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.
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.
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.
Single group
RC48 Combined With Tislelizumab
DrugIn 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.
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.
Kidney-Intact Event-Free Survival at 2 years
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.
Disease-Free Survival (DFS) Renal Function Preservation
Time from definitive local treatment (KSS or RNU) to upper tract recurrence or death from any cause. Isolated bladder recurrence will not be counted as an event.
Clinical Complete Response (cCR) Rate After Induction Therapy
Clinical complete response (cCR) was defined as concordant negative findings on cross-sectional imaging, ureteroscopy, urine cytology, and targeted biopsy according to predefined criteria
Clinical Complete Response (cCR) Rate After Kidney-Sparing Surgery
Clinical complete response (cCR) was defined as concordant negative findings on cross-sectional imaging, ureteroscopy, urine cytology, and targeted biopsy according to predefined criteria
ctDNA/utDNA Dynamics
Detection tumor DNA (ctDNA/utDNA) using a fixed deep-sequencing panel.
HER2 expression level Exploratory Molecular Analyses
HER2 expression level pre-Induction Therapy
Click on the lead sponsor to view all of their trials.
RenJi Hospital
Lead sponsor
West China Hospital
Collaborator
Tianjin Medical University Second Hospital
Collaborator
Peking University First Hospital
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
