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This is a single-arm, open-label, single-dose study consisting of a dose-escalation phase followed by a dose-expansion phase. Four dose levels are planned. Dose escalation will be conducted using an accelerated titration combined with a traditional "3+3" design. A total of 27 to 33 subjects are planned to be enrolled. The primary objective is to evaluate safety, with secondary objectives exploring efficacy and viral shedding. The study duration, from the first subject enrolled to the completion of the last subject's observation period (Day 57 visit), is estimated to be 1 to 2 years. A long-term survival follow-up period of approximately 15 years, or until all subjects are lost to follow-up or deceased, is planned. All data up to Day 57 will be used to support the initiation of a Phase II clinical trial. Any safety and efficacy data will be submitted to regulatory authorities on a rolling basis during the trial.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single intratumoral administration of JL15003 Injection | Experimental | Single intratumoral administration of JL15003 Injection |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| JL15003 Injection | Biological | Single intratumoral administration of JL15003 Injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| The incidence and severity of adverse events (AEs) | From date of randomization until the date of death from any cause, assessed up to 180 months | |
| The occurrence of dose limiting toxicity (DLT) | Within 28 days after the first administration | |
| The Maximum tolerated dose (MTD) | After DLT observation in each dose group and after efficacy evaluation in each dose group,up to 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Objective response rate (ORR) | From date of drug administration until the date of disease progression, or death from any cause, assessed up to 12 months | |
| Viral shedding:Copy number of JL15003 in blood, throat swab, and fecal samples | From the first administration to Week 8. |
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Inclusion Criteria:
Exclusion Criteria:
Patients who are allergic to any component of the investigational drug, contrast agent Maganweixian, or albumin;
Patients with an impending, life-threatening cerebral herniation syndrome;
Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax > 99.5 F/37.5 C);;
Patients with known history of immunodeficiency (e.g., positive HIV antibody test), other acquired or congenital immunodeficiency diseases, or organ transplantation;
Patients with unstable or severe intercurrent medical conditions such as severe heart (New York Heart Association (NYHA) Class 3 or 4) or uncontrolled diabetes mellitus;
Patients with tumor in the brainstem, cerebellum or spinal cord, or leptomeningeal disease;
Patients with diffuse subependymal disease;
Head MRI suggests tumor enhancement with marginal invasion of the ventricular wall or postoperative tumor cavity connecting to the ventricle;
Patients with a previous history of neurological complications due to poliovirus infection;
Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups);;
Patients with prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin;
Patients who have received antitumor therapy (including but not limited to chemotherapy, targeted therapy, immunotherapy, TTFields, or other investigational antitumor drugs) within 4 weeks prior to the first dose of the study drug or within 5 half-lives of the previous drug (whichever is longer), and has not recovered from the toxicities (i.e., to ≤ Grade 1 per CTCAE v5.0, except for alopecia; peripheral neuropathy up to Grade 2 is acceptable);
Patients have received bevacizumab ≤ 6 weeks and could not exclude pseudo relievers caused by anti angiogenic inhibitors;
Patients who have received Chinese medicine or traditional Chinese patent medicines with anti-tumor effect within 2 weeks prior to the administration of the test drug;
Patients who have received radiation therapy within 12 weeks prior to the administration of the investigational drug, excluding those who have undergone radiation therapy for progressive diseases outside the radiation area and cannot rule out pseudoprogression after radiation/chemotherapy;
Patients with known history of agammaglobulinemia;
Patients on greater than 4 mg per day of dexamethasone or equivalent doses of other hormones (inhaled or localized use of hormones, in the absence of active autoimmune disease) within 2 weeks prior to the administration of the investigational drug;
The laboratory tests before biopsy and administration of the test drug meet the following standards:
Patients with positive syphilis antibody, or active hepatitis [For hepatitis B: positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and HBV-DNA copy number above the upper limit of normal; for hepatitis C: positive HCV antibody and HCV RNA copy number above the upper limit of normal];
Subjects who meet any of the following criteria and have a positive laboratory test result (e.g., T-SPOT.TB test, tuberculosis antibody assay, or tuberculin skin test) that, in the investigator's judgment, indicates an active or suspected tuberculosis (TB) infection.
Subjects who have received any vaccination within 4 weeks prior to the administration of the study drug, with the exception of the trivalent inactivated poliovirus vaccine, non-live seasonal influenza vaccines, or inactivated COVID-19 vaccines;
Pregnancy or lactation, and a woman of childbearing potential who has a positive pregnancy test (within 7 days) prior to treatment;
Subjects who are unsuitable for participation in this study at the Investigator's discretion.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Union Hospital, Tongji Medical College, Huazhong University of Science and Technology | Wuhan | Hubei | China | |||
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| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
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| Expression of CD155 | From signing the informed consent form to day 28 |
| Disease control rate (DCR) | Up to 12 months |
| Progression-free survival (PFS) | Up to 15 years |
| Duration of response (DOR) | Up to 15 years |
| Overall survival (OS) | Up to 15 years |
| Beijing Tsinghua Changgung Hospital |
| Beijing |
| China |
| Huashan Hospital, Shanghai Medical College, Fudan University | Shanghai | China |
| D009373 |
| Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |