Effectiveness and safety of RC48-ADC in combination with toripalimab as neoadjuvant treatment in HER2-positive muscular invasive urothelial bladder cancer patients.

710 Background: Bladder cancer with high expression of human epidermal growth factor receptor 2 (HER2) is associated with pathological malignancy and poor prognosis. For patients with muscle-invasive bladder cancer that can be curative resected, the standard treatment is radical cystectomy and pelvic lymph node dissection following neoadjuvant chemotherapy (NAC). However, NAC is inefficient, and many patients cannot tolerate its adverse reactions. Therefore, a novel and safe strategy for these patients is needed after NAC. Methods: In this study, patients with muscle-invasive bladder cancer (MIBC) diagnosed with cT2a-4aN0M0 who were HER2 positive (HER2 IHC1+, 2+, or 3+) and intolerant to platinum underwent transurethral resection of bladder tumor (TURBT). This was followed by 4 cycles of toripalimab (200 mg, intravenous, D1, Q2W) combined with disitamab vedotin (2 mg/kg, intravenous, D1, Q2W) as neoadjuvant therapy. For patients who requested bladder preservation, we performed Re-cTURBT or multipoint biopsy to verify the status of residual tumors in the bladder. The primary endpoint was pathological complete response (pCR). Secondary endpoints included objective response rate (ORR), overall survival (OS), and safety. Results: A total of 28 patients were enrolled from April 2023 to Jun 2024 in our hospital. The median age was 68 years (range: 55-82). By the data cut-off in June 2024, 16 patients (57.1%) achieved clinical complete response (cCR). Among those who achieved cCR, the primary endpoint of pCR was 93.7% (15/16). The median follow-up time was 11.8 months. The median OS was not reached, ORR was 96.4% (27/28). Regarding safety, treatment-related adverse events (TRAEs) of any grade occurred in 21 patients (75%). The most common TRAEs were fatigue (68.3%), itching (57.5%), poor appetite (51.2%), alopecia (33.3%), and diarrhea (16.7%), all of which are grade 1-2. Grade 3 TRAE occurred in 4 patients (14.3%), with one patient experiencing cardiac tachycardia (3.5%) and 3 patients having hepatic dysfunction (10.7%). No grade 4 and 5 TRAEs were observed. Conclusions: Disitamab vedotin (RC48-ADC) combined with toripalimab as neoadjuvant treatment has shown excellent effectiveness and safety in curative resectable MIBC patients with HER2 positive. Those who achieved cCR and underwent Re-cTURBT and multipoint biopsy in bladder had an excellent pCR.