Non small cell lung cancer
Conditions
Interventions
Experimental group:Reinfusion TIL
Sponsors
The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital)
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1.Voluntarily participate in the study, sign the informed consent, and be willing and able to abide by the study protocol; 2.Aged 18 to 70 years (including 18 and 70, calculated on the date of signing informed consent); 3.Stage IIIB to IV NSCLC that cannot be treated with radical surgery or radiotherapy; 4.Patients with EGFR / ALK / ROS1 and other wild-type driver genes failed in first-line platinum containing chemotherapy (including, but not limited to pemetrexed / docetaxel / paclitaxel / gemcitabine combined with platinum drugs); 5.Must have progressed following at least one line of standard treatment, and must have progressed following second line of standard treatment with PD-1; 6.At least one resectable tumor lesion (preferably superficial lymph node) that has not received radiotherapy or other local treatment, and from which at least 0.5cm^3 mass of tissue can be isolated (single source or multiple lesions can be combined); If there is no resectable lesion, a tumor sample of similar size should be obtained by puncture or bronchoscopy for the preparation of autologous tumor-infiltrating lymphocytes (minimally invasive treatment if possible); 7.At least one measurable lesion that meets the RECIST 1.1 definition and has not received radiotherapy or other local treatment (unless these treatments occurred earlier than 3 months and the lesion shows significant progression); 8.Eastern Oncology Collaboration (ECOG) physical status score 0 or 1; 9.Estimated life expectancy of >= 12 weeks; 10.The function of vital organs should meet the following requirements (no blood components or cell growth factors should be used within 14 days before surgery) (1)Blood routine examination: Absolute neutrophil count (ANC) >= 1.5x10^9/L; Lymphocyte counts(LC)>0.5x10^9/L; Platelet >=100x10^9/L; Hemoglobin (Hb) >= 90g/L; (2)Liver function tests: AST, ALT and alkaline phosphatase =45 mL /min (calculated by Cockcroft-Gault formula), or serum creatinine within the normal range; (4)Coagulation function test: APTT=50%; (6)Pulmonary function examination: FEV1%>=60%; 11.Non-surgically sterilized women of childbearing age are required to consent to use at least one medically approved method of contraception (such as an intrauterine device, birth control pill or condom) during the study period and for one year after the study period; Non-surgically sterilized female reproductive age subjects must be negative for serum HCG within 7 days prior to cell transfusion; 12.Prior to tumor sampling, adverse reactions caused by previous treatment had recovered (CTCAE 5.0 <=1) or were able to meet the test values specified in the protocol (except for grade 2 peripheral neuropathy, alopecia, skin leucoplosis/hormone replacement treatment-controlled hypothyroidism, and type 1 diabetes mellitus with well-controlled insulin); 13.Prior to tumor sampling, radiographic records of disease progression since previous treatment must be available.
Exclusion criteria
Exclusion criteria: 1.Patients with active central nervous system (CNS) metastases (patients with stable BMS and no drug treatment within 2 weeks of clinical judgment, except those without hormone dependence); 2.Patients whose spinal cord compression cannot be relieved by surgery and/or radiotherapy cannot be included in the group (treated patients whose symptoms have been relieved by clinical evidence for >=1 week before surgical sampling can be included); 3.A malignancy outside the target indication within 5 years prior to screening (excluding adequately treated basal cell or squamous cell skin cancer and post-radical breast ductal carcinoma in situ); 4.Patients with uncontrolled tumor-related pain as determined by the investigator. Subjects requiring pain medication must have a stable pain medication regimen at the time they enter the study; Symptomatic sites suitable for palliative radiotherapy should be treated before entering the study; 5.Having interstitial pneumonia or clinically significant active pneumonia at the time of screening, or other respiratory diseases that seriously affect lung function; 6.Any active autoimmune disease, history of autoimmune disease, or disease requiring systemic steroid hormone or immunosuppressive drug therapy (>10 mg/ day of prednisone or equivalent hormone); 7.Cardiovascular disease of significant clinical significance, including but not limited to: (1)Congestive heart failure (NYHA classification > Class 2); (2)Unstable angina; (3)Myocardial infarction occurred in past 3 months; (4)Any supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention; 8.Arterial/venous thrombotic events within 5 months prior to enrollment, such as: cerebrovascular accident, deep vein thrombosis and pulmonary embolism occurring; 9.Patients with active tuberculosis infection within 1 year before enrollment, or with a history of active tuberculosis infection beyond 1 year before but without standard treatment; 10.Active infections requiring treatment with systemic anti-infectives (except for topical antibiotics); or those with unexplained fever > 38.5? occurring during the screening period, except for tumor fever; 11.Patients with a history of immunodeficiency, including HIV seropositivity; 12.Patients with active hepatitis B or C. HBsAg or HBcAb positive patients whose HBV DNA test is lower than the lower limit of the normal value in the study center can participate in the study. Patients with POSITIVE HCV antibodies can participate in this study if their HCV RNA test is lower than the lower limit of the normal value detected at the research center. For carriers to participate in the study, antiviral treatment should be arranged as appropriate, and nucleic acid copy number quantitative testing should be conducted regularly during the study period; 13.Patients with contraindications to IL-2 use, such as refractory or intractable epilepsy or active gastrointestinal bleeding; 14.Use of live attenuated vaccine within 4 weeks prior to surgical sampling, or expected use of live attenuated vaccine during the study period; 15.Patients who have received long half-life anti angiogenic drugs within four weeks prior to enrollment, such as the VEGF bevacizumab; 16.Patients plan to receive other clinical trial drugs during the study period; 17.Patients who have previously received allogeneic bone marrow transplantation or solid organ transplantation; 18.Drugs to be used in the study (including but n
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety and tolerance; | — |
Secondary
| Measure | Time frame |
|---|---|
| objective remission rate;disease control rate;progression free survival;response period;overall survival; | — |
Countries
China
Contacts
Public ContactCao Lejie
The First Affiliated Hospital of University of Science and Technology of China
Outcome results
None listed