Preliminary results of a single-arm, muti-center, prospective clinical study of disitamab vedotin combined with toripalimab and pelvic lymph node dissection for bladder preservation in patients with cT2-4aN0M0 bladder urothelial carcinoma and HER2 expression ≥ 2+ after maximal TURBT.

Abstract

4592 Background: With the evolution of different treatment eras, the clinical complete response (cCR) rate of bladder cancer has been progressively increasing, while the lymph node metastasis rate has still not improved significantly. Particularly, patients with HER2 overexpression are at a higher risk of lymph node metastasis, which poses a major challenge to bladder-sparing therapy for patients with muscle-invasive bladder cancer (MIBC). This study aims to establish a novel bladder-preserving treatment model by combining local therapy enhanced with pelvic lymph node dissection (PLND) and systemic therapy with Disitamab Vedotin and Toripalimab. Methods: Patients with cT2-4aN0M0 MIBC and HER2 expression ≥2+ were enrolled, The primary endpoint was 2-year bladder-intact disease-free survival rate. After maximal transurethral resection of bladder tumor (TURBT), patients received Toripalimab (3mg/kg, Q2W) combined with Disitamab Vedotin (2mg/kg, Q2W) for 6 cycles, followed by TURBT and PLND. Those with cCR or partial response (PR) continued the combined therapy for another 6 cycles. Patients achieving cCR after 12 cycles of combined therapy received maintenance Toripalimab (240mg, Q3W) for 1 year. Non-cCR patients received comprehensive treatment or salvage radical cystectomy(RC). Results: As of December 2025, 21 patients were enrolled, with a median age of 66 years (range: 37–82). The primary endpoint was not yet reached. Efficacy assessment was performed in 14 patients at Week 12: 10/12 (85.8%) achieved cCR, while 1 patient had stable disease (SD) and 1 had progressive disease (PD). Among 10 patients who underwent TURBT and PLND, pathological complete response (pT0N0M0) was achieved in 90.0%, and 1 patient was postoperatively staged as pT0N1M0. Patients with SD or PD underwent RC. All patients experienced treatment-related adverse events (TRAEs) of any grade. The most common TRAEs were pruritus (75.00%), paresthesia (68.75%), and elevated ALT (43.75%), all of which were Grade 1–2. One patient developed a Grade 3 adverse event (AE), which was severe urinary tract infection. No TRAEs of Grade ≥4 were observed. Conclusions: The novel bladder-sparing modality of Disitamab Vedotin combined with Toripalimab plus PLND after maximal TURBT currently demonstrates favorable efficacy and safety. Long-term outcomes warrant further investigation. Clinical trial information: ChiCTR2400081555.