Phase I Study of TX103 CAR-T Cells in Participants With Advanced Solid Tumors

Exclusion Criteria25

• \. Pregnant or lactating women. 2. Viral infections:
• Positive for HIV antibody or syphilis serologic test;
• Positive for HBsAg or HBcAb with HBV DNA ≥ 2000 IU/mL;
• Positive for HCV antibody with detectable HCV RNA;
• Presence of other active viremia. 3. Known hypersensitivity, allergy, intolerance, or contraindication to TX103 CAR-T or any component of the study drugs (including fludarabine, cyclophosphamide, or tocilizumab), or history of severe allergic reactions.
• \. Active autoimmune diseases, including but not limited to autoimmune hepatitis, interstitial pneumonitis, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, or hypothyroidism.
• Subjects with vitiligo or childhood asthma that has resolved and requires no intervention may be included.
• Subjects requiring medical intervention for asthma (e.g., bronchodilators) are excluded.
• \. Receiving systemic immunosuppressive therapy, or judged by the investigator to require long-term immunosuppressants during the study. Topical, inhaled, or intranasal corticosteroids are permitted.
• \. Prior exposure to any gene-engineered T-cell therapy (including CAR-T or TCR-T) or any other gene therapy.
• \. History of organ transplantation. 8. Untreated or symptomatic central nervous system (CNS) metastases or leptomeningeal metastases.
• Subjects previously treated for brain/leptomeningeal metastases may be eligible if neurologically stable for ≥1 month (MRI) and off systemic corticosteroids for >2 weeks.
• \. Imaging (CT/MRI) showing tumor invasion of major blood vessels (e.g., aorta, pulmonary arteries/veins, vena cava) or indistinct vascular margins.
• \. History of epilepsy or seizure-provoking disorders within 1 year prior to infusion.
• \. Unresolved toxicities from prior anticancer therapy not recovered to CTCAE v5.0 Grade ≤1, except for investigator-judged non-safety-risk toxicities (e.g., alopecia, Grade 2 peripheral neuropathy, stable hypothyroidism with replacement therapy).
• \. Major surgery or significant trauma within 1 month prior to leukapheresis. 13. Any severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that may increase risk or interfere with study results, including but not limited to:
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• Active infection requiring systemic therapy prior to lymphodepletion;
• Uncontrolled cardiac disease: unstable angina, myocardial infarction within 1 year, heart failure (NYHA class ≥ II), or clinically significant arrhythmia requiring treatment/intervention;
• Poorly controlled hypertension (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg despite therapy);
• Clinically significant bleeding (e.g., GI bleeding, bleeding ulcers, stool occult blood ++ or above, vasculitis) within 3 months before first infusion;
• Arterial/venous thrombotic events (e.g., stroke, TIA, intracerebral hemorrhage, DVT, pulmonary embolism) within 6 months before first infusion;
• Clinically significant pleural, pericardial, or peritoneal effusions not controllable by drainage or other means;
• Severe cirrhosis, hepatic atrophy, or severe portal hypertension;
• Complete intestinal obstruction. 14. History of or concurrent malignancy within the past 3 years, except for adequately treated non-melanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, or breast).