Clinical trial NCT03060343: Zeushield Cytotoxic T Lymphocytes (Z-CTLs) for Relapsed or Refractory Non Small Cell Lung Cancer (NSCLC)
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Non-small Cell Lung Cancer
Lead sponsor: Second Xiangya Hospital of Central South University
Sponsor class: OTHER
Collaborators: name: Hunan Zhaotai Yongren Medical Innovation Co. Ltd.
name: Hunan Yongren Medical Innovation Co. Ltd.
First posted: 2017-02-23
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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
* 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

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: 8 weeks
Secondary outcomes:
measure: Number of Z-CTLs in peripheral blood samples after infusion
timeFrame: 8 weeks
measure: Objective response rate (ORR)
timeFrame: 2 years
measure: Progression free survival (PFS)
timeFrame: 2 years
measure: Time to tumor progression (TTP)
timeFrame: 2 years
measure: Overall survival (OS)
timeFrame: 2 years
Other outcomes:
Locations:
city: Changsha
country: China
facility: Second Xiangya Hospital of Central South University
state: Hunan
Study officials:
affiliation: Central South University
name: Yu Fenglei, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hunan Zhaotai Yongren Medical Innovation Co. Ltd.
name: Li Peng, PhD
role: PRINCIPAL_INVESTIGATOR
References: