UTUCPhase 2NCT07741448
Neoadjuvant Gemcitabine Plus Trastuzumab Rezetecan in HER2-positive UTUC
A Phase 2 study testing Trastuzumab Rezetecan, Gemcitabine and Radical nephroureterectomy in people with UTUC, run by Zhiquan Hu at 10 sites in China.
Trial summary
Upper tract urothelial carcinoma (UTUC) carries a poor prognosis, with conventional GC (gemcitabine plus cisplatin) regimens achieving only a 19% pathological complete response (pCR) rate in the neoadjuvant setting. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- UTUC
- What is being tested?
- Trastuzumab Rezetecan, Gemcitabine and Radical nephroureterectomy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 10 sitesChina
- Study dates
- 15 Aug 2026to 15 Aug 2029
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The subject voluntarily participates in the study, provides written informed consent, and is able to comply with study procedures and follow-up visits.
- Aged between 18 and 75 years.
- Patients diagnosed with upper tract urothelial carcinoma (UTUC) who are candidates for radical nephroureterectomy with bladder cuff excision.
- Clinical stage T1N0M0 - T2-T4aN1M0 (evaluated by CT/MRI/PET-CT).
- Histopathology confirms urothelial carcinoma as the predominant component; IHC testing shows HER2 expression of 2+ to 3+.
- ECOG performance status ≤ 2.
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- Laboratory parameters meet all of the following criteria:
- Absolute neutrophil count ≥ 1.5 × 10⁹/L
- Platelets ≥ 100 × 10⁹/L; hemoglobin ≥ 90 g/L
- Total bilirubin ≤ 1.5 × ULN
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) ≤ 2.5 × ULN; serum creatinine ≤ 3 × ULN
- Cardiac function: New York Heart Association (NYHA) classification < Grade III.
Who cannot join
- Received live attenuated vaccines within 4 weeks prior to enrollment or plan to receive such vaccines during the study.
- Received systemic chemotherapy, anti-PD-1/PD-L1 agents, or HER2-targeted therapy within the previous 6 months.
- Known hypersensitivity to gemcitabine, Trastuzumab Rezetecan, or any of their excipients.
- Active, known or suspected autoimmune disease.
- Known history of primary immunodeficiency.
- Known history of solid organ allotransplantation or allogeneic hematopoietic stem cell transplantation.
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- Female patients who are pregnant or breastfeeding.
- Untreated acute or chronically active hepatitis B or hepatitis C infection. Patients receiving antiviral therapy may be considered eligible at the investigator's discretion with ongoing viral load monitoring.
- Uncontrolled concurrent illnesses, including but not limited to:
- HIV infection (positive HIV antibody).
- Severe active infection with inadequate clinical control.
- Evidence of severe or uncontrolled systemic disease (e.g., severe psychiatric or neurological disorders, epilepsy or dementia; unstable or decompensated respiratory, cardiovascular, hepatic or renal disease; uncontrolled hypertension defined as CTCAE Grade ≥2 hypertension despite medical treatment).
- Active bleeding, newly diagnosed thromboembolic disease requiring therapeutic anticoagulation, or bleeding diathesis.
- Diagnosis of another malignant tumor within the past 5 years.
- Active tuberculosis
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
10 sites in 1 country
China10 sites, 10 recruiting
- Recruiting
Huanggang Central Hospital
Huanggang, Hubei, 438000
Jiayi Tao, M.D., 86+13409868766, 35149051@qq.com
Jiayi Tao, M.D.
- Recruiting
Jingzhou Central Hospital
Jingzhou, Hubei, 434020
Yixiang Liao, M.D., 86+18107167675, 25261193@qq.com
Yixiang Liao
- Recruiting
Taihe Hospital
Shiyan, Hubei, 442000
Congbo Chen, M.D., 86+13907204825
Congbo Chen, M.D.
- Recruiting
The Central Hospital of Wuhan
Wuhan, Hubei, 430014
Yonglian Guo, M.D., 86+15972152299, 15972152299@139.com
Yonglian Guo, M.D.
