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

Inclusion Criteria:

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

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

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

• Intraperitoneal infusion cohort: limited to subjects with recurrent ormetastatic ovarian cancer, fallopian tube cancer, primary peritoneal cancer, orother advanced solid tumors with peritoneal metastases confined to theperitoneal cavity.

• Intravenous infusion cohort: subjects with advanced solid tumors regardless ofperitoneal metastasis, preferably including head and neck squamous cellcarcinoma, esophageal cancer, lung malignancies, triple-negative breast cancer,colorectal cancer, and mesenchymal-derived malignancies.

4. B7-H3/CD276 expression: Tumor tissue immunohistochemistry (IHC) results showB7-H3/CD276 positivity ≥20%, defined as the percentage of viable tumor cellswith 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 perRECIST 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) performancestatus of 0-1.
7. Life expectancy: Expected survival of >6 months. 8. Apheresis capability:Adequate venous access for leukapheresis and no contraindications to theprocedure.
8. Adequate organ function (per NCI CTCAE v5.0) within screening period:
9. Hematologic: WBC ≥ 3.0×10⁹/L; hemoglobin ≥ 8.0 g/dL; absolute neutrophilcount ≥ 1.5×10⁹/L; platelet count ≥ 75.0×10⁹/L. No transfusions orsupportive treatments (e.g., G-CSF, erythropoietin, TPO agonists, IL-11)within 14 days before testing.
10. Renal: Serum creatinine ≤ 1.5× upper limit of normal (ULN) and estimatedglomerular filtration rate (eGFR) or creatinine clearance (CrCl, perCockcroft-Gault formula) > 50 mL/min.
11. Hepatic: ALT and AST ≤ 2.5× ULN (≤ 5.0× ULN for patients with livermetastases).
12. Bilirubin: Total bilirubin ≤ 2.0× ULN (except for patients with Gilbert'ssyndrome).
13. Coagulation: PT, APTT, or INR ≤ 1.5× ULN (without anticoagulant therapy).
14. Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50% within 1month before enrollment.
15. Pregnancy test: Negative serum pregnancy test for women of childbearingpotential.
16. Contraception: Subjects with reproductive potential must agree to useeffective 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 studydrugs (including fludarabine, cyclophosphamide, or tocilizumab), or history ofsevere allergic reactions.

5. Active autoimmune diseases, including but not limited to autoimmunehepatitis, interstitial pneumonitis, uveitis, enteritis, hepatitis,hypophysitis, vasculitis, nephritis, hyperthyroidism, or hypothyroidism.

• Subjects with vitiligo or childhood asthma that has resolved and requiresno intervention may be included.
• Subjects requiring medical intervention for asthma (e.g., bronchodilators)are excluded.

5. Receiving systemic immunosuppressive therapy, or judged by theinvestigator 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-Tor TCR-T) or any other gene therapy.
7. History of organ transplantation. 8. Untreated or symptomatic centralnervous system (CNS) metastases or leptomeningeal metastases.

• Subjects previously treated for brain/leptomeningeal metastases may beeligible if neurologically stable for ≥1 month (MRI) and off systemiccorticosteroids for >2 weeks.

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

10. History of epilepsy or seizure-provoking disorders within 1 year priorto infusion.

11. Unresolved toxicities from prior anticancer therapy not recovered toCTCAE v5.0 Grade ≤1, except for investigator-judged non-safety-risktoxicities (e.g., alopecia, Grade 2 peripheral neuropathy, stablehypothyroidism with replacement therapy).

12. Major surgery or significant trauma within 1 month prior toleukapheresis. 13. Any severe, acute, or chronic medical or psychiatriccondition, or laboratory abnormality that may increase risk or interferewith study results, including but not limited to:

13. Active infection requiring systemic therapy prior to lymphodepletion;

14. Uncontrolled cardiac disease: unstable angina, myocardial infarction within 1year, heart failure (NYHA class ≥ II), or clinically significant arrhythmiarequiring treatment/intervention;

15. Poorly controlled hypertension (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg despitetherapy);

16. Clinically significant bleeding (e.g., GI bleeding, bleeding ulcers, stooloccult blood ++ or above, vasculitis) within 3 months before first infusion;

17. Arterial/venous thrombotic events (e.g., stroke, TIA, intracerebral hemorrhage,DVT, pulmonary embolism) within 6 months before first infusion;

18. Clinically significant pleural, pericardial, or peritoneal effusions notcontrollable by drainage or other means;

19. Severe cirrhosis, hepatic atrophy, or severe portal hypertension;

20. Complete intestinal obstruction. 14. History of or concurrent malignancy withinthe past 3 years, except for adequately treated non-melanoma skin cancer orcarcinoma in situ (e.g., cervix, bladder, or breast).