Treatment for advanced non-small cell lung cancer using modified CAR-T cells

A Single-arm, Open-label, Phase I Study to Evaluate the Safety and Efficacy of CXCR5 Modified EGFR Chimeric Antigen Receptor Autologous T Cells in EGFR-positive Patients With Advanced Non-small Cell Lung Cancer

This study is testing a new type of CAR-T cell treatment for people with advanced non-small cell lung cancer to see if it is safe and works better than standard therapies.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 11 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Second Affiliated Hospital of Guangzhou Medical University (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy, Chimeric Antigen Receptor
• Locations: 1 site (Guangzhou)
• Trial ID: NCT05060796 on ClinicalTrials.gov

What this trial studies

This study involves the intravenous infusion of CXCR5 modified EGFR targeted CAR-T cells in patients with advanced non-small cell lung cancer (NSCLC). It is a single-arm, open-label trial that evaluates the safety and effectiveness of this innovative treatment approach. Participants will undergo detailed monitoring of the dosage and timing of the CAR-T cell infusion, with assessments of adverse events and treatment outcomes compared to previous standard therapies. Blood samples will be collected to analyze the activity and pharmacokinetics of the CAR-T cells over a 12-month period.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with advanced NSCLC who have shown EGFR expression and have experienced treatment failure with standard therapies.

Not a fit: Patients without measurable tumor lesions or those with low EGFR expression may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced NSCLC who have limited treatment alternatives.

How similar studies have performed: While CAR-T cell therapies have shown promise in hematological malignancies, this specific approach for NSCLC is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. All subjects or legal guardians must sign the informed consent form approved by the ethics committee in writing before starting any screening procedure;
2. 18 Years to 75 Years, Histologically or cytologically confirmed Routine treatment of patients with advanced non-small cell lung cancer(Including TKI treatment failure patients);
3. After the signature of the informed consent and prior to the collection of a single nuclear cell, the immuno- histochemical test must determine that the expression of EGFR in the tumor site of the patient reaches the positive standard and the score is 2 + or more;
4. Pathological results suggest that CXCL13 factor positive rate ≥ 10 %;
5. According to RECIST 1.1. The patient has at least one tumor lesion that can be measured (Results available within one month prior to screening period);
6. Expected survival time ≥ 12 weeks;
7. The Eastern oncology group strength status score (ECOG) was 0-1;
8. Patients must have evidence of adequate hepatic and renal function as evidenced by the following laboratory parameters: Serum creatinine≤ 1.6 mg/ml or the creatinine clearance ≥ 40 ml/min/1.73m. Total bilirubin \< 1.5 times upper limits of normal;
9. The hemodynamics determined by echocardiography or multichannel radionuclide angiography(MUGA) are stable and the left ventricular ejection fraction (LVEF)≥50%;
10. Have sufficient bone marrow reserves (subjects can meet this requirement through blood transfusion), defined as: The number of white blood cells should not be less than 2 × 10\^9/L;Platelet≥100 x 10\^9/L; Hemoglobin ≥100 g/L;
11. If the patient uses the following drugs, the following conditions must be met:

    Glucocorticoid: The therapeutic dose of glucocorticoid must be stopped 2 weeks before the EGFR CAR-T infusion. However, the following physiological replacement doses of glucocorticoids are allowed: 12 mg/m2 / dihydrogenated cortisone or equivalent; Immunosuppressive drugs: any immunosuppressive drugs must be stopped before they are selected for 4 weeks; Stop using granulocyte colony factor a week before plasmaphoresis.
12. Women of childbearing age and all male subjects must agree to use effective contraceptive methods for at least 52 weeks after EGFR CAR-T infusion, and until two consecutive PCR tests show that CAR-T cells are no longer present in the body.

Exclusion Criteria:

1. Patients who have previously received any gene therapy product treatment, including CAR-T treatment;
2. Patients with uncontrolled hypertension (\> 160/95), unstable coronary artery disease confirmed by uncontrolled arrhythmias, unstable angina, decompensated congestive heart failure(\>New York Heart Association Class II) or myocardial infarction within 6 months before cell infusion;
3. Patients with severe liver and kidney dysfunction or consciousness disorders;
4. Patients who had undergone antitumor chemotherapy other than lymphocyte clearance chemotherapy within 14 days before the EGFR CAR-T infusion;
5. Screening of patients who had received other research drugs within 30 days before infusion;
6. Patients undergoing radiotherapy and TKI treatment within 2 weeks before infusion ;
7. Patients with active hepatitis B: HBVDNA \>1000 cps/ml;
8. Patients with HIV antibody, hepatitis C antibody, syphilis spirocyte positive；
9. Patients with The sputum smear and tuberculosis infection T cell test positive;
10. Patients with Interstitial lung disease or pneumonia;
11. Patients with acute life-threatening bacteria, viruses or fungal infections that have not yet been controlled(for example, before transfusion ≤ 72 hours of blood culture positive);
12. Patients with central nervous system metastasis (after cerebral metastasis treatment is stable for more than 4 weeks and patients with asymptomatic brain metastasis do not need treatment), pericardial metastasis accompanied by a large amount of pericardial effusion;
13. Patients with a previous or concurrent second tumor, with the following exceptions:

    Adequate treatment of basal or squamous cell carcinoma(adequate wound healing prior to entry into the study);In situ cancer of the cervix or breast cancer with no signs of recurrence at least three years prior to the study following curable treatment; The primary malignant tumor has been completely removed and has been completely relieved for 5 years.
14. Pregnant or lactating women;
15. Patients with history of T cell tumors or present with the disease.
16. Having autoimmune or inflammatory disorders of active nerves (such as Guillian-Barre syndrome, amyotrophic lateral sclerosis);
17. The researchers believe that other circumstances such as compliance should not be involved in this clinical trial.

Where this trial is running

Guangzhou

• Second Affiliated Hospital of Guangzhou Medical University — Guangzhou, China (Recruiting)

Study contacts

• Principal investigator: Zhenfeng Zhang, MD, PHD — Second Affiliated Hospital of Guangzhou Medical University
• Study coordinator: Zhenfeng Zhang, MD, PhD

Conditions Non Small Cell Lung Cancer