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

China Meitan General Hospital

Status and phase: Unknown; Phase 1

Conditions: Metastatic PD-L1+ Malignant Tumors; Recurrent PD-L1+ Malignant Tumors

Treatments: Biological: autologous CSR T

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02930967

K16-3

Details and patient eligibility

About

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.

Enrollment: 20 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 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;
2. measurable tumors by RECIST1.1 standard;
3. patients are 18 to 70 years old;
4. life expectancy > 3months;
5. KPS ≥70;
6. 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 ;
7. Blood: Hgb ≥ 80 g/L, ANC ≥ 1×10^9/L, PLT ≥ 50×10^9/L;
8. 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

1. patients with a prior history of autoimmune disease or other diseases who need long-term use of systemic hormone drug or immunosuppressive therapy
2. active infection.
3. HIV positive.
4. active hepatitis B virus infection or hepatitis C virus infection.
5. currently enrolled in other study.
6. patients, in the opinion of investigators, may not be eligible or are not able to comply with the study.
7. patients with allergic disease, or are allergic to T cell products or other biological agents used in the study.
8. patients whose tumors have metastasized to bone, or have clinical signs of bone metastasis, such as bone and joint pain.
9. patients with brain metastasis, or have clinical signs of brain metastasis, such as loss of self-consciousness.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

CSR T cells

Experimental group

Description:

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.

Treatment:

Biological: autologous CSR T