Preliminary results of a phase II study to evaluate the efficacy and safety of disitamab vedotin (RC48-ADC) in combination with radiotherapy for adjuvant therapy in upper tract urothelial carcinoma.

e16583 Background: Although postoperative platinum-based adjuvant chemotherapy improves disease-free survival (DFS), many upper tract urothelial carcinoma (UTUC) patients (pts) were ineligible for cisplatin after radical nephroureterectomy (RNU). UTUCs did not seem to benefit from adjuvant immunotherapy. Previous evidence demonstrated adjuvant radiotherapy improvesd cancer-specific survival in HR UTUCs. Further exploration of alternative adjuvant treatment strategies is needed. This study aims to evaluate the therapeutic potential of RC48-ADC in combination with radiotherapy in HER2 overexpressing UTUCs. Methods: This is an open-label, phase II, non-randomised study to evaluate the efficacy and safety of disitamab vedotin (RC48-ADC), a humanized anti-HER2 antibody, in combination with radiotherapy as a novel adjuvant therapy strategy in UTUC. We recruited cisplatin-intolerant pts with HER2-overexpressing (Immunohistochemistry, IHC 2+, 3+) UTUC after nephroureterectomy staged as pT2N0M0 with high-grade/multifocal disease/positive surgical margin, pT3-4 N0 M0 or pTany N1-2 M0. Pts who declined any adjuvant therapy were assigned to the surveillance group. Pts in adjuvant therapy group received RC48-ADC (2.0 mg/kg D1 Q2W, 6 months) and radiotherapy (45-50Gy/25f/5w, lymphatic drainage regions; 62.5Gy/25f/5w, enlarged lymphnode). The therapy was initiated within 90 days of surgery. The primary end point was DFS. Secondary end points were overall survival (OS), metastasis-free survival (MFS), local-recurrence free survival (LRFS) and safety. Exploratory endpoints aimed to assess the correlation between biomarkers in blood, and urine with treatment efficacy. Results: As of December 2024, 31 pts (15 males and 16 females) out of the planned 60 pts have been enrolled in the study with median age of 68 years. 15 pts were assigned to adjuvant therapy group and 16 in surveillance. In therapy group, 3 pts completed adjuvant therapy, one patient withdrew the trial because of cardiovascular disease, and remaining pts were undergoing treatment. At a median follow-up of 6 months, no recurrences were observed in the therapy group, while 5 pts in surveillance experienced recurrence. As of now, the most common TRAEs were abdominal pain (13.3%), rash (13.3%), WBC decreased (13.3%), ALT/AST increased (13.3%), GGT increased (6.7%), fatigue (6.7%), platelet count decreased (6.7%). Grade ≥ 3 TRAE was observed in 6.7% (1/15) pts, one patient experienced grade 3 gastrointestinal hemorrhage. Conclusions: This study is the first to evaluate the efficacy and safety in adjuvant treatment of ADC plus radiotherapy in UTUCs. The combination of RC48-ADC and radiotherapy as a new adjuvant therapy demonstrated a tolerable safety profile in pts with HER2-overexpressing UTUC. Clinical trial information: NCT06210490 .