Metastatic PD-L1+ Malignant Tumors, Recurrent PD-L1+ Malignant Tumors
Conditions
Brief summary
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.
Interventions
BIOLOGICALautologous CSR T
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%).
Sponsors
Marino Biotechnology Co., Ltd.
China Meitan General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety as assessed by incidents of treatment related adverse events as assessed by CTCAE V4.0. | 2 years | safety of infusion of autologous CSR T cells with cyclophosphamide as lymphodepleting chemotherapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| treatment response rate of CSR T cell infusion | 4 weeks | defined as the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD). |
| 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 | — |
Countries
China
Contacts
Primary ContactShidong Wei, MD
Outcome results
None listed