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

NCT07720921 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: LUXUS 7.1LUXUS
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Neoadjuvant Therapy; Urothelial Carcinoma of the Renal Pelvis and Ureter

Keywords

UTUC; neoadjuvant radiotherapy; neoadjuvant immunotherapy; neoadjuvant Antibody-Drug Conjugate; prospective cohort; disitamab vedotin

Outcome Measures

Primary Outcomes (1)

• Pathological complete response rate

  Proportion of participants with no residual viable tumor in the surgical specimen, as assessed by pathological evaluation.

  At radical surgery

Secondary Outcomes (6)

• Objective response rate

  At 2 months after initiation of treatment

• Treatment-related adverse events

  through study completion, an average of 1 year"

• Disease-free survival

  Up to 1 year and 3 years after surgery

• Local recurrence-free survival

  Up to 3 years after surgery.

• Metastasis-free survival

  Up to 3 years after surgery.

Other Outcomes (2)

• Changes in plasma circulating tumor DNA (ctDNA) levels

  Baseline, 2 months after the first dose, and within 2 weeks after surgery

• Urinary tumor DNA dynamics

  Baseline, interim assessment during neoadjuvant treatment,post-radiotherapy assessment.

Study Arms (1)

Neoadjuvant ADC, immunotherapy and radiotherapy + radical surgery

EXPERIMENTAL

Participants in this single cohort will receive neoadjuvant disitamab vedotin (RC48) plus toripalimab, followed by response-guided targeted-volume radiotherapy and radical nephroureterectomy with bladder cuff excision. Surgery is planned approximately 2-4 weeks after completion of the last neoadjuvant treatment, if the patient's clinical condition permits.

Radiation: Neoadjuvant radiotherapy; Drug: ADC + PD1 monoclonal antibody

Interventions

Neoadjuvant radiotherapy RADIATION

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.

Neoadjuvant ADC, immunotherapy and radiotherapy + radical surgery

ADC + PD1 monoclonal antibody DRUG

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.

Neoadjuvant ADC, immunotherapy and radiotherapy + radical surgery

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking University First Hospital: lead

Study Sites (1)

Departmeng of Urology, Peking University First Hospita

Beijing, Beijing Municipality, China

Location

MeSH Terms

Interventions

Neoadjuvant Therapy; arginine decarboxylase

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics

Central Study Contacts

ZUO WEI, Dr

CONTACT

+8618811650832; vivian19980814@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Department of Urology

Study Record Dates

• First Submitted: June 17, 2026
• First Posted: July 22, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2029
• Last Updated: July 22, 2026

Record last verified: 2026-07

Locations

CN (1)