A Study of NBL-020 Injection in Subjects With Advanced Malignant Tumors.

Exclusion Criteria

• •1. Subjects with a history of severe allergies to monoclonal antibodies;
• •2. Active pia mater lesions or uncontrolled brain metastases exist. Subjects with suspected or confirmed brain metastasis can be enrolled as long as they are asymptomatic and do not require treatment (such as radiotherapy, surgery, or corticosteroid therapy) to control the symptoms of brain metastasis. For subjects with brain metastasis requiring treatment, their symptoms remain stable (without hormone maintenance treatment, without symptoms of brain metastasis) for 2 weeks after treatment, and they can be enrolled.
• •3. Subjects with active autoimmune diseases or a history of autoimmune diseases, but with the following diseases are allowed to be included in the study: well controlled type I diabetes, well controlled hypothyroidism only requiring hormone replacement treatment, skin diseases without systemic treatment (such as vitiligo, psoriasis or alopecia), or subjects who are expected to have no relapse under the condition of no external trigger factors;
• •4. Having a history of primary immunodeficiency, a history of allogeneic organ transplantation, or a history of allogeneic hematopoietic stem cell transplantation;
• •5. Chronic hepatitis B (HBsAg and/or HBcAb positive but HBV DNA\<2000 IU/mL can be included), chronic hepatitis C (HCV antibody positive but HCV RNA negative can be included), and HIV antibody positive;
• •6. The toxicity of previous anti-tumor treatments has not returned to ≤ Grade 1 (except for alopecia, pigmentation, or other toxicity that the researchers believe is not a safety risk to the subjects);
• •7. Have a history of serious cardiovascular disease, including but not limited to:
• •1. Serious cardiac rhythm or conduction abnormalities, including but not limited to ventricular arrhythmias requiring clinical intervention, third degree atrioventricular block, within 6 months prior to the first dose of the investigational drug;
• •2. Have a history of myocardial infarction, unstable angina, angioplasty, or coronary artery bypass surgery within 6 months before the first dose of the experimental drug;
• •3. Heart failure, classified as Grade Ш or above by the New York Heart Association (NYHA);
• •4. Subjects with prolonged QT/QTc interval in the screening period electrocardiogram);
• •5. During the screening, echocardiography showed left ventricular ejection fraction (LVEF)\<50%;
• •6. Poor control of hypertension (screening period systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg);
• •8. Uncontrollable serous cavity effusion that requires frequent drainage or medical intervention (such as pleural effusion, abdominal effusion, pericardial effusion, etc., which requires additional intervention within 2 weeks after the intervention, excluding exfoliative cytology testing of the exudate) within 7 days before the first dose of the experimental drug;
• •9. Severe or active infections (including tuberculosis infections) that require systemic antibacterial, antifungal, or antiviral treatment within 14 days before the first use of the experimental drug, except for subjects with viral hepatitis receiving antiviral treatment;
• •10. Received any anti-tumor treatment (including chemotherapy, targeted therapy, immunotherapy, etc.) and any clinical research treatment within 4 weeks or 5 half-lives before the first administration (whichever is shorter);
• •11. Have a history of (non-infectious) pneumonia/interstitial lung disease requiring steroid treatment, or currently have (non-infectious) pneumonia/interstitial lung disease requiring steroid treatment.
• •12. Subjects are required to receive systemic corticosteroids (\>10 mg daily prednisone or equivalent) or immunosuppressive therapy within 14 days before the first dose. Inhalation or local application of corticosteroids, adrenal hormone replacement therapy, and short-term (≤ 7 days) use of corticosteroids to prevent contrast agent allergies are allowed.
• •13. History of immune related adverse events (immune-related AE) ≥ Grade 3 (CTCAE 5.0) after receiving immunotherapy;
• •14. Previously received targeted TNFR2 treatment;
• •15. Those who have undergone major surgery within 4 weeks before the first administration and have not yet fully recovered, or plan to undergo major surgery during the study period;
• •16. Previous malignancies other than the disease under study within 3 years, except for those that can be cured through local treatment, such as skin basal cell carcinoma, cervical or breast cancer in situ;
• •17. Pregnant or lactating women;
• •18. Participate in another clinical study at the same time, unless it is an observational (non-intervention) clinical study or during the follow-up period of an intervention study;
• •19. Has a clear history of neurological or mental disorders, including epilepsy or dementia;
• •20. Other circumstances that researchers believe not suitable to participate in clinical trials, including but not limited to: subjects with severe or uncontrollable medical conditions, safety risks, interference with the interpretation of research results, and impact on trial compliance.