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

A Single-arm, Open Clinical Trial of Efficacy and Safety of Tislelizumab in Combination With Disitamab-vedotin as Neoadjuvant Therapy for HER2-positive High-risk Upper Tract Urothelial Carcinoma (UTUC)

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) .

Study Overview

• Status: Recruiting
• Conditions: Neoadjuvant Immunotherapy
• Intervention / Treatment: Drug: tislelizumab+disitamab-vedotin

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hailong Hu, MD,PhD; Phone Number: +86 13662096232; Email: hhllove2004@163.com

Study Locations

• China
  • Tianjin, China
    • Recruiting
    • The Second Hospital of Tianjin Medical University
    • Contact: Hailong Hu, MD,PhD; Phone Number: +86 13662096232; Email: hhllove2004@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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]).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tislelizumab+disitamab-vedotin	Drug: tislelizumab+disitamab-vedotin; Patients enrolled will receive 3 cycles of tislelizumab 200 mg in combination with disitamab-vedotin (RC48) 2.0mg/kg intravenously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pathological complete response (pCR)	no residual tumor was detected in the specimen from RNU/DU by pathological examination	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-related adverse events	Classified in accordance with CTCAE version 5.0	From treatment initiation to the end of treatment at 90 days.
overall survival	Defined as the time from treatment initiated to death from any cause	5 years since treatment initiation.
recurrence-free survival	defined as the time from treatment initiated to the first occurrence of tumor recurrence (including in the upper urinary tract, bladder or metastasis).	5 years since treatment initiation.
imaging complete response	no target lesions found in imaging examination	3 months.
imaging partial response	More than 30% decrease in sum of diameters of target lesion in imaging examination	3 months.
imaging progressive disease	More than 20% increase in sum of diameters or appearance of new lesions in imaging examination	3 months.
imaging stable disease		3 months.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
event-free kidney-sparing survival	Defined as the time from treatment initiation to the first occurrence of tumor recurrence that met the indications for RNU, metastatic disease or death from any cause	5 years since treatment initiation.

Collaborators and Investigators

• Sponsor: Tianjin Medical University Second Hospital
• Investigators: Principal Investigator: Hailong Hu, MD,PhD, Tianjin Medical University Second Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2022
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: April 14, 2023
• First Submitted That Met QC Criteria: April 20, 2023
• First Posted (Actual): May 1, 2023

Study Record Updates

• Last Update Posted (Actual): July 14, 2026
• Last Update Submitted That Met QC Criteria: July 12, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: immunotherapy; PD-1; neoadjuvant therapy; UTUC; ADC; upper tract urothelial carcinoma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Transitional Cell; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Immunoconjugates; Tislelizumab; Disitamab vedotin
• Other Study ID Numbers: TRUCE-UTUC01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No