gene therapy for neurofibromatosis type 2 (nf2) with st002

Conditions: NF2 Deficiency

Summary: this is an open-label, single-arm, dose-escalation pilot study to evaluate the safety, tolerability and preliminary efficacy of st002 in the treatment of patients with nf2 mutation-related solid tumors. st002 injection is a gene therapy product designed for nf2. by reinserting the normal xxx gene into genetically deficient tumor cells, the product expresses merlin. this regulates gene transcription in tumor cells, controls the tumor microenvironment, and inhibits tumor growth and invasion, achieving therapeutic effects.

this is an open-label, single-arm, dose-escalation pilot study to evaluate the safety, tolerability and preliminary efficacy of st002 in the treatment of patients with nf2 mutation-related solid tumors. using a 3+3 dose escalation design, three dose groups are formulated, and three to six patients are expected to be enrolled in each dose group. a total of nine to eighteen - patients with nf2 gene mutation related solid tumors will be enrolled.

Eligibility criteria:
inclusion criteria: * age ≥16 years old, gender not limited; * patients must meet the diagnostic criteria for nf2 gene mutations, which are benign or malignant solid tumors with confirmed nf2 gene mutations or no expression of the nf2 protein product merlin in peripheral blood or tumor tissue, and no standard treatment or with standard treatment failure; * at least one measurable and injectable superficial lesion (according to recist or itrecist criteria); * having sufficient organ and bone marrow function: 1. blood routine (no transfusion or treatment with colony-stimulating factor within 14 days): neutrophil count (anc) ≥ 1.5 × 10 9 /l, hemoglobin (hb) ≥ 90g/l, platelet count (plt) ≥ 75 × 10 9 /l; white blood cell count (wbc)\>3.0 × 10 9 /l; 2. liver function: serum total bilirubin (tbil) ≤ 1.5 × uln, alt≤2.5×uln， ast ≤ 2.5 × uln (alt ≤ 5 × uln, ast ≤ 5 × uln in patients with liver metastasis); 3. renal function: serum creatinine (cr) ≤ 1.5 × uln, or creatinine clearance rate (crcl) ≥ 50ml/min; d) coagulation function: prothrombin time (pt) ≤ 1.5 × uln, activated partial thromboplastin time (aptt) ≤ 1.5 × uln, international normalized ratio (inr) ≤ 1.5 × uln; * patients must voluntarily participate in clinical trials, demonstrate adherence to the study protocol, cooperate well with researchers, and sign a written informed consent form. exclusion criteria: * has participated in or is currently participating in other clinical studies nf2 targeting gene therapy; * history of severe neurological disorders such as epilepsy (excluding neurofibromatosis); * patients who are allergic to lentiviral vectors and their excipients; * patients with poorly controlled hypertension (systolic blood pressure\>150 mmhg and/or diastolic blood pressure\>100 mmhg under regular medication control), as well as those with a history of hypertensive crisis or hypertensive brain disease; * suffering from unstable angina or acute myocardial infarction, or having a history of both within the past six months; * patients with a history of malignant tumors within the past 5 years, except for cured basal cell carcinoma, squamous cell carcinoma of the skin, cervical cancer, and gastrointestinal cancer; * during the study period, premenopausal women who are pregnant, breastfeeding, has a positive pregnancy test, or are unwilling to take contraceptive measures.