- Recruiting
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technolog
Wuhan, Hubei, 430030
Zhiquan Hu, M.D., 86+13971656164, huzhiquan2000@163.com
Chunguang Yang, M.D.
- Recruiting
Renmin Hospital of Wuhan University
Wuhan, Hubei, 430060
Zhiyuan Chen, M.D., 86+13886000807, chenzhiyuan163@163.com
Zhiquan Chen, M.D.
- Recruiting
Zhongnan Hospital of Wuhan University
Wuhan, Hubei, 430071
Xingyuan Xiao, M.D., 86+18672923313, xiaoxingyuan@whu.edu.cn
Xingyuan Xiao, M.D.
- Recruiting
Hubei Cancer Hospital
Wuhan, Hubei, 430079
Youyuan Li, M.D., 86+18871188109
Youyuan Li, M.D.
- Recruiting
Xiangyang Central Hospital
Xiangyang, Hubei, 441021
Bin chen, M.D., 86+19908671399, 625848080@qq.com
Bin Chen, M.D.
- Recruiting
Yichang Central People's Hospital
Yichang, Hubei, 443003
Xiaobo Chen, M.D., 86+13972587419, 272899447@qq.com
Xiaobo Chen, M.D.
About this study
Official title: An Open-label, Single-arm, Multicenter Phase II Clinical Study to Evaluate Neoadjuvant Gemcitabine Combined With Trastuzumab Rezetecan in HER2-positive Upper Tract Urothelial Carcinoma
Upper tract urothelial carcinoma (UTUC) carries a poor prognosis, with conventional GC (gemcitabine plus cisplatin) regimens achieving only a 19% pathological complete response (pCR) rate in the neoadjuvant setting. Antibody-drug conjugates (ADCs) have shown promising results in advanced urothelial carcinoma, Meanwhile the clinical application of traditional cisplatin-based chemotherapy is associated with significant limitations. Therefore, exploring the efficacy and safety of Trastuzumab Rezetecan (an anti-HER2 ADC) combined with gemcitabine in UTUC is of considerable importance.
This trial will enroll patients with HER2 2-3+ UTUC. After pathological diagnosis, patients will receive intravenous infusions of gemcitabine and Trastuzumab Rezetecan. The treatment regimen consists of a 21-day cycle: 4 cycles of neoadjuvant therapy, followed by 2 cycles of adjuvant therapy for patients who do not achieve pCR (total of 6 cycles). For patients with suboptimal pathological downstaging after surgery (≥ypT3 or ypN+), combination with immune checkpoint inhibitors (ICIs) is recommended.
Read more
During the neoadjuvant period, adverse events will be closely monitored. Regular imaging and follow-up assessments will be performed, and events such as disease recurrence, progression, and their corresponding time points will be documented.
The primary endpoint is pCR rate. Secondary endpoints include adverse events during the neoadjuvant period, event-free survival (EFS), overall survival (OS).
- Conditions
- UTUC
- Being tested
- Trastuzumab Rezetecan, Gemcitabine, Radical nephroureterectomy
- Keywords
- Trastuzumab Rezetecan, Gemcitabine, UTUC, neoadjuvant therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trastuzumab RezetecanDrug
Gemcitabine 1000 mg/m² is given via intravenous infusion, followed by intravenous administration of trastuzumab rezetecan 4.8 mg/kg 3 hours thereafter. The treatment consists of 4 cycles in total with a 21-day cycle interval. Patients without pathological complete response (pCR) will receive 2 cycles of adjuvant therapy
GemcitabineDrug
Gemcitabine 1000 mg/m² is given via intravenous infusion, followed by intravenous administration of trastuzumab rezetecan 4.8 mg/kg 3 hours thereafter. The treatment consists of 4 cycles in total with a 21-day cycle interval. Patients without pathological complete response will receive 2 cycles of adjuvant therapy
Radical nephroureterectomyProcedure or surgery
After completing four cycles of neoadjuvant therapy, patients undergo radical nephroureterectomy (RNU). The surgical resection typically includes:
- The affected kidney (including the perirenal fat capsule); 2) The entire ureter from the renal pelvis to the intramural segment; 3) A bladder cuff around the ureteral orifice; 4) In addition, ipsilateral regional lymph node dissection (e.g., hilar, para-aortic, and paracaval nodes) may be performed depending on tumor stage and clinical indication.
