Clinical study of a novel oncolytic virus Ad-TD-nsIL12 in the treatment of primary high-grade glioma

This study will conduct two prospective, single-arm, single-center, exploratory clinical trials aimed at assessing the preliminary efficacy and safety of the novel oncolytic adenovirus Ad-TD-nsIL12 in treating primary HGG. Trial 1 will preliminarily evaluate the efficacy and safety of Ad-TD-nsIL12 as neoadjuvant treatment for patients with non-functional zone primary HGG; Trial 2 will preliminarily evaluate the efficacy and safety of Ad-TD-nsIL12 in treating patients with functional zone and thalamic primary HGG, as well as their quality of life.

Inclusion Criteria:

1. Age 18-80 years old (including cut-off value), both male and female;
2. Glioma that meets the 2021 edition of the World Health Organization (WHO) classification criteria for central nervous system tumors and has not undergone any anti-tumor treatment;
3. The lesion is located in the non-functional area (Experiment 1) / the lesion is located in the functional area and thalamus (Experiment 2);
4. Have an intracranial measurable target lesion (refer to the iRANO standard);
5. Karnofsky Performance Score (KPS) ≥ 60 points;
6. Expected survival ≥ 3 months;
7. Good organ function;
8. Subjects of childbearing potential and their partners who are sexually active must be willing to use a medically approved effective method of contraception, such as double-barrier contraception, during treatment and within 6 months after the last dose, and men agree not to donate sperm;
9. Subjects of reproductive potential and their partners who are sexually active must be willing to use medically recognized effective contraception methods during treatment and for 6 months after the last dose, such as double-barrier contraception, and male subjects must agree not to donate sperm;
10. Females of reproductive potential must have a negative blood pregnancy test result within 7 days prior to the first dose and be willing to undergo additional pregnancy tests during the study. Reproductive potential refers to women who have not undergone surgical sterilization (i.e., bilateral tubal ligation, bilateral oophorectomy, or total hysterectomy) or are not postmenopausal. Menopause is defined as 12 months of amenorrhea in women over 45 years old, excluding other causes of amenorrhea. Additionally, for women under 50, serum follicle-stimulating hormone (FSH) levels must be in the postmenopausal range to confirm menopause;
11. Good compliance, willing and able to follow all study procedures and cooperate with follow-up observations.

Exclusion Criteria:

1. Received any anti-tumor therapy (referring to the tumor to be observed) in the past;
2. Underwent major organ surgery (excluding needle biopsy) or significant trauma within 4 weeks before the first dose, or required to undergo elective surgery during the study;
3. Known or suspected allergy to the active ingredients, excipients and contrast agents of the study drug;
4. Those with a history of organ transplantation or planned organ transplantation during the study;
5. Those with active infection or uncontrollable infection requiring intravenous systemic treatment, or unexplained fever >38.5°C during screening and before the first dose;
6. Severe coagulation disorders or other obvious evidence of bleeding risk; History of gastrointestinal bleeding; Any other ≥ CTCAE grade 2 bleeding event in the past 6 months;
7. Subjects who have received systemic steroid drugs (> 10 mg/day of prednisone or equivalent) or other immunosuppressive agents within 14 days before the first dose; The following are excluded: treatment with topical, ocular, intraarticular, intranasal, and inhaled corticosteroids; short-term use of corticosteroids for prophylactic treatment (e.g., to prevent contrast allergy);
8. Adverse reactions of previous anti-tumor therapy have not recovered to CTCAE 5.0 grade ≤ grade 1 (except for toxicities judged by the investigator to have no safety risk, such as alopecia, grade 2 peripheral neurotoxicity, etc.);
9. History of immunodeficiency, including positive HIV antibody test;
10. Active hepatitis B (HBsAg positive and HBV-DNA> 500 IU/ml or the lower limit of the test of the study center [only if the lower limit of detection of the study center is higher than 500 IU/ml]); Active hepatitis C (positive for HCV antibody and lower limit of HCV-RNA> detection by the study center), positive Treponema pallidum antibody;
11. Poorly controlled hypertension as judged by the investigator (arterial hypertension that is still uncontrolled under standard treatment: systolic blood pressure ≥160mmHg and/or diastolic blood pressure ≥100mmHg);
12. History of severe cardiovascular disease, such as: ventricular arrhythmia requiring clinical intervention; QTc interval> 480 ms; Acute coronary syndrome, congestive heart failure, stroke, or other grade III or above cardiovascular events within 6 months prior to the first dose; New York Heart Association (NYHA) cardiac function grade ≥ II or left ventricular ejection fraction (LVEF) < 50%;
13. Other uncured malignant tumors within or at the same time within the past 3 years, except for carcinoma in situ that is considered clinically curable, such as cervical cancer in situ and basal cell carcinoma of the skin;
14. Subjects with active or previously suffered autoimmune diseases that may recur (including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), except for clinically stable autoimmune thyroiditis;
15. Those who have received live attenuated vaccines or recombinant vaccines within 4 weeks before the first dose, or inactivated vaccines within 2 weeks before the first dose;
16. Previous immunotherapy with irAE grade evaluation ≥3;
17. Those with two or more intracranial lesions, or extracranial metastasis;
18. Those with neoplastic lesions in the brainstem, cerebellum, posterior fossa or spinal cord, leptomeningeal disease;
19. Diffuse subependymal and subarachnoid disease;
20. Those with a history of encephalitis, multiple sclerosis, and other central nervous system infections;
21. Those with cerebral herniation syndrome;
22. Known alcohol or drug dependence;
23. Mental disorders or poor compliance;
24. Pregnant or lactating females;
25. The investigator believes that the subject has other serious systemic diseases or other reasons that are not suitable for participating in this clinical study.