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NCT07720921

PHASE2

Neoadjuvant Disitamab Vedotin, Toripalimab, and Radiotherapy for High-risk UTUC ( LUXUS07.1 )

Sponsor: Peking University First Hospital

View on ClinicalTrials.gov

Summary

This is an open-label, single-arm, single-cohort, prospective clinical study evaluating neoadjuvant antibody-drug conjugate therapy combined with immunotherapy and sequential radiotherapy followed by radical surgery in patients with high-risk upper tract urothelial carcinoma (UTUC). Eligible patients will receive neoadjuvant disitamab vedotin (RC48) plus toripalimab, followed by response-guided neoadjuvant radiotherapy and radical nephroureterectomy with bladder cuff excision. The study will assess the safety, feasibility, and preliminary antitumor activity of this multimodal neoadjuvant strategy, with pathological complete response rate as the primary endpoint.

Official title: Efficacy and Safety of Neoadjuvant Disitamab Vedotin, Toripalimab, and Radiotherapy for High-risk Upper Tract Urothelial Carcinoma: A Single-arm, Open Label, Prospective Cohort Study

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

Start Date

2026-08-01

Completion Date

2029-08-01

Last Updated

2026-07-22

Healthy Volunteers

Conditions

Urothelial Carcinoma of the Renal Pelvis and Ureter Neoadjuvant Therapy

Interventions

RADIATION

Neoadjuvant radiotherapy

Patients with a clear pathological diagnosis of high-risk UTUC were treated with a short course of 5 days of naSBRT: radiotherapy irradiation was directed to the primary lesion on the affected side and to the lymphatic drainage area, with a dose of 25 Gy (5 Gy\*5 days).The safety of the neoadjuvant radiotherapy dose and regimen can be evaluated by metrological ramping in the initial 5 patients, with subsequent patients following the optimal dose from ramping.

DRUG

ADC + PD1 monoclonal antibody

Participants will receive disitamab vedotin (RC48) 2.0 mg/kg intravenously every 2 weeks, on day 1 of each 14-day cycle, for up to 6 cycles, with a maximum safe dose of 120 mg. Participants will also receive toripalimab 3.0 mg/kg intravenously every 2 weeks, on day 1 of each 14-day cycle, for up to 6 cycles. A safety run-in phase will evaluate dose-limiting toxicities. If ≥2 of the first 6 patients experience DLT, the ADC schedule will be adjusted from every 2 weeks for 6 cycles to every 3 weeks for 4 cycles, with continued safety and efficacy monitoring.

Inclusion Criteria: * Age ≥18 years, male or female. * Imaging evaluation before treatment excludes distant organ metastasis or other concurrent malignancy and suggests resectable high-risk UTUC. * Completed pathological biopsy with a clear pathological diagnosis : including puncture biopsy, ureteroscopy and urine cytology, at least one of which is clearly diagnosed as uroepithelial carcinoma, which may include no more than 50% or more proportion of squamous, adenoid, sarcomatoid differentiation and other special differentiation types; * High-risk features, including muscle-invasive disease, high-grade tumor, multifocal disease, tumor diameter ≥2 cm, hydronephrosis, or regional lymph node involvement. * HER2 expression by immunohistochemistry 1+ to 3+; PD-L1 expression not restricted. * Have the willingness to undergo radical surgical treatment and perioperative adjuvant treatment, have good compliance, and be able to co-operate with the treatment and follow-up plan specified by the clinician; * Postoperative life expectancy of at least 6 months; ECOG score ≤ 2. Exclusion Criteria: * Distant metastases or other malignant neoplastic diseases combined with other malignant neoplasms in the same period had been detected at the time of surgery, or the present was a progression after palliative resection of previous epithelial carcinoma of the urothelium; * History of pelvic and abdominal radiotherapy; history of inflammatory bowel disease; history of systemic chemotherapy; * Pregnant women or breastfeeding women; or women of childbearing potential who are not using reliable contraception; * The presence of active infections in those with pre-existing or coexisting haemorrhagic disorders * clinically significant cardiac disease (e.g., hypertension controlled with medications, unstable angina, New York Heart Association (NYHA) class ≥II congestive heart failure, unstable symptomatic arrhythmias, or class ≥II peripheral vascular disease); * Psychological, familial, and social factors leading to lack of informed consent.

Locations (1)

Departmeng of Urology, Peking University First Hospita

Beijing, Beijing Municipality, China