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

NCT05837806 | Recruiting Phase 2

• 1 other identifier: TRUCE-UTUC01
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• pathological complete response (pCR)

  no residual lesions were found in the imaging examination, negative urine cytology and pathological examination showed no tumor was detected in the specimen from radical nephroureterectomy (RNU), distal ureterectomy (DU) or ureteroscopic ablation (UA).

  3 months

Study Arms (1)

tislelizumab+disitamab-vedotin

EXPERIMENTAL

Drug: tislelizumab+disitamab-vedotin

Interventions

tislelizumab+disitamab-vedotin DRUG

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

tislelizumab+disitamab-vedotin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Male or female aged 18 years and above;
• Expected survival time greater than 12 weeks;
• An ECOG status score of 0-2;
• 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.);
• 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.

You may not qualify if:

• Live attenuated vaccines, other than COVID-19 vaccine, received within 4 weeks prior to treatment or scheduled to be received during the study period
• Active, known or suspected autoimmune disease;
• Known history of primary immunodeficiency;
• Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation
• Female patients who are pregnant or breastfeeding
• 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;
• 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
• Known or suspected allergy history to tislelizumab and disitamab vedotin.
• With a clear history of active tuberculosis.
• Prior PD-1/PD-L1/CTLA-4 antibody or other immunotherapy;
• Those who are participating in other clinical studies
• Men of reproductive potential or women with the potential to become pregnant who are not using reliable contraception
• 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)

Sponsors & Collaborators

• Tianjin Medical University Second Hospital: lead

Study Sites (1)

The Second Hospital of Tianjin Medical University

Tianjin, China

RECRUITING

Study Officials

• Hailong Hu, MD,PhD

  Tianjin Medical University Second Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hailong Hu, MD,PhD

CONTACT

+86 13662096232; hhllove2004@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2023
• First Posted: May 1, 2023
• Study Start: December 30, 2022
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2027
• Last Updated: December 31, 2025

Record last verified: 2025-06

Locations

CN (1)