| Study group | Role | What they receive |
|---|---|---|
| Trastuzumab Rezetecan plus Gemcitabine Group | Experimental | Not described Receives: Drug: Trastuzumab Rezetecan; Drug: Gemcitabine; Procedure: Radical nephroureterectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological Complete Response (pCR)
Defined as the absence of residual viable tumor cells (ypT0N0) in RNU specimens. Assessed post surgery. Method: A central pathology review committee performs review of slides from all eligible patients. Two senior uropathologists (associate professor level or above) read independently; consensus is final, otherwise a third senior pathologist adjudicates blindly. ypT and ypN are recorded.
Measured: Within 1 week after completion of radical nephroureterectomy
Secondary outcomes (1)
Treatment Related Adverse Events During Neoadjuvant Therapy
The patients will be evaluated according to CTCAE 5.0 during neoadjuvant therapy. Assessed from the first cycle to 4 weeks after the last cycle, with comprehensive tests each cycle, a scheduled visit 1 week after the last dose of each cycle, and immediate evaluation upon any alert or complaint. Method: Uniform site training, structured eCRF recording of AE terms, dates, grades, relatedness, actions, outcomes. An independent Clinical Endpoint Committee conducts centralized review of all Grade ≥3 events for final adjudication.
Measured: The period starting from the first administration of neoadjuvant therapy and extending through 4 weeks following the last dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2026
- Study start15 Aug 2026 (estimated)
- Primary completion15 Aug 2028 (estimated)
- Study completion15 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for UTUCStudies of the same condition, open and under way.
- 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
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhiquan Hu
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Zhiquan Hu, Tongji Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07741448
- Sponsor's protocol ID
- [226] LSZ (S023) No
- Status last verified
- Jul 2026
- First submitted
- 29 Jul 2026
- Last updated
- 3 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Single-arm, Multicenter Phase II Clinical Study to Evaluate Neoadjuvant Gemcitabine Combined With Trastuzumab Rezetecan in HER2-positive Upper Tract Urothelial Carcinoma
- ClinicalTrials.gov ID
- NCT07741448
- Acronym / sponsor ID
- [226] LSZ (S023) No
- Conditions
- UTUC
- Keywords
- Trastuzumab Rezetecan, Gemcitabine, UTUC, neoadjuvant therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Zhiquan HuUniversity, hospital or other
- Study start
- 15 Aug 2026 (estimated)
- Primary completion
- 15 Aug 2028 (estimated)
- Study completion
- 15 Aug 2029 (estimated)
- First posted
- 3 Aug 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.
Upper tract urothelial carcinoma (UTUC) carries a poor prognosis, with conventional GC (gemcitabine plus cisplatin) regimens achieving only a 19% pathological complete response (pCR) rate in the neoadjuvant setting. Antibody-drug conjugates (ADCs) have shown promising results in advanced urothelial carcinoma, Meanwhile the clinical application of traditional cisplatin-based chemotherapy is associated with significant limitations. Therefore, exploring the efficacy and safety of Trastuzumab Rezetecan (an anti-HER2 ADC) combined with gemcitabine in UTUC is of considerable importance.
This trial will enroll patients with HER2 2-3+ UTUC. After pathological diagnosis, patients will receive intravenous infusions of gemcitabine and Trastuzumab Rezetecan. The treatment regimen consists of a 21-day cycle: 4 cycles of neoadjuvant therapy, followed by 2 cycles of adjuvant therapy for patients who do not achieve pCR (total of 6 cycles). For patients with suboptimal pathological downstaging after surgery (≥ypT3 or ypN+), combination with immune checkpoint inhibitors (ICIs) is recommended.
