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 a novel preoperative neoadjuvant immunotherapy for UTUC. To further observe the feasibility and safety of this regimen in the field of UTUC. In our study, patients enrolled will receive neoadjuvant tislelizumab in combination with disitamab-vedotin therapy followed by radical radical nephroureterectomy (RNU) or distal ureterectomy(DU).
• 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.