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

NCT07498907 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: LUXUS4.1
• Study Type: interventional
• Target: 192
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Upper Tract Urothelial Carcinoma

Keywords

UTUC; HER2; Disitamab Vedotin; Radiotherapy; Adjuvant Therapy; Cisplatin-Ineligible; Upper Tract Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Overall Survival

  From randomization up to 3 years

• Metastasis-Free Survival

  From randomization up to 3 years

• Local Recurrence-Free Survival

  From randomization up to 3 years

• Bladder Recurrence-Free Survival

  From randomization up to 3 years

• Incidence of Adverse Events

  From first dose through 30 days after completion of study treatment and up to 3 years for follow-up

Study Arms (2)

Disitamab Vedotin Plus Radiotherapy

EXPERIMENTAL

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); Radiation: radiotherapy

Gemcitabine Plus Carboplatin

ACTIVE COMPARATOR

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); Drug: carboplatin

Interventions

Disitamab Vedotin (RC48) DRUG

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.

Disitamab Vedotin Plus Radiotherapy

radiotherapy RADIATION

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.

Disitamab Vedotin Plus Radiotherapy

Gemcitabine (1000 mg/m2) DRUG

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.

Gemcitabine Plus Carboplatin

carboplatin DRUG

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.

Gemcitabine Plus Carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking University First Hospital: lead
• RemeGen Co., Ltd.: collaborator

Study Sites (1)

Peking University First Hospital

Beijing, China

Location

MeSH Terms

Interventions

disitamab vedotin; RC48 antibody; Radiotherapy; Gemcitabine; Carboplatin

Intervention Hierarchy (Ancestors)

Therapeutics; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Central Study Contacts

Xuesong Li, Dr.

CONTACT

010-83572418; pineneedle@sina.com

Zihao Tao, Dr.

CONTACT

taozihao@pku.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2026
• First Posted: March 27, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): March 1, 2034
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)