Clinical Safety and Preliminary Efficacy of MAGE-A4 TCR Gene-Modified T Cells to Treat Malignant Tumors

Phase 1 Study of MAGE-A4 TCR Gene-Modified T Cells to Treat Malignant Tumors

The purpose of this study is to evaluate the clinical safety and preliminary efficacy of MAGE-A4 TCR Gene-Modified T lymphocytes in the treatment of malignant solid tumor patients, such as malignant melanoma and lung cancer.

Inclusion Criteria:

• Sex: male or female
• Age: from 18 to 80 years
• Patients must have histologically confirmed solid tumors that have failed standard therapies (surgery, chemotherapy, radiotherapy) and for which no curative options exist, including, but not limited to:

Non-Small Cell Lung Carcinoma Malignant melanoma Esophageal carcinoma Head and neck carcinoma

• HLA-A*24:02
• MAGE-A4 positive in the test by RT-PCR on tumor tissue or immunohistochemistry of resected tissue of the patient.
• PS ECOG 0 or <2
• Laboratory tests results 7 days before the start of treatment:

White blood cells: more than 3.0 × 109/L Platelets: more than 100 × 109/L Neutrophils: more than 1.5 × 109/L Hemoglobin: more than 80g/L Serum glutamate pyruvate transaminase: less than 2.5 folds of the upper normal limit (ULN) Serum glutamic-oxal (o) acetic transaminase: less than 2.5 × ULN Serum bilirubin: less than 1.25 × ULN Serum creatinine: less than 1.25 × ULN

• Pregnancy test: the test of women of child-bearing period must be negative 7 days before the start of treatment
• Contraception: male and female subjects of child-bearing period must adopt a reliable method of contraception before entry into this study until 30 days after stopping this study
• Informed consent: subject must have the ability to understand and voluntarily sign a written informed consent

Exclusion Criteria:

• Patients with life-threatening condition or complication other than their basic disease
• Pregnant or lactation. Patients both males and female with reproductive potential (i.e. menopausal for less than 1 year and not surgically sterilized) must practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration
• Active systemic infections
• History of neoplasms: other neoplasms
• Medical history: active CNS disease, or congestive heart failure, or severe coronary artery disease, or cardiac arrhythmias, or concomitant corticosteroid therapy
• Metastasis: clinical symptoms of brain metastasis
• Other clinical trial: the subject received other clinical trial before this study
• Laboratory tests: the serum test of human immunodeficiency virus, or hepatitis B virus, or hepatitis C virus was positive
• Compliance: poor compliance