A Study of RC48-ADC Combined With JS001 For Postoperative Adjuvant Treatment of Upper Tract Urothelial Carcinoma

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of intravenous RC48-ADC combined with JS001 in postoperative adjuvant therapy for HER2-positive upper tract urothelial carcinoma.

Detailed Description
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This is an open-label, single-arm clinical trial to evaluate the efficacy and safety of RC48-ADC, a recombinant humanized anti-HER2 monoclonal antibody-Monomethyl auristatin E (MMAE) conjugate, in combination with JS001, a PD-1 monoclonal antibody, for the postoperative adjuvant treatment of HER2-positive upper tract urothelial carcinoma after radical nephroureterectomy.

Official Title
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An Open-label, Single-arm Study to Evaluate the Efficacy and Safety of RC48-ADC Combined With JS001 in Postoperative Adjuvant Treatment of HER2-positive Upper Tract Urothelial Carcinoma (UTUC)

Conditions
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UTUC, Carcinoma, Upper Tract Urothelial Carcinoma

Intervention / Treatment
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* Drug: RC48-ADC and JS001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent ≥18 years of age Post radical nephro-ureterectomy for upper tract tumour with predominant TCC component-squamoid differentiation or mixed TCC/SCC is permitted. Histologically confirmed TCC staged pT2-pT4 pN0-3 M0 or pTany N1-3 M0 (providing all grossly abnormal nodes are resected). Pathological tissue immunohistochemistry HER2 2 3+ Fit and willing to receive adjuvant therapy with first cycle to be commenced within 30 days of radical nephro-ureterectomy if allocated ECOG(Eastern Cooperative Oncology Group) performance is 0 or 1. Available for long-term follow-up Exclusion Criteria: Evidence of distant metastases Pure adenocarcinoma, squamous cell carcinoma or small cell or other variant histology Un-resected macroscopic nodal disease Concurrent muscle invasive bladder cancer (patients with concurrent Non-muscle invasive bladder cancer (NMIBC) will be eligible) Significant co-morbid conditions that would interfere with administration of protocol treatment Pregnancy; lactating women or women of childbearing potential unwilling or unable to use adequate non-hormonal contraception (male patients should also use contraception if sexually active); Previous malignancy in the last 5 years except for previous NMIBC, adequately controlled non melanoma skin tumours, CIS of cervix or LCIS of breast or localised prostate cancer in patients who have a life expectancy of over 5 years upon trial entry.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RC48-ADC and JS001<br> | Drug: RC48-ADC and JS001<br>* Patients in group will receive 6 x 2 week cycles of JS001 (Toripalimab) 3mg/kg in combination with RC48-ADC (Disitamab Vedotin) 2mg/kg intravenously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival (DFS) | 5-year Disease-free survival | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | 5-year Overall Survival | Patients followed-up for 5 years | 
| Metastasis free survival (MFS) | 5-year Metastasis free survival | Patients are followed up for 5 years |