Study of CXCR5 Modified EGFR Targeted CAR-T Cells for Advanced NSCLC

NCT05060796 | Recruiting Early Phase 1

• 1 other identifier: ZZBGCART-014
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single arm, open-label, intravenous infusion of Anti- Epidermal growth factor receptor (EGFR) Chimeric Antigen Receptor (CAR) T cells modified by C-X-C Chemokine receptor type 5 (CXCR 5) in patients with advanced adult non-small cell lung cancer (NSCLC).

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Safety by Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

  The type, frequency, severity, and duration of adverse events as a result of EGFR CAR T cells infusion will be summarized.

  In CAR-T cells infusion, up to 52 weeks.

Secondary Outcomes (1)

• Objective Response Rate (ORR)

  In CAR-T cells infusion, up to 52 weeks.

Study Arms (1)

EGFR CAR-T

EXPERIMENTAL

Group: 3 dose levels

Biological: CXCR5 modified EGFR Chimeric Antigen Receptor Autologous T cells

Interventions

CXCR5 modified EGFR Chimeric Antigen Receptor Autologous T cells BIOLOGICAL

The first dose group: 0.5 × 10\^6/kg CAR positive T cells; The second dose group: 1.58 × 10\^6/ kg CAR positive T cells; The third dose group: 5 × 10\^6/kg CAR positive T cells. The above dose allows a 20 % error; For subjects with body weight greater than 60 kg, the number of cells can only be calculated according to 60 kg of body weight.

EGFR CAR-T

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects or legal guardians must sign the informed consent form approved by the ethics committee in writing before starting any screening procedure;
• Years to 75 Years, Histologically or cytologically confirmed Routine treatment of patients with advanced non-small cell lung cancer(Including TKI treatment failure patients);
• 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;
• Pathological results suggest that CXCL13 factor positive rate ≥ 10 %;
• 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);
• Expected survival time ≥ 12 weeks;
• The Eastern oncology group strength status score (ECOG) was 0-1;
• 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;
• The hemodynamics determined by echocardiography or multichannel radionuclide angiography(MUGA) are stable and the left ventricular ejection fraction (LVEF)≥50%;
• 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;
• 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.
• 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.

You may not qualify if:

• Patients who have previously received any gene therapy product treatment, including CAR-T treatment;
• 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;
• Patients with severe liver and kidney dysfunction or consciousness disorders;
• Patients who had undergone antitumor chemotherapy other than lymphocyte clearance chemotherapy within 14 days before the EGFR CAR-T infusion;
• Screening of patients who had received other research drugs within 30 days before infusion;
• Patients undergoing radiotherapy and TKI treatment within 2 weeks before infusion ;
• Patients with active hepatitis B: HBVDNA \>1000 cps/ml;
• Patients with HIV antibody, hepatitis C antibody, syphilis spirocyte positive；
• Patients with The sputum smear and tuberculosis infection T cell test positive;
• Patients with Interstitial lung disease or pneumonia;
• 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);
• 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;
• 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.
• Pregnant or lactating women;

Sponsors & Collaborators

• Second Affiliated Hospital of Guangzhou Medical University: lead

Study Sites (1)

Second Affiliated Hospital of Guangzhou Medical University

Guangzhou, 510260, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Zhenfeng Zhang, MD, PHD

  Second Affiliated Hospital of Guangzhou Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhenfeng Zhang, MD, PhD

CONTACT

0086-020-39195966; zhangzhf@gzhmu.edu.cn

Bingjia He, MD

CONTACT

14748877800

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2021
• First Posted: September 29, 2021
• Study Start: September 1, 2019
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): November 1, 2034
• Last Updated: June 25, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)