253TiP - WUTSUP-02-II-Neo-Dis-Tis: Investigating the efficacy and safety of neoadjuvant tislelizumab plus disitamab vedotin with adjuvant tislelizumab in upper urinary tract carcinoma: A phase II multi-center study

Background

Upper tract urothelial carcinoma (UTUC) and urothelial bladder cancer (UBC) exhibit varying biological behaviors, prognostic outcomes, and responses to treatment. Despite the superior outcomes of neoadjuvant treatment over adjuvant treatment in UBC trials, the currently available evidence for neoadjuvant therapy of UTUC remains limited. Additionally, the limited number of neoadjuvant trials for UTUC primarily utilize chemotherapy-based regimens, with little investigation into combination therapies. Of note, UTUC patients frequently have impaired renal functions, making a chemotherapy-independent approach a desirable alternative. Tislelizumab has demonstrated efficacy in patients with advanced or metastatic urothelial carcinoma. Disitamab Vedotin, a HER2-targeting antibody-drug conjugate (ADC),has demonstrated robust clinical efficacy in metastatic urothelial carcinoma patients with HER2 2+ or 3+ expression. Disitamab Vedotin in combination with PD-1 immunotherapy has shown remarkable results in locally advanced or metastatic urothelial carcinoma, regardless of HER2 expression, indicative of a synergistic effect between ADC and PD-1 immunotherapy. In this study, we aim to conduct a prospective phase II trial to investigate the efficacy and safety of neoadjuvant tislelizumab plus Disitamab Vedotin followed by adjuvant tislelizumab in patients with high-risk UTUC.

Trial design

This multi-center phase II trial aims to enroll 45 patients with histologically confirmed UTUC at clinical stage cT_2-4N₀M₀ or cT_1-4N_1-2M₀. Neoadjuvant therapy includes 4 cycles of Tislelizumab (200mg for each 3-week cycle) in combination with Disitamab Vedotin (2.0mg/kg for each 3-week cycle). Radical nephroureterectomy was performed if there was no obvious contraindication within 3-6 weeks after the final neoadjuvant therapy administration. Postoperative adjuvant treatment with 8 cycles of tislelizumab will be provided. Primary endpoints: pathological complete response rate. Secondary endpoints: overall survival, local recurrence free survival, distant metastasis free survival, FACT–G.

Clinical trial identification

ChiCTR2300067836.

Legal entity responsible for the study

Y. Bao.

Funding

BeiGene(HongKong)Co., Ltd; RemeGen Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.