During the neoadjuvant period, adverse events will be closely monitored. Regular imaging and follow-up assessments will be performed, and events such as disease recurrence, progression, and their corresponding time points will be documented.
The primary endpoint is pCR rate. Secondary endpoints include adverse events during the neoadjuvant period, event-free survival (EFS), overall survival (OS).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Trastuzumab Rezetecan plus Gemcitabine Group | Experimental | Drug: Trastuzumab Rezetecan, Drug: Gemcitabine, Procedure: Radical nephroureterectomy |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- The subject voluntarily participates in the study, provides written informed consent, and is able to comply with study procedures and follow-up visits.
- Aged between 18 and 75 years.
- Patients diagnosed with upper tract urothelial carcinoma (UTUC) who are candidates for radical nephroureterectomy with bladder cuff excision.
- Clinical stage T1N0M0 - T2-T4aN1M0 (evaluated by CT/MRI/PET-CT).
- Histopathology confirms urothelial carcinoma as the predominant component; IHC testing shows HER2 expression of 2+ to 3+.
Key exclusion criteria (15 listed)
- Received live attenuated vaccines within 4 weeks prior to enrollment or plan to receive such vaccines during the study.
- Received systemic chemotherapy, anti-PD-1/PD-L1 agents, or HER2-targeted therapy within the previous 6 months.
- Known hypersensitivity to gemcitabine, Trastuzumab Rezetecan, or any of their excipients.
- Active, known or suspected autoimmune disease.
- Known history of primary immunodeficiency.
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 |
|---|---|---|
| Trastuzumab RezetecanGemcitabine 1000 mg/m² is given via intravenous infusion, followed by intravenous administration of trastuzumab rezetecan 4.8 mg/kg 3 hours thereafter. The treatment consists of 4 cycles in total with a 21-day cycle interval. Patients without pathological complete response (pCR) will receive 2 cycles of adjuvant therapy | Drug | Trastuzumab Rezetecan plus Gemcitabine Group |
| GemcitabineGemcitabine 1000 mg/m² is given via intravenous infusion, followed by intravenous administration of trastuzumab rezetecan 4.8 mg/kg 3 hours thereafter. The treatment consists of 4 cycles in total with a 21-day cycle interval. Patients without pathological complete response will receive 2 cycles of adjuvant therapy | Drug | Trastuzumab Rezetecan plus Gemcitabine Group |
| Radical nephroureterectomyAfter completing four cycles of neoadjuvant therapy, patients undergo radical nephroureterectomy (RNU). The surgical resection typically includes: 1) The affected kidney (including the perirenal fat capsule); 2) The entire ureter from the renal pelvis to the intramural segment; 3) A bladder cuff around the ureteral orifice; 4) In addition, ipsilateral regional lymph node dissection (e.g., hilar, para-aortic, and paracaval nodes) may be performed depending on tumor stage and clinical indication. | Procedure or surgery | Trastuzumab Rezetecan plus Gemcitabine Group |
Primary outcome
Pathological Complete Response (pCR)
Time frame: Within 1 week after completion of radical nephroureterectomy
Defined as the absence of residual viable tumor cells (ypT0N0) in RNU specimens. Assessed post surgery. Method: A central pathology review committee performs review of slides from all eligible patients. Two senior uropathologists (associate professor level or above) read independently; consensus is final, otherwise a third senior pathologist adjudicates blindly. ypT and ypN are recorded.
1 secondary outcome
Treatment Related Adverse Events During Neoadjuvant Therapy
Time frame: The period starting from the first administration of neoadjuvant therapy and extending through 4 weeks following the last dose.
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 3 Aug 2026.
- Individual participant dataSharing planned: Undecided
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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.
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Trastuzumab Rezetecan, Gemcitabine and Radical nephroureterectomy in people with UTUC, run by Zhiquan Hu at 10 sites 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 12 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 3 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites 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 Zhiquan Hu, M.D. (86+13971656164, huzhiquan2000@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathological Complete Response (pCR) (time frame: Within 1 week after completion of radical nephroureterectomy). 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 3 Aug 2026.