Preliminary Clinical Study of Autologous T Cells Modified Chimeric Antigen Receptor (CAR) Targeting PD-L1 and CD80/CD86 (Zeushield Cytotoxic T Lymphocytes) for the Treatment of Recurrent or Refractory Non Small Cell Lung Cancer
Overview
- Phase
- Early Phase 1
- Intervention
- Not specified
- Conditions
- Non-small Cell Lung Cancer
- Sponsor
- Yu Fenglei
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
- Last Updated
- 9 years ago
Overview
Brief Summary
A single-center, open-label pilot study to determine the safety, tolerance and engraftment potential of zeushield cytotoxic T lymphocytes in subjects with PD-L1+ positive non-small cell lung cancer.
Detailed Description
The purpose of this first in human study is to determine the safety and feasibility of Zeushield Cytotoxic T Lymphocytes(Z-CTLs) in patients with relapsed or refractory NSCLC. Z-CTLs therapy is a novel immunotherapy under investigation in which patients have their T-cells (a type of white blood cell) collected and modified in the laboratory, before they are given back to the patient. The T-cells are modified to transform the intracellular signal domain of PD-1 and CTLA-4 to immune activation stimulus signal and transform T cells to a new kind of cancer-killer cells: zeushield cytotoxic T lymphocytes (Z-CTls).
Investigators
Yu Fenglei
Chief of the Thoracic Surgery Department
Second Xiangya Hospital of Central South University
Eligibility Criteria
Inclusion Criteria
- •Men or women aged \>18 years old
- •Subjects are diagnosed as refractory, recurrent ,metastatic, advanced non-small cell lung cancer by histological and cytological methods including specific lesion-targeted brush biopsy, lavage and fine needle aspiration;
- •Have at least one new measurable tumor lesion compared with previous irradiated region
- •Tumor tissues samples confirmed as PD-L1 positive
- •Expected survival≥12 weeks
- •ECOG scored as 0-1 or KPS grading \> 80
- •PLT≥100000/mm3
- •Hb≥9.0g/dL
- •Serum creatinine≤2.5mg/dL，CCR≥50ml/min (renal malfunction defined as CCR\<50ml/min according to Cockroft-Gault formula)
- •ALT and AST≤2.5ULN; for liver metastasis，ALT and AST ≤5ULN
Exclusion Criteria
- •pregnant women or women in lactation
- •active HBV or HCV infection
- •HIV/AIDS infection
- •active infection
- •previously suffered from diseases or concurrent diseases as followed：
- •patients confirmed as severe autoimmune diseases in long-term (over 2 months) need of systemic immune inhibitors (steroid) or as immune-mediated symptomatic diseases including ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus (SLE), autoimmune vasculitis (for example, Wegener's granulomatosis)
- •subjects with previous diagnosis as motor neurone disease caused by autoimmunity
- •subjects previously suffered from toxic epidermal necrolysis (TEN)
- •subjects with any mental diseases including dementia, mental status change that may impinge the understanding and performance of informed consent and related questionnaire
- •subjects with severe, uncontrollable diseases judged by investigators that may hinder them receiving this treatment
Outcomes
Primary Outcomes
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: 8 weeks
Observe and determine the potential adverse events related to the escalating dose infusion of Z-CTLs such as high fever,jaundice, kidney failure and so on.
Secondary Outcomes
- Number of Z-CTLs in peripheral blood samples after infusion(8 weeks)
- Objective response rate (ORR)(2 years)
- Progression free survival (PFS)(2 years)
- Time to tumor progression (TTP)(2 years)
- Overall survival (OS)(2 years)