A clinical trial evaluating the efficacy and safety of disitamab vedotin plus tislelizumab combined with re-TURBT in the treatment of HER-2-high expression (2+-3+) non-muscle invasive bladder cancer at high-risk and very high-risk.

TPS895 Background: Current studies indicate that the combination of Disitamab Vedotin and PD-1 inhibitors can enhance the efficacy of systemic therapy in patients with HER2-positive urothelial carcinoma, with an acceptable safety profile. However, the evidence supporting its use in high-risk and very high-risk NMIBC remains limited. And several clinical guidelines recommend a re-TURBT for high-risk NMIBC patients, as it has been shown to significantly reduce the 5-year recurrence and progression rates.Therefore, this study aims to evaluate the efficacy and safety of the triplet regimen of Disitamab Vedotin, Tislelizumab (a PD-1 inhibitor), and re-TURBT in patients with HER2 IHC 2+ or 3+ high-risk and very high-risk NMIBC. Methods: Patients diagnosed with high-risk and very high-risk NMIBC, based on medical history, clinical presentation, imaging examinations (such as MRI with plain and enhanced scanning), and transurethral resection for tissue pathological biopsy, are included in the "case screening process".After excluding surgical contraindications, TURBT is performed; postoperative tissue pathological examination confirms NMIBC, and patients with immunohistochemical results of HER2 as 3+ or 2+ enter further screening. Referring to the AUA guidelines, high-risk and very high-risk NMIBC are included in subsequent analysis, where those who meet the inclusion criteria of this study, excluding the exclusion criteria, and who have recovered well after the initial TURBt and are assessed to be able to complete a second TURBT within six weeks are considered as the final candidates for enrollment.Eligible patients for single-arm enrollment (N=40) will receive Tislelizumab (200mg) + Disitamab Vedotin (120mg for weight ≤60Kg or 2.0mg/Kg for weight ≥60Kg) the day after the initial TURBT, to be repeated every 3 weeks (Q3W). Patients are also scheduled to undergo a second TURBT within 6 weeks, and after the surgery, they will continue with three more courses of Tislelizumab + Disitamab Vedotin (Q3W) until the end of the 3-year follow-up period. The primary endpoint for evaluation in this study phase is the 1-year event-free survival rate (EFS),which is defined as the possibility of patients have not experienced any events for at least 12 months after receiving treatment, including death, disease progression, switch to chemotherapy, addition of other treatments, fatal or intolerable side effects, etc. Clinical trial information: NCT06630871 .