Chimeric Switch Receptor Modified T Cells for Patients With PD-L1+ Recurrent or Metastatic Malignant Tumors

Study Overview
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Brief Summary
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A Chimeric Switch Receptor, which was constructed by fusing the PD1 extracellular ligand binding domain to the CD28 intracellular costimulatory domain, was designed to target PD-L 1 positive tumors . In this single-arm, open-label, one center, dose escalation clinical study, the main purpose is to determine the safety and efficacy of infusion of autologous Chimeric Switch Receptor modified T cells (CSR T) in adult patients with PD-L1 positive, recurrent or metastatic malignant tumors.

Official Title
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A Safety and Efficacy Study of Chimeric Switch Receptor Modified T Cells in Patients With Recurrent or Metastatic Malignant Tumors

Conditions
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Recurrent PD-L1+ Malignant Tumors, Metastatic PD-L1+ Malignant Tumors

Intervention / Treatment
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* Biological: autologous CSR T


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with PD-L1 positive, recurrent or metastatic malignant tumors , including but not limited to pancreatic cancer, renal cancer, colorectal cancer, lymphoma, breast cancer and lung cancer; measurable tumors by RECIST1.1 standard; patients are 18 to 70 years old; life expectancy > 3months; KPS ≥70; satisfactory major organ functions: adequate heart function with LVEF≥50%; no obvious abnormities in ECG; pulse oximetry ≥ 90%; cockcroft-gault creatinine clearance≥40 ml/min; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3ULN; Bilirubin ≤2.0 mg/dl ; Blood: Hgb ≥ 80 g/L, ANC ≥ 1×10^9/L, PLT ≥ 50×10^9/L; women of reproductive potential must have a negative pregnancy test. Male and female of reproductive potential must agree to use birth control during the study and one year post study. Exclusion Criteria: patients with a prior history of autoimmune disease or other diseases who need long-term use of systemic hormone drug or immunosuppressive therapy active infection. HIV positive. active hepatitis B virus infection or hepatitis C virus infection. currently enrolled in other study. patients, in the opinion of investigators, may not be eligible or are not able to comply with the study. patients with allergic disease, or are allergic to T cell products or other biological agents used in the study. patients whose tumors have metastasized to bone, or have clinical signs of bone metastasis, such as bone and joint pain. patients with brain metastasis, or have clinical signs of brain metastasis, such as loss of self-consciousness.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: CSR T cells<br>A dose escalation clinical study aimed to assess the safety and efficacy of CSR T cells in patients with PD-L1 positive tumors. CSR T dosage ranging from: 5×10^4 /kg to 1×10^7 /kg will be tested. | Biological: autologous CSR T<br>* Patients will be received a three-day regimen of chemotherapy consisting of cyclophosphamide aimed to deplete the lymphocytes. 1 to 4 days after lymphodepletion, a prescribed dose of CSR T cells will be intravenously infused to patient in a three-day split-dose regimen (day0,10%; day1, 30%; day2, 60%).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety as assessed by incidents of treatment related adverse events as assessed by CTCAE V4.0. | safety of infusion of autologous CSR T cells with cyclophosphamide as lymphodepleting chemotherapy | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| treatment response rate of CSR T cell infusion | defined as the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD). | 4 weeks | 
| overall survival rate |  | 2 years | 
| progression-free survival |  | 6 months | 
| proliferation of CSR T cells in patients |  | 2 years | 
| Persistence of CSR T cells in patients |  | 2 years |