This randomized, open-label, multicenter phase III study is designed to compare disitamab vedotin plus radiotherapy with gemcitabine plus carboplatin as adjuvant treatment in patients with HER2-expressing upper tract urothelial carcinoma after radical nephroureterectomy (RNU). Eligible patients must have postoperative pathologic stage pT3-pT4N0M0 or pTanyN+M0, HER2 expression defined as immunohistochemistry (IHC) 1+, 2+, or 3+, and be cisplatin-ineligible. Patients will be randomized in a 2:1 ratio to receive disitamab vedotin plus radiotherapy or gemcitabine plus carboplatin. The primary endpoint is 3-year disease-free survival. Secondary endpoints include overall survival, metastasis-free survival, local recurrence-free survival, bladder recurrence-free survival, incidence of adverse events, and patient-reported quality of life.
Aged 18 years or older.
Histologically confirmed upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU).
Postoperative pathologic stage pT3-pT4N0M0 or pTanyN+M0.
HER2 expression confirmed by immunohistochemistry (IHC 1+, 2+, or 3+).
History of other active malignancies, except for adequately treated malignancies with low risk of recurrence.
Prior systemic antitumor therapy before study treatment, or unresolved toxicities from prior therapy.
Known hypersensitivity to disitamab vedotin, related agents, or any component of the study treatment.
Severe active infection.
Parallel
Disitamab Vedotin (RC48)
DrugDisitamab vedotin 2.0 mg/kg (maximum 120 mg) will be administered intravenously every 2 weeks for 12 cycles as adjuvant treatment after radical surgery.
radiotherapy
RadiationAdjuvant radiotherapy will be delivered to the regional lymphatic drainage area at 45-50 Gy in 25 fractions over 5 weeks. Suspicious lymph nodes will receive 62.5 Gy in 25 fractions over 5 weeks.
Gemcitabine (1000 mg/m2)
DrugGemcitabine 1000 mg/m² will be administered on Days 1 and 8 of each 21-day cycle for 4 to 6 cycles as adjuvant treatment after radical surgery.
carboplatin
DrugCarboplatin will be administered intravenously on Day 1 of each 21-day cycle at a target AUC of 4.5 to 5 for 4 to 6 cycles as adjuvant treatment after radical surgery.
3-Year Disease-Free Survival
Disease-free survival (DFS) is defined as the time from randomization to first recurrence in the tumor bed, first metastasis, or death from any cause, whichever occurs first.
Overall Survival
Overall survival (OS) is defined as the time from randomization to death from any cause.
Metastasis-Free Survival
Metastasis-free survival (MFS) is defined as the time from randomization to first documented distant metastasis or death from any cause, whichever occurs first.
Local Recurrence-Free Survival
Local recurrence-free survival (LRFS) is defined as the time from randomization to first documented locoregional recurrence in the tumor bed or regional lymph nodes, or death from any cause, whichever occurs first.
Bladder Recurrence-Free Survival
Bladder recurrence-free survival (BRFS) is defined as the time from randomization to first documented bladder urothelial recurrence or death from any cause, whichever occurs first
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Peking University First Hospital
Lead sponsor
RemeGen Co., Ltd.
Collaborator
