Upper Tract Urothelial CarcinomaPhase 2NCT07584733
Biomarker-Enriched Kidney-Preserving Strategy With Disitamab Vedotin Plus Tislelizumab in HER2-Positive High-Risk Upper Tract Urothelial Carcinoma
A Phase 2 study testing RC48 Combined With Tislelizumab in people with Upper Tract Urothelial Carcinoma, run by RenJi Hospital at 1 site in China.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Upper Tract Urothelial Carcinoma
- What is being tested?
- RC48 Combined With Tislelizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteChina
- Study dates
- 31 May 2026to 31 Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Ethics Committee of Shanghai Renji Hospital
Shanghai, Shanghai Municipality
Qi Lu, +86021-68383364, rjllb3364@163.com
About this study
Official title: 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)
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.
Read the detailed description
This is a prospective, multicentre, single-arm, phase II clinical trial designed to evaluate the efficacy and safety of a response-adapted kidney-preserving treatment strategy in patients with HER2-positive high-risk upper tract urothelial carcinoma (UTUC).
Eligible patients will receive neoadjuvant systemic therapy consisting of disitamab vedotin in combination with tislelizumab administered every 3 weeks for 2-4 cycles. Tumour response will be assessed after two cycles using radiographic evaluation and clinical assessment. Patients demonstrating clinical benefit will proceed to complete induction therapy, followed by comprehensive restaging including imaging, ureteroscopy with biopsy, and urine cytology.
Subsequent local treatment will be determined according to a predefined response-adapted algorithm. Patients meeting protocol-specified criteria will undergo kidney-sparing surgery (KSS), including segmental ureterectomy or endoscopic ablation depending on tumour location and anatomical feasibility. Patients not meeting criteria for KSS will undergo radical nephroureterectomy (RNU).
The primary objective of the study is to determine whether this multimodal strategy can achieve clinically meaningful oncologic control while preserving renal function in a biomarker-selected population.
In addition, longitudinal biospecimen collection will be conducted to evaluate the dynamics of urinary tumor DNA (utDNA) and circulating tumor DNA (ctDNA) as exploratory biomarkers of treatment response and minimal residual disease.
- Conditions
- Upper Tract Urothelial Carcinoma
- Being tested
- RC48 Combined With Tislelizumab
- Keywords
- upper tract urothelial carcinoma, Kidney-Preserving, Disitamab Vedotin, Tislelizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RC48 Combined With TislelizumabDrug
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 group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: RC48 Combined With Tislelizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From enrollment to 12 months
Secondary outcomes (6)
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.
Measured: Up to 24 months
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.
Measured: Up to 24 months
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
Measured: Immediately after Induction Therapy
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
Measured: 1 month after surgery
Renal Function Preservation
Change in estimated glomerular filtration rate (eGFR)
Measured: Up to 12 months
Safety and Tolerability
Incidence of treatment-related adverse events graded by CTCAE v5.0
Measured: Up to 90 days post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2026
- Study start31 May 2026 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Upper Tract Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by RenJi HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- RenJi Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- West China Hospital, Tianjin Medical University Second Hospital, Peking University First Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07584733
- Sponsor's protocol ID
- DISTINCT II
- Status last verified
- May 2026
- First submitted
- 4 May 2026
- Last updated
- 13 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT07584733
- Acronym / sponsor ID
- DISTINCT II
- Conditions
- Upper Tract Urothelial Carcinoma
- Keywords
- upper tract urothelial carcinoma, Kidney-Preserving, Disitamab Vedotin, Tislelizumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- RenJi HospitalUniversity, hospital or other
- Collaborators
- West China Hospital, Tianjin Medical University Second Hospital, Peking University First Hospital
- Study start
- 31 May 2026 (estimated)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 13 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a prospective, multicentre, single-arm, phase II clinical trial designed to evaluate the efficacy and safety of a response-adapted kidney-preserving treatment strategy in patients with HER2-positive high-risk upper tract urothelial carcinoma (UTUC).
Eligible patients will receive neoadjuvant systemic therapy consisting of disitamab vedotin in combination with tislelizumab administered every 3 weeks for 2-4 cycles. Tumour response will be assessed after two cycles using radiographic evaluation and clinical assessment. Patients demonstrating clinical benefit will proceed to complete induction therapy, followed by comprehensive restaging including imaging, ureteroscopy with biopsy, and urine cytology.
Subsequent local treatment will be determined according to a predefined response-adapted algorithm. Patients meeting protocol-specified criteria will undergo kidney-sparing surgery (KSS), including segmental ureterectomy or endoscopic ablation depending on tumour location and anatomical feasibility. Patients not meeting criteria for KSS will undergo radical nephroureterectomy (RNU).
The primary objective of the study is to determine whether this multimodal strategy can achieve clinically meaningful oncologic control while preserving renal function in a biomarker-selected population.
In addition, longitudinal biospecimen collection will be conducted to evaluate the dynamics of urinary tumor DNA (utDNA) and circulating tumor DNA (ctDNA) as exploratory biomarkers of treatment response and minimal residual disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant disitamab vedotin + tislelizumab followed by response-adapted surgery | Experimental | Drug: RC48 Combined With TislelizumabDrug: 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 |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RC48 Combined With TislelizumabIn 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. | Drug | Neoadjuvant disitamab vedotin + tislelizumab followed by response-adapted surgery |
Primary outcome
Kidney-Intact Event-Free Survival (KI-EFS) at 1 year
Time frame: 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.
6 secondary outcomes
Kidney-Intact Event-Free Survival at 2 years
Time frame: Up to 24 months
Disease-Free Survival (DFS) Renal Function Preservation
Time frame: Up to 24 months
Clinical Complete Response (cCR) Rate After Induction Therapy
Time frame: Immediately after Induction Therapy
Clinical Complete Response (cCR) Rate After Kidney-Sparing Surgery
Time frame: 1 month after surgery
Renal Function Preservation
Time frame: Up to 12 months
Safety and Tolerability
Time frame: Up to 90 days post-treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RC48 Combined With Tislelizumab in people with Upper Tract Urothelial Carcinoma, run by RenJi Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 13 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact jiwei huang (8613651682825, huangjiwei@renji.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Kidney-Intact Event-Free Survival (KI-EFS) at 1 year (time frame: From enrollment to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2026.