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) .
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;
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
Single group
tislelizumab+disitamab-vedotin
DrugPatients enrolled will receive 3 cycles of tislelizumab 200 mg in combination with disitamab-vedotin (RC48) 2.0mg/kg intravenously.
pathological complete response (pCR)
no residual tumor was detected in the specimen from RNU/DU by pathological examination
Treatment-related adverse events
Classified in accordance with CTCAE version 5.0
overall survival
Defined as the time from treatment initiated to death from any cause
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).
imaging complete response
no target lesions found in imaging examination
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
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