Efficacy and Safety of Tislelizumab in Combination With Disitamab-vedotin as Neoadjuvant Therapy for HER2-positive High-risk Upper Tract Urothelial Carcinoma (UTUC)

NCT ID: NCT05837806

Last Updated: 2025-12-31

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-30
• Study Completion Date: 2027-12-30

Brief Summary

Neoadjuvant chemotherapy treatment can be used for specific UTUC patients, especially for highly staged and/or grade tumors, such as kidneys with potentially decreased renal function after RNU. Neoadjuvant therapy is a series of treatments administered preoperatively for UTUC, mainly chemotherapy, and in recent years, novel therapies of immunotherapy have emerged. Since conventional cisplatin neoadjuvant regimens also require high preoperative renal function, neoadjuvant therapy regimens such as immunotherapy provide more effective and feasible treatments for patients who are intolerant to current cisplatin chemotherapy regimens. The aim of this study was to explore the efficacy and safety of the combination of disitamab vedotin, a human epidermal growth factor receptor-2 (HER-2) targeted ADC, and tislelizumab, a humanised PD-1 ICIs, as neoadjuvant treatment for non-metastatic, high-risk, HER-2 expressing UTUC. In our study, patients enrolled will receive neoadjuvant tislelizumab plus disitamab-vedotin therapy followed by radical nephroureterectomy (RNU), distal ureterectomy (DU) or ureteroscopic ablation (UA) .

Conditions

Neoadjuvant Immunotherapy

Keywords

neoadjuvant therapy; UTUC; immunotherapy; upper tract urothelial carcinoma; PD-1; ADC

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

tislelizumab+disitamab-vedotin

Group Type: EXPERIMENTAL

tislelizumab+disitamab-vedotin

Intervention Type: DRUG

Patients enrolled will receive 3 cycles of tislelizumab 200 mg in combination with disitamab-vedotin (RC48) 2.0mg/kg intravenously.

Interventions

tislelizumab+disitamab-vedotin

Patients enrolled will receive 3 cycles of tislelizumab 200 mg in combination with disitamab-vedotin (RC48) 2.0mg/kg intravenously.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Radiographically(CT, MRI or PET-CT, etc.) and histologically confirmed diagnosis of localized HER-2 expressing upper urothelial carcinoma( (cT1-4N0-2M0, HER-2 immunohistochemistry (IHC) ≥ 1+); high risk disease (according to EAU Guidelines for UTUC); planning to receive radical nephroureterectomy (RNU), distal ureterectomy (DU) or ureteroscopic ablation (UA).

2. Male or female aged 18 years and above;

3. Expected survival time greater than 12 weeks;

4. An ECOG status score of 0-2;

5. Agree to provide specimens of blood, urine, and tissue examination (for detection of MRD, PD-L1 expression, HER2 expression, tumor mutation load, immunohistochemistry, DNA and RNA detection, etc.);

6. The level of organ function must meet the following requirements:

• hematological indicators: absolute neutrophil count ≥ 1.5 × 10^9/L, platelet count ≥ 80 × 10^9/L, hemoglobin ≥ 6.0 g/dL (can be maintained by symptomatic treatment)
• hepatic function: total bilirubin ≤ 1.5 times the upper limit of normal, and glutathione and glutamic oxalacetic transaminase ≤ 2.5 times the upper limit of normal;
• renal function: GFR ≥ 15 ml/min;
• Subjects voluntarily joined the study, signed an informed consent form, were compliant, and cooperated with the follow-up.

Exclusion Criteria

1. Live attenuated vaccines, other than COVID-19 vaccine, received within 4 weeks prior to treatment or scheduled to be received during the study period

2. Active, known or suspected autoimmune disease;

3. Known history of primary immunodeficiency;

4. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation

5. Female patients who are pregnant or breastfeeding

6. Untreated acute or chronic active hepatitis B or C infection. Patients who are receiving antiviral therapy with monitoring of viral copy number and are eligible for enrollment as determined by the physician on an individual patient basis;

7. Previous use of immunosuppressive drugs, excluding nasal spray and inhaled corticosteroids or physiologic doses of systemic steroids (i.e., no more than 10 mg/day prednisolone or equivalent pharmacologic physiologic doses of other corticosteroids), within 4 weeks prior to initiation of therapy

8. Known or suspected allergy history to tislelizumab and disitamab vedotin.

9. With a clear history of active tuberculosis.

10. Prior PD-1/PD-L1/CTLA-4 antibody or other immunotherapy;

11. Those who are participating in other clinical studies

12. Men of reproductive potential or women with the potential to become pregnant who are not using reliable contraception

13. Uncontrolled co-morbidities, including but not limited to

• HIV-infected individuals (HIV-positive);
• Severe infections that are active or poorly controlled clinically (including patients in the period of neocoronavirus infection)
• Evidence of the presence of severe or uncontrolled systemic disease (e.g., severe psychiatric, neurological disease, epilepsy or dementia, unstable or uncompensated respiratory, cardiovascular, hepatic or renal disease, uncontrolled hypertension [i.e., defined as greater than or equal to CTCAE grade 2 hypertension despite medication]).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tianjin Medical University Second Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hailong Hu, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Tianjin Medical University Second Hospital

Locations

The Second Hospital of Tianjin Medical University

Tianjin, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Hailong Hu, MD,PhD

Role: CONTACT

Phone: +86 13662096232

Email: hhllove2004@163.com

Facility Contacts

Hailong Hu, MD,PhD

Role: primary

Other Identifiers

TRUCE-UTUC01

Identifier Type: -

Identifier Source: org_study_id