Overview

In the first phase, it mainly explores the safety, tolerability and preliminary effectiveness of two doses of OH2 injection in the treatment of patients with recurrent central nervous system tumors; to evaluate the biodistribution and virus shedding of OH2 injection administered in the tumor cavity; to evaluate the level of anti-HSV2 antibody in patients when OH2 injection is administered intracavitary to tumor; to determine the phase II recommended dose (RP2D) of OH2 injection in the treatment of recurrent glioblastoma.

Phase IIa, to evaluate the preliminary efficacy of OH2 injection in the treatment of patients with recurrent glioblastoma after surgery, and to further evaluate the safety of OH2 in the treatment of relapsed glioblastoma.

Eligibility

Inclusion Criteria:

1. Age ≥ 18 years old, male or female;
2. Phase I trials select pathologically confirmed recurrent central nervous system tumors (including but not limited to anaplastic astrocytoma, anaplastic oligoastrocytoma, glioblastoma, gliosarcoma, anaplastic ependymoma, Medulloblastoma, malignant meningioma, melanoma, etc.) postoperative patients; Phase IIa trial selects postoperative patients with pathologically confirmed recurrent glioblastoma
3. KPS score ≥60;
4. Partial or complete tumor resection, Ommaya reservoir has been placed in the operation area, and drug administration conditions are available;
5. As assessed by the investigator, the site of injection of the trial drug is expected to be in the supratentorial area;
6. Life expectancy ≥3 months;
7. Blood routine: WBC≥ 3.0×10^9/L, ANC≥1.5×10^9/L, PLT≥100×10^9/L, Hb≥9.0 g/dL;
8. Liver and kidney function: total bilirubin ≤ 1.5 times the upper limit of the normal value; AST and ALT < 2.5 times the upper limit of the normal value; serum creatinine ≤1.5 times the upper limit of the normal value, or creatinine clearance ≥50 ml/min (calculated by Cockcroft/Gault formula);
9. Coagulation function: INR≤1.5 times the upper limit of the normal value, APTT≤1.5 times the upper limit of the normal value;
10. Women of childbearing age had a negative pregnancy test result within 14 days before enrollment. Female subjects and their spouses received effective contraceptives during and within 6 months of treatment;
11. The subjects voluntarily participated in this study, signed the informed consent form, had good compliance, and cooperated with the follow-up.

Exclusion Criteria:

1.28 days before enrollment, subjects participated in other clinical trial projects.

        2.The subject has received tumor chemotherapy, targeted therapy or immunotherapy within 28
        days before the first use of the test drug.
        3.The subjects have received traditional Chinese medicine, modern Chinese medicine
        preparations and antiviral drugs within 7 days before using the test drug for the first
        time.
        4.Subjects had received radiotherapy to the brain 3 months before their first use of the
        test drug.
        5.Subjects with other active extracranial malignancies requiring concomitant therapy.
        6.Subjects known to be allergic to the test drug or its active ingredients, excipients, and
        imaging contrast agents.
        7.Subjects who are going to undergo or have received tissue/organ transplantation in the
        past.
        8.The subject has active infection or unexplained fever >38.5℃ during the screening period
        and before the first dose.
        9.Subjects with active pulmonary tuberculosis (TB) who are receiving anti-tuberculosis
        treatment or who have received anti-tuberculosis treatment within 1 year before screening.
        10.Anti-HIV(+) or anti-HCV(+) or specific antibody (TPHA) positive or active hepatitis B
        (hepatitis B subjects who meet the following criteria are also eligible for inclusion: a)
        HBV viral load before the first dose The amount must be less than 1000 copies/ml (200
        IU/ml), and subjects should receive anti-HBV treatment throughout the trial drug treatment
        period to avoid viral reactivation; b) For anti-HBc (+), HBsAg (-), anti-HBs ( -) and viral
        load (-) subjects, do not require prophylactic anti-HBV therapy, but require close
        monitoring for viral reactivation.
        11.Cardiovascular disease meets any of the following: a. Congestive heart failure with
        cardiac function ≥ NYHA class III; b. Serious arrhythmia requiring drug treatment; c. Acute
        myocardial infarction, severe or unstable angina pectoris, coronary or peripheral artery
        bypass, or stenting occurred within 6 months before the first administration; d. Left
        ventricular ejection fraction (EF) < 60%; e. QTcF interval > 450 ms in men, > 470 ms in
        women, or risk factors for torsades de pointes such as clinically significant hypokalemia,
        family history of long QT syndrome, or family history as judged by the investigator History
        of arrhythmias (eg, pre-excitation syndrome); f. Uncontrolled hypertension (defined as
        systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg after
        standardized antihypertensive drug treatment).
        12.Subjects with active autoimmune disease or a history of autoimmune disease but may
        relapse, but subjects with the following diseases are not excluded and can be further
        screened: a. Type 1 diabetes; b. Hypothyroidism (if controllable with hormone replacement
        therapy alone); c. controlled celiac disease; d. Skin diseases that do not require systemic
        treatment (eg vitiligo, psoriasis, alopecia); e. Any other disease that will not recur in
        the absence of external triggers.
        13.Subjects with unstable mental illness, alcohol, drug or substance abuse. 14. Female
        subjects who are pregnant or breastfeeding, or who are expected to become pregnant during
        the trial period (from the screening visit until 180 days after dosing) and male subjects
        who are expected to conceive their partner.
        15. The adverse reactions of previous anti-tumor therapy have not recovered to (CTCAE 5.0)
        grade 1 (except for alopecia).
        16. The investigator determines that he has a serious uncontrollable disease, or there are
        other conditions that may affect the acceptance of the treatment in this study, and are
        considered unsuitable to participate in this researcher.
        17. Other investigators deem it unsuitable for enrollment.