Clinical trial NCT04919616: An Exploratory Clinical Study of TILs in the Treatment of Recurrent / Refractory Non-small Cell Lung Cancer (NSCLC)
Official title: An Exploratory Clinical Study of Autologous Tumor Infiltrating Lymphocytes (TILs) in the Treatment of Recurrent and Refractory Non-small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: Lymphocytes, Tumor-Infiltrating; TILs
NSCLC
Lead sponsor: Shanghai OriginCell Therapeutics Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-06-09
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is an open, single-arm, dose-escalating phase I exploratory clinical trial to observe the safety, tolerability and preliminary efficacy of different doses of TILs in the treatment of relapsed and refractory NSCLC（Non-small cell lung cancer）.

The study includes 7 stages: ① screening period; ② tissue collection; ③ TILs cell production and preparation; ④ lymphocyte depletion pretreatment; ⑤ TILs cell infusion; ⑥ safety and efficacy evaluation; ⑦ follow-up.


Eligibility criteria: Inclusion Criteria:

1. To participate in clinical trials and sign an informed consent form voluntarily;
2. 18-70 years old;
3. ECOG (Eastern Cooperative Oncology Group) score is 0 or 1;
4. The patient's pre-survival period exceeds 3 months;
5. Patients with advanced stage IIIB or above (according to AJCC 8th Edition lung cancer staging criteria), and patients with stage IIIA or above who received targeted drugs or PD-1 treatment then failed;
6. Patients who have received systemic therapy of anti-tumor therapy (including chemotherapy, radiotherapy, immunotherapy, biotherapy or targeted therapy), and whose progress has been confirmed after treatment;
7. At least one measurable target lesion defined by RECIST v1.1 (Response Evaluation Criteria in Solid Tumours);
8. At least one tumor with a diameter of more than 10 mm and a volume of 1.5 cm3 can be resected or biopsied, and TILs can be separated after resection, or TILs can be separated from malignant effusion;
9. Blood routine test reached the following indicators: lymphocyte count ≥ 0.4 × 109 / L, neutrophils ≥ 1.0 × 109 / L, platelet ≥ 60 × 109 / L, hemoglobin ≥ 60g / L;
10. Liver and kidney function: ALT (alanine aminotransferase) or AST (aspartate aminotransferase) index \< 2.5 times of normal value; Creatinine clearance rate \> 50 ml / min; Total bilirubin \< 1.5 times of normal value; Prothrombin time prolongation ≤ 4 s;
11. No heart disease or coronary heart disease, echocardiogram shows normal diastolic function, left ventricular ejection fraction (LVEF) ≥50%, and no serious arrhythmia;
12. Treatment methods for malignant tumors, including radiotherapy, chemotherapy and biological agents (including granulocyte colony-stimulating factor G-CSF, targeted drug therapy, etc.), must be stopped 14 days before obtaining tumor tissue;
13. Female patients with fertility must have a negative pregnancy test;
14. The fertile person or fertile partner must be willing to use an approved and effective contraceptive method during the treatment period and within 12 months after receiving all treatments related to the treatment regimen.

Exclusion Criteria:

1. Patients with a history of allergy to any component of the study drug;
2. Patients with symptomatic and/or untreated brain metastases;
3. Patients receiving systemic steroid therapy with prednisone or other steroid equivalent ≥ 10 mg / day. Patients with adrenocortical insufficiency receiving prednisone or other steroid equivalent ≤ 10 mg / day may be eligible;
4. Patients who received live or attenuated vaccines within 28 days before the start of treatment;
5. Patients who have received anti-cancer chemotherapy, radiotherapy or other medications within 2 weeks before screening;
6. Patients who participated in another interventional clinical study within 3 weeks before screening;
7. Patients with other primary malignant tumors in the past 3 years;
8. Patients who underwent organ transplantation or cell transplantation in the past 20 years;
9. Active infections requiring systemic treatment;
10. The subjects with positive HBsAg or HBcAb and more than 100 copies / L of HBV DNA in peripheral blood; HCV antibody and HCV RNA in peripheral blood were positive; HIV antibody positive patients; Syphilis antibody was positive in the first screening;
11. Active or previously recorded autoimmune or inflammatory diseases;
12. Patients with any form of primary or acquired immunodeficiency;
13. Patients with inherited or acquired coagulation disorders;
14. Patients with uncontrollable brain metastasis, spinal cord compression, cancerous meningitis within 8 weeks before the first medication, or brain or leptomeningeal disease detected by CT or MRI during screening;
15. Serious mental illness can hinder the full informed consent;
16. Breast feeding female patients;
17. Any investigator decides that it is not appropriate to participate in this trial.

Primary outcomes:
measure: DLT（Dose limiting toxicity）
timeFrame: 28 days
Secondary outcomes:
measure: Objective Response Rate, ORR
timeFrame: 3 Months
measure: Duration of Response, DOR
timeFrame: 2 years
measure: Progression-Free Survival, PFS
timeFrame: 2 years
measure: overall survival, OS
timeFrame: 2 years
measure: Disease Control Rate, DCR
timeFrame: 2 years
Other outcomes:
Locations:
Study officials:
References: