Zeushield Cytotoxic T Lymphocytes (Z-CTLs) for Relapsed or Refractory Non Small Cell Lung Cancer (NSCLC)

Yu Fenglei

Status and phase

Unknown

Early Phase 1

Conditions

Non-small Cell Lung Cancer

Treatments

Biological: Zeushield Cytotoxic T Lymphocytes

Study type

Interventional

Funder types

Other

Identifiers

NCT03060343

Z-NSCLC-01

Details and patient eligibility

About

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.

Full 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).

Enrollment

10 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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
Serum TBiL≤3.0mg/dL, TBiL≤2.5ULN
PT: INR < 1.7 or extended PT to normal value < 4s
Adequate venous access for apheresis or venous blood collection, and no other contraindication of blood cell separation
Patients with willingness to be in this study and able to provide informed consent
Capable of receiving treatment and follow up, included subjects are required to receive treatment in the enrolled centre
Women of childbearing age are required to take acceptable measures to minimize the possibility of pregnancy during whole session. Women of childbearing age must have negative results of serum or urine tests within 24 hours prior to infusion. Women subjects must not be in lactation;

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
subjects with previously active malignant tumors including basal or squamous skin cancer, superficial bladder cancer, and in situ breast carcinoma within 5 years who had been completely cured without the need of follow-up treatment are not excluded.
during ongoing treatment using systemic steroid or steroid inhalants
subjects with unstable or active peptic ulcer or alimentary tract hemorrhage
subjects with previous organ transplantation or ready for organ transplantation
subjects in need of anticoagulant therapy treatment (warfarin or heparin)
subjects judged by investigators as not appropriate for this study