Overview

A Single-Arm, Open-Label, Interventional Study to Evaluate the Efficacy of HS-IT101 Autologous Tumor-Infiltrating Lymphocyte (TIL) Cell Therapy After Lymphodepleting Preconditioning with Fludarabine and Cyclophosphamide and Subsequent Interleukin-2 Therapy in Patients with Advanced Non-Small Cell Lung Cancer.

Eligibility

Inclusion Criteria:

1. Age 18 to 75 years;
2. Patients with histologically or cytologically confirmed advanced, recurrent, or metastatic non-small cell lung cancer who have failed standard therapy or are intolerant to other standard therapies;
3. At least one tumor lesion that has not received radiotherapy or other local treatment within 28 days and can be surgically resected and/or biopsied for the preparation of autologous tumor-infiltrating lymphocytes;
4. After sampling, at least one measurable lesion as defined by RECIST 1.1 that has not received radiotherapy or other local treatment;
5. ECOG performance status ≤ 1;
6. Adequate organ and bone marrow function as assessed during the screening period;
7. Left ventricular ejection fraction (LVEF) ≥ 50% on echocardiography; no arrhythmia requiring treatment; Fridericia-corrected QT interval (QTcF) ≤ 470 ms; baseline oxygen saturation \> 91% on room air;
8. Prior treatment-related adverse events have recovered to ≤ Grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) 6.0 before tumor sampling;
9. Agree to use effective non-pharmacological contraceptive measures from the time of signing informed consent until 1 year after TIL cell infusion;
10. Fully understand the trial and voluntarily sign the informed consent form, and be able to comply with the visits and related procedures specified in the protocol.

Exclusion Criteria:

1. Patients with a history of severe hypersensitivity reactions to any drug used during the study;
2. Any uncontrolled clinical problem, including but not limited to: poorly controlled hypertension; congestive heart failure;
3. Any of the following events within 6 months prior to screening: deep vein thrombosis or pulmonary embolism; myocardial infarction; severe or unstable arrhythmia or angina pectoris; percutaneous coronary intervention, acute coronary syndrome, or coronary artery bypass grafting; cerebrovascular accident, transient ischemic attack, or cerebral embolism;
4. Active autoimmune disease requiring systemic treatment during the study;
5. History of organ transplantation or hematopoietic stem cell transplantation;
6. Use of any immunosuppressive medications, such as corticosteroids, within 4 weeks prior to tumor tissue collection, or presence of a concurrent disease that, in the investigator's judgment, requires immunosuppressive medication during the study. However, physiological doses of glucocorticoids, intranasal or topical corticosteroids are allowed;
7. Received systemic anticancer therapy within 4 weeks prior to preconditioning, or plan to participate in another interventional clinical trial during the study;
8. Presence of acute or chronic infection, including: HIV positive, positive Treponema pallidum antibody, or clinically active hepatitis B or C; Active infection requiring systemic treatment or active tuberculosis infection;
9. Major organ surgery or significant trauma within 4 weeks prior to screening, or requirement for elective surgery during the study;
10. Surgical complications or delayed wound healing prior to screening that, in the investigator's judgment, would increase the risk of lymphodepleting preconditioning, adoptive TIL therapy, and IL-2 adjuvant therapy;
11. Diagnosis of another primary malignancy within 5 years prior to screening, excluding curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or curatively resected carcinoma in situ;
12. Severe respiratory disease;
13. Gastrointestinal bleeding requiring surgical treatment, intestinal ischemia, or perforation;
14. Known leptomeningeal metastasis; known other central nervous system metastases that are not effectively controlled after treatment or untreated;
15. Previous treatment with a similar cell therapy product;
16. Pregnant or breastfeeding women;
17. Known psychiatric disorders, alcoholism, drug abuse, or substance abuse, and any other condition that the investigator considers unsuitable for participation in this study.