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

Neoadjuvant Immunotherapy Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05837806
• Other study ID #: TRUCE-UTUC01
• Status: Recruiting
• Phase: Phase 2
• Start date: December 30, 2022
• Est. completion date: December 30, 2027

Study information

• Verified date: October 2023
• Source: Tianjin Medical University Second Hospital
• Contact: Hailong Hu, MD,PhD
• Phone: +86 13662096232
• Email: hhllove2004[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 a novel preoperative neoadjuvant immunotherapy for UTUC. To further observe the feasibility and safety of this regimen in the field of UTUC.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 27
• Est. completion date: December 30, 2027
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 1. diagnosed as high-risk upper uroepithelial carcinoma (according to CSCO2021 diagnostic criteria) by ureteroscopy or urinary exfoliation cytology, imaging (CT, MRI or PET-CT, etc.), clinical stage T1-T4N0-2M0; pathological tissue immunohistochemistry HER2 1~3+; 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 × 109/L, platelet count = 80 × 109/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 hypersensitivity to tirelizumab and vedicituzumab 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]).

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Neoadjuvant Immunotherapy

Intervention

Drug:
• tislelizumab+disitamab-vedotin
patients in group will receive 3 cycles of tislelizumab 200 mg in combination with disitamab-vedotin 120 mg intravenously.

Locations

Country	Name	City	State
China	The Second Hospital of Tianjin Medical University	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Tianjin Medical University Second Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	pCR	Defined as the percentage of patients with pT0N0 pathological findings after resection as a percentage of total patients	3 months