Gene Therapy for Neurofibromatosis Type 2 (NF2) with ST002

Official title

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

Overview

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.

Detailed description

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.

Interventions

• Genetic ST002
  Single multi-point intra-tumoral injection of ST002, a lentiviral vector designed to drive expression of the NF2 protein product, Merlin.

Primary outcome measures

• Safety evaluation [Time frame: From baseline to Week 24 after administration]

Secondary outcome measures (2)

• Efficacy evaluation [Time frame: Day 21 after administration, and at the end of study follow-up, and at early withdrawal. The frequency of checks during the research period can be adjusted according to the researcher's judgement.]
• Efficacy evaluation [Time frame: Day 21 after injection]

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:

• 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;
• 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);
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shuhang Wang — Beijing

Identifiers

NCT: NCT06834438 · ST002-IIT-2024-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