20 subjects will be enrolled to evaluate the efficacy and safety of RC48 (2.0 mg/kg intravenously every 3 weeks) combined with Tislelizumab (200mg intravenously every 3 weeks).
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: In this trial, RC48 was scheduled to be administered at a dose of 2.0 mg/kg every 3 weeks, with the first dose on day 1 of the first cycle. Tislelizumab was administered at a dose of 200 mg every 3 weeks, with the first dose on day 1 of the first 21-day cycle. The drug is diluted with normal saline and administered by intravenous drip for one hour.

Study Record Dates

• First Submitted: May 4, 2026
• First Posted: May 13, 2026
• Study Start (Estimated): May 31, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: May 13, 2026

Record last verified: 2026-05

Locations

CN (1)