Disitamab Vedotin Plus Radiotherapy for Adjuvant Treatment of HER2-Expressing Cisplatin-Ineligible Upper Tract Urothelial Carcinoma (LUXUS41)

A Randomized, Prospective, Multicenter, Phase II Study of Disitamab Vedotin Plus Radiotherapy as Adjuvant Treatment for HER2-Expressing Cisplatin-Ineligible Upper Tract Urothelial Carcinoma

This randomized, open-label, multicenter phase II 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.

Study Overview

• Status: Not yet recruiting
• Conditions: Upper Tract Urothelial Carcinoma
• Intervention / Treatment: Drug: Disitamab Vedotin (RC48); Radiation: radiotherapy; Drug: Gemcitabine (1000 mg/m2); Drug: carboplatin

• Study Type: Interventional
• Enrollment (Estimated): 192
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xuesong Li, Dr.; Phone Number: 010-83572418; Email: pineneedle@sina.com
• Study Contact Backup: Name: Zihao Tao, Dr.; Email: taozihao@pku.edu.cn

Study Locations

• China
  • Beijing, China
    • Peking University First Hospital
    • Contact: Xuesong Li, Dr.; Phone Number: 010-83572418; Email: pineneedle@sina.com
    • Contact: Qi Tang, Dr.; Email: drtangq@bjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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+).
• Cisplatin-ineligible, defined as meeting at least one of the following criteria: ECOG performance status 2; creatinine clearance <60 mL/min; CTCAE grade 2 or higher hearing loss; CTCAE grade 2 or higher peripheral neuropathy; or New York Heart Association (NYHA) class III heart failure.
• Adequate organ function.
• Expected survival of at least 6 months.

Exclusion Criteria:

• 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.
• Not adequately recovered from surgery.
• Pregnant or breastfeeding women.
• Any other condition that, in the investigator's judgment, makes the patient unsuitable for participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Disitamab Vedotin Plus Radiotherapy; Participants in this arm will receive disitamab vedotin plus radiotherapy as adjuvant treatment after radical surgery for HER2-expressing,cisplatin-ineligible upper tract urothelial carcinoma.	Drug: Disitamab Vedotin (RC48); Disitamab vedotin 2.0 mg/kg (maximum 120 mg) will be administered intravenously every 2 weeks for 12 cycles as adjuvant treatment after radical surgery.; Radiation: radiotherapy; Adjuvant 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.
Active Comparator: Gemcitabine Plus Carboplatin; Participants in this arm will receive gemcitabine plus carboplatin as adjuvant treatment after radical surgery for HER2-expressing cisplatin-ineligible upper tract urothelial carcinoma.	Drug: Gemcitabine (1000 mg/m2); Gemcitabine 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.; Drug: carboplatin; Carboplatin 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From randomization up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival (OS) is defined as the time from randomization to death from any cause.	From randomization up to 3 years
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.	From randomization up to 3 years
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.	From randomization up to 3 years
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	From randomization up to 3 years
Incidence of Adverse Events	Safety will be evaluated based on the incidence, type, severity, and attribution of adverse events during study treatment and follow-up.	From first dose through 30 days after completion of study treatment and up to 3 years for follow-up
Patient-Reported Quality of Life	Patient-reported quality of life will be assessed using validated quality-of-life questionnaires during treatment and follow-up.	Baseline through 3 years

Collaborators and Investigators

• Sponsor: Peking University First Hospital
• Collaborators: RemeGen Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): March 1, 2034

Study Registration Dates

• First Submitted: March 23, 2026
• First Submitted That Met QC Criteria: March 23, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: HER2; Radiotherapy; UTUC; Adjuvant Therapy; Cisplatin-Ineligible; Upper Tract Urothelial Carcinoma; Disitamab Vedotin
• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Gemcitabine; Carboplatin; disitamab vedotin; Radiotherapy; RC48 antibody
• Other Study ID Numbers: LUXUS4.1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No