CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

1. Age 18-79, male and female;
2. Predicted survival ≥12 weeks;
3. ECOG score 0-1;
4. Diagnosed with Stage IIIB-IV non-small cell lung cancer (NSCLC) through imaging, histological, and/or cytological examinations
5. For patients with negative driver genes (EGFR/ALK/ROS-1/BRAF V600E/MET exon 14 mutation/NTRK), failed first-line PD-1/PD-L1 immunotherapy combined with platinum-based doublet chemotherapy; For patients with EGFR-sensitive mutations (19del, 21L858R, 18exonG719X, 20exonS768I, 21exonL861Q), they must meet one of the following requirements: a) Failed treatment with 1st or 2nd generation EGFR-TKI, and histologically confirmed T790M mutation negative after treatment failure; b) Failed treatment with 3rd generation EGFR-TKI regardless of T790M mutation status; For patients with other driver genes positive besides EGFR mutation and have approved first-line targeted therapies, failed first-line targeted therapy;
6. Have at least one measurable tumor lesion according to RECIST 1.1;
7. The tumor tissue sample (previous or fresh) shows at least 50% weak positive expression of Trop2 protein;
8. Have adequate organ and bone marrow function, defined as follows:

   Blood routine: Absolute neutrophil count (ANC) ≥ 1.5×109/L, platelet (PLT) ≥ 100×109/L, hemoglobin (Hb) ≥ 90g/L; Liver function: Bilirubin \< 1.5 times the upper limit of normal (ULN), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) \< 2.5 times ULN (in case of liver metastasis, ALP, AST, and ALT \< 5 times ULN are allowed); Renal function: Creatinine clearance rate (CCR) ≥ 60 mL/min (using the standard Cockcroft-Gault formula);
9. For women: surgically sterilized, postmenopausal patients, or those who agree to use a medically accepted contraceptive method (such as intrauterine device, contraceptive pills, or condoms) during and for 6 months after the study treatment period; serum or urine pregnancy test must be negative within 7 days before study enrollment, and must be non-lactating; For men: surgically sterilized or those who agree to use a medically accepted contraceptive method during and for 6 months after the study treatment period.

Exclusion Criteria:

1. Severe infection;
2. Clinically active brain or meningeal metastasis, defined as untreated and symptomatic, or requiring steroids or anticonvulsant therapy to control related symptoms. For asymptomatic brain metastasis subjects, if they have been stable for at least 4 weeks in imaging and neurologically after receiving targeted therapy for brain metastasis, and are on a stable or reduced dose of steroids equivalent to ≤10 mg/day of prednisone, they may be included in the study;
3. Organic heart disease, cardiac insufficiency, heart block above grade II, myocardial infarction within 6 months;
4. Active autoimmune disease;
5. Interstitial lung disease;
6. Active hepatitis B (Hepatitis B surface antigen (HBsAg) positive, HBV-DNA testing required; HBV-DNA ≥500 IU/mL or higher than the lower limit of detection, whichever is higher) or hepatitis C (Hepatitis C antibody positive and HCV-RNA higher than the lower limit of detection);
7. Positive human immunodeficiency virus (HIV) test or history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection;
8. Pregnancy or lactation;
9. Patients with a tendency to bleed, including acute gastrointestinal bleeding, nasal bleeding, hemoptysis, as well as persistent bleeding disorders or coagulation disorders;
10. Patients who have used anti-tumor drugs other than immunotherapy within 3 weeks;

12\. Multiple primary malignancies within 3 years prior to enrollment, except for fully resected non-melanoma skin cancer (e.g., resected basal or squamous cell skin cancer), radically treated carcinoma in situ (e.g., cervical or breast carcinoma in situ), other radically treated solid tumors (e.g., superficial bladder cancer), or contralateral breast cancer; 13. History of allergy to any component of the study drug; 14. Other situations that the investigator deems unsuitable for participation in the study, or other situations that may affect the analysis of the clinical study results.

主要终点：Safety by Common Terminology Criteria for Adverse Events (CTCAE) V5.0 · The type, frequency, severity, and duration of adverse events as a result of Trop2 CAR-NK cells infusion will be summarized. · Up to 1 year；Objective Response Rate (ORR) · Per Response Evaluation Criteria in Solid Tumours (RECIST 1.1) assessed by MRI or CT. ORR defined as the proportion of patients in whom a complete response (CR) or partial response (PR) is observed as best overall response, prior to progression or further anti-cancer therapy. · up to 1 year.
次要终点：Disease control rate (DCR)；Overall survival (OS)

• Anti-Trop2 CAR-NK cell therapy group · EXPERIMENTAL · chemotherapy followed by Trop2 CAR-NK infusion

It is a single-center, open-labeled, single-arm, non-randomized investigator-initiated trial evaluating the efficacy and safety of anti-Trop2 U-CAR-NK Cells Therapy combined with Chemotherapy for Relapsed/Refractory Non-Small Cell Lung Cancer (NSCLC).