Overview

This is a single-arm, open-label, Phase I study to evaluate the safety, tolerability, and antitumor activity of TX103 CAR-T cells in subjects with TX103-positive advanced solid tumors. The study also aims to explore the maximum tolerated dose (MTD) and determine the recommended Phase II dose (RP2D) of TX103 CAR-T cell therapy.

Eligibility

Inclusion Criteria:

• 1\. Voluntary participation: Subjects must voluntarily participate in this clinical trial, fully understand and sign the informed consent form (ICF), and be willing and able to comply with all study procedures.

  2\. Age: Male or female patients aged ≥18 years and \<75 years at the time of signing the ICF.

  3\. Diagnosis: Subjects must have B7-H3/CD276-positive advanced solid tumors confirmed by pathology, who have failed standard therapy or are intolerant to standard treatment.

  • Intraperitoneal infusion cohort: limited to subjects with recurrent or metastatic ovarian cancer, fallopian tube cancer, primary peritoneal cancer, or other advanced solid tumors with peritoneal metastases confined to the peritoneal cavity.
  • Intravenous infusion cohort: subjects with advanced solid tumors regardless of peritoneal metastasis, preferably including head and neck squamous cell carcinoma, esophageal cancer, lung malignancies, triple-negative breast cancer, colorectal cancer, and mesenchymal-derived malignancies.

    4\. B7-H3/CD276 expression: Tumor tissue immunohistochemistry (IHC) results show B7-H3/CD276 positivity ≥20%, defined as the percentage of viable tumor cells with positive membrane expression of B7-H3/CD276 in non-necrotic tumor tissue.

    5\. Measurable/evaluable disease:

  • Intraperitoneal infusion cohort, Phase Ia: at least one evaluable lesion per RECIST 1.1;
  • Intravenous infusion cohorts (Ia and Ib) and intraperitoneal infusion cohort (Ib): at least one measurable lesion per RECIST 1.1.

    6\. Performance status: Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

    7\. Life expectancy: Expected survival of \>6 months. 8. Apheresis capability: Adequate venous access for leukapheresis and no contraindications to the procedure.

    9\. Adequate organ function (per NCI CTCAE v5.0) within screening period:

    1. Hematologic: WBC ≥ 3.0×10⁹/L; hemoglobin ≥ 8.0 g/dL; absolute neutrophil count ≥ 1.5×10⁹/L; platelet count ≥ 75.0×10⁹/L. No transfusions or supportive treatments (e.g., G-CSF, erythropoietin, TPO agonists, IL-11) within 14 days before testing.
    2. Renal: Serum creatinine ≤ 1.5× upper limit of normal (ULN) and estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl, per Cockcroft-Gault formula) \> 50 mL/min.
    3. Hepatic: ALT and AST ≤ 2.5× ULN (≤ 5.0× ULN for patients with liver metastases).
    4. Bilirubin: Total bilirubin ≤ 2.0× ULN (except for patients with Gilbert's syndrome).
    5. Coagulation: PT, APTT, or INR ≤ 1.5× ULN (without anticoagulant therapy).
    6. Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50% within 1 month before enrollment.
    7. Pregnancy test: Negative serum pregnancy test for women of childbearing potential.
    8. Contraception: Subjects with reproductive potential must agree to use effective contraception from the date of informed consent signing until 365 days after the last infusion.

       Exclusion Criteria:

• 1\. Pregnant or lactating women. 2. Viral infections:
  1. Positive for HIV antibody or syphilis serologic test;
  2. Positive for HBsAg or HBcAb with HBV DNA ≥ 2000 IU/mL;
  3. Positive for HCV antibody with detectable HCV RNA;
  4. 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.

     4\. 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.

       5\. Receiving systemic immunosuppressive therapy, or judged by the investigator to require long-term immunosuppressants during the study. Topical, inhaled, or intranasal corticosteroids are permitted.

       6\. Prior exposure to any gene-engineered T-cell therapy (including CAR-T or TCR-T) or any other gene therapy.

       7\. 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.

       9\. Imaging (CT/MRI) showing tumor invasion of major blood vessels (e.g., aorta, pulmonary arteries/veins, vena cava) or indistinct vascular margins.

       10\. History of epilepsy or seizure-provoking disorders within 1 year prior to infusion.

       11\. 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).

       12\. 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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1. Active infection requiring systemic therapy prior to lymphodepletion;
2. Uncontrolled cardiac disease: unstable angina, myocardial infarction within 1 year, heart failure (NYHA class ≥ II), or clinically significant arrhythmia requiring treatment/intervention;
3. Poorly controlled hypertension (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg despite therapy);
4. Clinically significant bleeding (e.g., GI bleeding, bleeding ulcers, stool occult blood ++ or above, vasculitis) within 3 months before first infusion;
5. Arterial/venous thrombotic events (e.g., stroke, TIA, intracerebral hemorrhage, DVT, pulmonary embolism) within 6 months before first infusion;
6. Clinically significant pleural, pericardial, or peritoneal effusions not controllable by drainage or other means;
7. Severe cirrhosis, hepatic atrophy, or severe portal hypertension;
8. 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).