RC48 Combined With Tislelizumab: 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 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
85 Years
Healthy volunteers
No
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.
Primary outcome measure(s)
Kidney-Intact Event-Free Survival (KI-EFS) at 1 year — From enrollment to 12 months 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.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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