Study of Autologous CIK Cell Immunotherapy Combination With PD-1 Inhibitor and Chemotherapy in the Advanced NSCLC

Study Overview
=================
Brief Summary
-----------------
This prospective, unicentric, open-labe phase I study is to evaluate the effects of autologous cytokine-induced killer cell immunotherapy combination with PD-1 inhibitor and chemotherapy in the first-line treatment of IIIB/IIIC/IV non-small cell lung cancer.

Detailed Description
-----------------
In the non-squamous NSCLC, patients received sintilimab Injection (PD-1 inhibitor) 200mg, d1; pemetrexed injection 500mg/m2, d1; carboplatin injection AUC 5, d1; CIK cells venous re-transfusion >=1x10^10, d14; Q3W, for 4 cycles. Then sintilimab and pemetrexed maintenance treatment for 2 years. In the squamous NSCLC, patients received sintilimab Injection (PD-1 inhibitor) 200mg, d1; liposome paclitaxel injection 135mg/m2, d1; carboplatin injection AUC 5, d1; CIK cells venous re-transfusion >=1x10^10, d14; Q3W, for 4 cycles. Then sintilimab maintenance treatment for 2 years.

Official Title
-----------------
Phase I Clinical Study of Autologous CIK Cell Immunotherapy Combination With PD-1 Inhibitor and Chemotherapy in the First-line Treatment of IIIB/IIIC/IV Non-Small Cell Lung Cancer

Conditions
-----------------
Non-small Cell Lung Cancer, First-line Treatment

Intervention / Treatment
-----------------
* Biological: CIK cell
* Biological: Sintilimab Injection
* Drug: Pemetrexed
* Drug: Liposome paclitaxel
* Drug: Carboplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects who must meet all the following criteria should be selected: Agreeing to participate in this study and signing a written informed consent. Male or female,from 18 to 75 years (including 18 and 75 years). The life expectancy will be longer than 3 months and can be followed up. Patients with stage IIIB/IIIC/IV NSCLC were confirmed by histological /cytological and imaging examinations. According to RECIST 1.1 standard, there will be at least one measurable lesion. Initial medical treattment.Patients with adenocarcinoma need wild type of EGFR gene and ALK fusion gene negative to be included in this study. ECOG score will be 0 or 1 within 7 days before randomization. Within 14 days before the start of treatment, the results of laboratory test of blood routine, liver, kidney function and hormone levels must be met the following criteria: White blood cells: more than 3.0 × 109/L; Platelets: more than 100 × 109/L; Neutrophils: more than 1.5 × 109/L; Hemoglobin: more than 80g/L; Serum glutamate pyruvate transaminase: less than 2.5 folds of the upper normal limit (ULN); Serum glutamic-oxal (o) acetic transaminase: less than 2.5 × ULN; Serum bilirubin: less than 1.25 × ULN; Serum creatinine: less than 1.25 × ULN. Cortisol and thyroid function will be in the normal range. The toxicity and side effects of previous chemotherapy will must be alleviated to grade 1 or below (except hair loss). Female subjects must take effective contraceptive measures throughout the study period; serum or urine pregnancy test results must be negative during screening and the whole study period. Male subjects should take effective contraceptive measures from the beginning of treatment to within 6 months after the end of treatment. Exclusion Criteria: Subjects who meet any of the following criteria could not participate in this study: Adenocarcinoma subjects with EGFR sensitive mutation or ALK translocation; molecular detection of EGFR-sensitive mutations or ALK translocations is not required in squamous carcinoma patients. NSCLC that had received chemotherapy in the past. Other malignant tumors needed treatment within five years. Allogeneic tissue/organ transplantation. Participating in research drug therapy within 4 weeks before the first administration of the trial. Systemic glucocorticoid therapy or any other form of immunosuppressive therapy (except glucocorticoid preconditioned with docetaxel) is being administered within 3 days before the first administration of the experimental therapy. Received anti-tumor monoclonal antibody (mAb), chemotherapy, targeted small molecule therapy or major surgery within 4 weeks before the first use of the drug; received chest radiotherapy greater than 30 Gy within 6 months before the first use of the drug; and received chest radiotherapy with 30 Gy or less within 1 month before the first use of the drug. Previous treatment with PD-1/PD-L1 antibodies. Over the past two years, patients with active autoimmune diseases requiring systemic treatment, such as the use of corticosteroids, or immunosuppressants. Substitution therapy (such as thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary dysfunction) is not a systemic treatment. Patients with congenital or acquired immunodeficiency (e.g. HIV-infected persons), active hepatitis B (HBV-DNA > 10^3 copies/ml) or hepatitis C (hepatitis C antibody positive), and HCV-RNA higher than the detection limit of the analytical method. Subjects with active central nervous system (CNS) metastases and/or cancerous meningitis. Patients with active infections requiring systemic intravenous therapy. Mental illness or other illnesses, such as uncontrollable heart disease or pulmonary disease, diabetes, etc. Subjects who are known to be allergic to any of the constituents of the drug being studied. Subjects with a recent history of drug abuse (including alcohol) within one year. Compliance is poor and can not cooperate with clinical research. Female subjects who are pregnant or breastfeeding, or who are expected to be pregnant during the trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm: CIK+PD-1 inhibitor+chemotherapy<br>CIK cell, IBI308, Pemetrexed, Liposome paclitaxel, Carboplatin IBI308 intravenous infusion 200mg d1; Pemetrexed intravenous infusion 500mg/m2 d2 or Liposome paclitaxel intravenous infusion 135mg/m2 d2; Carboplatin intravenous infusion AUC5 d2; CIK cells, 1x10^10 (10 billion ), intravenous infusion,d14; Q3W. | Biological: CIK cell<br>* CIK cell injection<br>* Other names: Autologous cytokine-induced killer cells;Biological: Sintilimab Injection<br>* IBI308 injection<br>* Other names: PD-1 inhibitor;Drug: Pemetrexed<br>* Pemetrexed injection<br>Drug: Liposome paclitaxel<br>* Liposome paclitaxel injection<br>Drug: Carboplatin<br>* Carboplatin injection<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | ORR was calculated by the percentage of patients with a confirmed complete (CR) or partial response (PR). | 2 years |