NF2
Conditions
Interventions
Group 1:AYK103 + Sindillizumab injection
Group 2:IMM2510
Group 3:SW-NF-001
Sponsors
Shanghai Sixth People's Hospital
Eligibility
Sex/Gender
All
Age
12 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1)>12 years old, male or female; 2)ECOG score 0-1; 3) Clinically or genetically diagnosed patients with NF2; 4) Patients with single/multiple neurofibromatosis that is difficult to treat surgically, or patients with postoperative recurrence; 5) Have at least one measurable lesion according to the solid tumor response evaluation criteria (RECIST1.1); 6) Expected survival =3 months; 7) The main organ function and bone marrow function are normal, meeting the following requirements: a. Hemoglobin =90 g/L; (No transfusion within 14 days) b. Absolute neutrophil count =1.5×109/L; c. Platelet count =90×109/L; d. Total bilirubin =1.5 times upper limit of normal (ULN) e. alanine aminotransferase (ALT) and aspartate aminotransferase (AST)=2.5 times ULN; If there is liver metastasis, ALT and AST are less than 5 times ULN. f. Creatinine =1.5 times ULN; g. left ventricular ejection fraction (LVEF) =50%; QTc Male < 450ms, female < 470ms; 8) International Normalized ratio of prothrombin time (INR) =1.5, partial thromboplastin time (APTT) =1.5 times ULN for patients who did not receive anticoagulant therapy. Patients receiving full or parenteral anticoagulant therapy as long as the anticoagulant dose is stable for at least 2 weeks prior to entering the clinical study and the results of the clotting test are within the limits of local treatment; 9) Women of childbearing age must undergo a negative pregnancy test (serum or urine) within 14 days prior to enrollment and voluntarily use an appropriate method of contraception during the observation period and within 3 months after the last administration of the study drug; For males, surgical sterilization or agreement to use appropriate methods of contraception during observation and within 3 months after the last administration of study medication; 10) Recovery from previous treatment: According to NCI-CTC AE 5.0, the toxicity of previous treatment has been restored to = 1 level (if surgery is performed, the wound has fully healed); 11) The patient voluntarily participates and signs an informed consent form (or signed by their legal representative), with good expected compliance and the ability to cooperate with the study according to the protocol requirements.
Exclusion criteria
Exclusion criteria: 1) Have previously received VEGF antibodies such as bevacizumab treatment or anti-angiogenesis small molecule TKI drugs (such as pezopanib, anrotinib), or have used anti-PD-1 / PD-L1 antibodies, anti-CTLA-4 antibodies and other immunosuppressants. 2) Received the following treatments or medications before the first study treatment: a. Major surgery within 28 days prior to initial study therapy (tissue biopsy required for diagnosis is permitted); b. Receive live attenuated vaccine within 28 days before the first study drug treatment or during the study period and within 60 days after the end of study drug treatment; c. Received any form of antitumor therapy, including radiotherapy, chemotherapy, molecular-targeted therapy and immunotherapy, or participated in another interventional clinical trial within 4 weeks prior to the first investigational drug treatment; For patients receiving antineoplastic drugs, no more than 4 weeks from the last dose or 5 half-lives of the drug; 3) There is a third space effusion with clinical symptoms that cannot be controlled by drainage or other methods (such as a large amount of pleural fluid or ascites); 4) Poor control of hypertension even after medication (persistent increase in systolic blood pressure =150 MMHG or diastolic blood pressure =100 MMHG) 5) uncontrolled cardiac clinical symptoms or conditions, such as (1) NYHA II and above heart failure; (2) Unstable angina pectoris; (3) Myocardial infarction occurred within 1 year; (4) Patients with clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention; 6) Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), untreated active hepatitis (hepatitis B, defined as a positive HBV surface antigen [HBsAg] test result, HBV-DNA = 500 IU/ml, and abnormal liver function; Hepatitis C, defined as hepatitis C antibody [HCV-Ab] positive, HCV-RNA above the lower detection limit of analytical methods, and abnormal liver function) or co-infection with hepatitis B and hepatitis C; 7) Have any active autoimmune disease or history of autoimmune disease (such as interstitial pneumonia, uveitis, enteritis, hepatitis, pituitaritis, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism (may be included after hormone replacement therapy); Patients with complete remission of childhood asthma without any intervention or vitiligo in adulthood could be included, but patients requiring medical intervention with bronchodilators could not be included; 8) Severe infection within 2 weeks prior to the first dose (e.g., intravenous antibiotic, antifungal, or antiviral medication is required), or unexplained fever during the screening period/prior to the first dose > 38.5°C; 9) Arteriovenous thrombosis events occurring within 6 months before enrollment, such as cerebrovascular accidents (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism; 10) Have had or been accompanied by other systemic malignancies within the last 5 years (except cured basal cell carcinoma of the skin, cervical carcinoma in situ and ovarian cancer); 11) Known allergy to any investigational drug or its excipients; 12) Pregnant, lactating patients, patients with reproductive capacity are unwilling to take effective contraceptive measures; 13) A clear history of neurological or psychiatric disorders, including epilepsy and dementia; 14) Known uncontrolle
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| security;6 months mPFSR; | — |
Secondary
| Measure | Time frame |
|---|---|
| objective remission rate;progression free survival;clinical benefit Rate;duration of response; | — |
Countries
China
Contacts
Public ContactShankai Yin
Shanghai Sixth People's Hospital
Outcome results
None listed