Clinical trial NCT02930967: Chimeric Switch Receptor Modified T Cells for Patients With PD-L1+ Recurrent or Metastatic Malignant Tumors
Official title: A Safety and Efficacy Study of Chimeric Switch Receptor Modified T Cells in Patients With Recurrent or Metastatic Malignant Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Recurrent PD-L1+ Malignant Tumors
Metastatic PD-L1+ Malignant Tumors
Lead sponsor: China Meitan General Hospital
Sponsor class: OTHER
Collaborators: name: Marino Biotechnology Co., Ltd.
First posted: 2016-10-12
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Safety as assessed by incidents of treatment related adverse events as assessed by CTCAE V4.0.
timeFrame: 2 years
Secondary outcomes:
measure: treatment response rate of CSR T cell infusion
timeFrame: 4 weeks
measure: overall survival rate
timeFrame: 2 years
measure: progression-free survival
timeFrame: 6 months
measure: proliferation of CSR T cells in patients
timeFrame: 2 years
measure: Persistence of CSR T cells in patients
timeFrame: 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: China Meitan General Hospital
Study officials:
affiliation: China Meitan General Hospital
name: Jinwen Sun, MD
role: PRINCIPAL_INVESTIGATOR
References: