Clinical trial NCT05837806: Efficacy and Safety of Tislelizumab in Combination With Disitamab-vedotin as Neoadjuvant Therapy for HER2-positive High-risk Upper Tract Urothelial Carcinoma (UTUC)
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Neoadjuvant Immunotherapy
Keywords: neoadjuvant therapy
UTUC
immunotherapy
upper tract urothelial carcinoma
PD-1
ADC
Lead sponsor: Tianjin Medical University Second Hospital
Sponsor class: OTHER
First posted: 2023-05-01
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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 \[i.e., defined as greater than or equal to CTCAE grade 2 hypertension despite medication\]).

Primary outcomes:
measure: pCR
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: Tianjin
country: China
facility: The Second Hospital of Tianjin Medical University
Study officials:
affiliation: Tianjin Medical University Second Hospital
name: Hailong Hu, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: