Evaluation of TQ-B3234 Capsules in Patients With Symptomatic, Non-Surgical Type 1 Neurofibromatosis-Associated Plexiform Neurofibromas

Randomized, Double-Blind, Parallel-Controlled, Multicenter Phase III Clinical Trial Evaluating the Efficacy and Safety of TQ-B3234 Capsules Versus Placebo in Patients With Symptomatic, Non-Surgical Type 1 Neurofibromatosis-Associated Plexiform Neurofibromas

This study aims to demonstrate that in subjects with symptomatic, inoperable plexiform neurofibromas associated with neurofibromatosis type 1, TQ-B3234 capsules significantly improve the objective response rate at Week 24 compared to placebo.

Inclusion Criteria:

• The subject voluntarily joins this study, signs the informed consent form, and demonstrates good compliance.
• Age ≥18 years (calculated from the date of signing the informed consent form).
• Diagnosis of symptomatic, non-resectable neurofibromatosis type 1 (NF1)-associated plexiform neurofibroma (PN) requiring systemic therapy per investigator judgment.
• At least one measurable lesion with a dimension ≥3 cm.
• There should be no significant changes in the use of chronic neuropathic pain medications within 28 days prior to study enrollment.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Laboratory tests meet the protocol criteria.
• Women of childbearing potential must agree to use effective contraception during the study and for 6 months after study completion. A negative serum pregnancy test must be documented within 7 days prior to study enrollment. Men must agree to use effective contraception during the study and for 6 months after study completion.

Exclusion Criteria:

• Confirmed or suspected malignant glioma or malignant peripheral nerve sheath tumor (MPNST) (excluding low-grade glioma, optic nerve glioma not requiring systemic therapy or radiotherapy); histological confirmation may be required.
• History of or concurrent other malignancies within 5 years prior to first dosing.
• Multiple factors affecting oral drug absorption (e.g., dysphagia, chronic diarrhea, intestinal obstruction, major bowel resection).
• Adverse reactions from prior anti-tumor therapy not recovered to NCI CTCAE v6.0 grade ≤1, except grade 2 alopecia, grade 2 peripheral neuropathy, grade 2 anemia, non-clinically significant and asymptomatic laboratory abnormalities, and hypothyroidism stabilized by hormone replacement therapy.
• Major surgery, significant traumatic injury, or planned major surgery during the study within 4 weeks prior to first dosing; or presence of long-term non-healed wounds or fractures.
• History of arterial/venous thrombotic events (e.g., cerebrovascular accident including transient ischemic attack (TIA), deep vein thrombosis, pulmonary embolism) or other severe thromboembolic events within 6 months prior to first dosing.
• Active viral hepatitis with poor control.
• Active syphilis requiring treatment.
• Active tuberculosis, idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonia, radiation pneumonitis requiring treatment, or clinically symptomatic active pneumonia.
• History of substance abuse that cannot be controlled or presence of psychiatric disorders.
• Planned or prior allogeneic bone marrow or solid organ transplantation.
• History of hepatic encephalopathy.
• History of or current retinal vein occlusion (RVO), retinal pigment epithelial detachment (RPED), central serous retinopathy (CSR), glaucoma, or other significant ocular abnormalities (e.g., intraocular pressure >21mmHg).
• Inability to undergo MRI and/or presence of MRI contraindications.
• Major cardiovascular disease.
• Active or uncontrolled severe infection.
• Renal failure requiring hemodialysis or peritoneal dialysis.
• History of immunodeficiency, including HIV-positive or other acquired/congenital immunodeficiency diseases.
• History of epilepsy.
• Tumor-related symptoms and treatment.
• Known hypersensitivity to study drug excipients.
• Participation in and use of other PN clinical trial drugs within 4 weeks prior to first dosing.
• Pregnant or lactating participants.
• Any other condition that, in the investigator's judgment, poses a serious risk to participant safety or interferes with study completion.