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

ConditionsUrothelial Carcinoma of the Renal Pelvis and Ureter Neoadjuvant Therapy

Trial statusNot yet recruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorPeking University First Hospital

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

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.
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.

Treatment groups

20 Participants

are divided into 1 treatment group

Group A: Neoadjuvant ADC, immunotherapy and radiotherapy + radical surgeryExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

Pathological complete response rate

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

Time frame

At radical surgery

Secondary outcomes

Objective response rate

Rate of participants achieving complete response or partial response based on imaging assessment using RECIST or protocol-defined criteria.

Time frame

At 2 months after initiation of treatment

Treatment-related adverse events

Incidence and severity of treatment-related adverse events and serious adverse events, graded according to CTCAE.

Time frame

through study completion, an average of 1 year"

Disease-free survival

Time from radical surgery to disease recurrence, progression, or death from any cause

Time frame

Up to 1 year and 3 years after surgery

Local recurrence-free survival

Time from radical surgery to local recurrence, including recurrence in the operative bed or regional retroperitoneal lymph nodes.

Time frame

Up to 3 years after surgery.

Other outcomes

Changes in plasma circulating tumor DNA (ctDNA) levels

Changes in plasma circulating tumor DNA and association with radiographic response, pathological response, recurrence, and survival.Plasma ctDNA will be assessed using a tumor-informed personalized next-generation sequencing (NGS) assay.

Time frame

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

Urinary tumor DNA dynamics

Changes in urinary tumor DNA and association with tumor burden, molecular residual disease, and clinical outcomes

Time frame

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

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Peking University First Hospital

Lead sponsor

Source ClinicalTrials.gov

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