A Phase I Clinical Study of SHR-2005 Intravesical Instillation in the Treatment of High-risk Non-muscle Invasive Bladder Cancer (NMIBC)

Study Overview
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Brief Summary
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This study is an open-label, multicenter Phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics and efficacy of SHR-2005 for Intravesical perfusion in patients with high-risk non-muscle invasive bladder cancer.

Official Title
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A Phase I Clinical Study of SHR-2005 Intravesical Instillation in the Treatment of High-risk Non-muscle Invasive Bladder Cancer (NMIBC)

Conditions
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High-risk Non-muscle Invasive Bladder Cancer

Intervention / Treatment
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* Drug: SHR-2005


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must voluntarily agree to participate in the trial and sign a written informed consent form; ≥18 years of age, either sex; Previous pathological biopsy was diagnosed as high-risk NMIBC ; ECOG performance status of 0-1; Life expectancy ≥ 2 years; Adequate bone marrow and organ function. Exclusion Criteria: Received TURBT or other surgical treatment or radiotherapy for bladder lesions within 2 weeks before the first administration; Patients who were receiving treatment in other clinical trials or less than 4 weeks from the end of the first administration in this study; History of serious cardiovascular and cerebrovascular diseases; Severe infection within 2 weeks prior to the first dose; Adverse reactions of previous anti-tumor treatment have not recovered to Grade ≤ 1 per NCI-CTCAE v5.0; Oversize surgery or severe trauma within 4 weeks before the first use of research drugs; Previously received any TNFR agonist antibody therapy, such as OX40, CD137, CD27, CD357 antibodies.

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
Interventional Model Description: This study is an open-label, multicenter Phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics and efficacy of SHR-2005 for Intravesical perfusion in patients with high-risk non-muscle invasive bladder cancer.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-2005<br>Only one arm with SHR-2005 | Drug: SHR-2005<br>* In dose Escalation: Five dose levels are preset. The administration cycle included 6 times of induction perfusion period and 15 times of maintenance perfusion period. In indication Expansion: Indications will be selected to evaluate preliminary efficacy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose limiting toxicities (DLTs) |  | From Day 1 to Day 21 | 
| Maximum tolerated dose (MTD) |  | From Day 1 to Day 21 | 
| Incidence and severity of adverse events (AEs) ([CTCAE] v5.0) |  | From Day 1 to 90 days after last dose | 
| RP2D（Recommended Phase 2 dose） |  | From Day 1 to 90 days after last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameter: Tmax of SHR-2005 | Time to maximum concentration of SHR-2005 | approximately 24 months | 
| PK parameter: Cmax of SHR-2005 | Maximum concentration of SHR-2005 | approximately 24 months | 
| PK parameter: AUC0-∞ of SHR-2005 | area under the concentration-time curve from time 0 to infinity of SHR-2005 | approximately 24 months | 
| Immunogenicity of SHR-2005 | Anti- SHR-2005 antibody (ADA) | approximately 24 months | 
| Duration of response (DoR) | Evaluated using RECIST 1.1 | approximately within 36 months | 
| Disease control rate (DCR) | Evaluated using RECIST 1.1 | approximately within 36 months | 
| Progression-free survival (PFS) | Evaluated using RECIST 1.1 | approximately within 36 months | 
| Amount_recovered and Percent_recovered | The Amount _ recovered and Percent _ recovered of SHR-2005 in urine after intravesical instillation. | approximately 24 months |