Gene Therapy for Neurofibromatosis Type 2 (NF2) with ST002

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: NF2 Deficiency
• Intervention / Treatment: Genetic: ST002

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.

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shuhang Wang, PhD; Phone Number: 13581809307; Email: wangshuhang@cicams.ac.cn
• Study Contact Backup: Name: Ning Li, M.D.; Phone Number: +86 01087788919; Email: lining@cicas.ac.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Shuhang Wang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ST002; Subjects will receive with a single multi-point intra-tumoral injection of ST002 from 1x10^7 to 1x10^8 TU into the tumor.	Genetic: ST002; Single multi-point intra-tumoral injection of ST002, a lentiviral vector designed to drive expression of the NF2 protein product, Merlin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety evaluation	Evaluate the incidence of drug-related adverse events (AEs) and adverse events (SAEs) from baseline to Week 24 after administration, with a focus on neurotoxicity and genome-wide integration carcinogenic risks.	From baseline to Week 24 after administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy evaluation	Evaluate the objective response rate (ORR) (tumor volume reduction) and duration of response (DOR) according to RECIST and itRECIST	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	Percentage of necrosis of tumor cells in the tumor tissue at the injection site, estimated by pathological HE staining, at Day 21 after administration.	Day 21 after injection

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Investigators: Study Director: Shuhang Wang, PhD, National Cancer Center of China

Study record dates

Study Major Dates

• Study Start (Estimated): February 15, 2025
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: February 7, 2025
• First Submitted That Met QC Criteria: February 13, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 13, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: ST002-IIT-2024-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No