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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат TQ-B3234 capsules
  TQ-B3234 is an antitumor molecular targeted drug, a selective mitogen-activated protein kinase 1 and 2 (MEK1/2) inhibitor. It primarily inhibits the mitogen-activated protein kinase (MEK) protein (an upstream regulator of the extracellular signal-regulated kinase (ERK) pathway), thereby affecting the mitogen-activated protein kinase (MAPK) pathway and suppressing cell proliferation. MEK inhibitors are recognized to play a significant role in the pathogenesis of plexiform neurofibromas associated
• Препарат TQ-B3234 placebo
  TQ-B3234 placebo without drug substance.

Первичные конечные точки

• IRC-Assessed Objective Response Rate (ORR) [Срок оценки: From subject enrollment to the end of cycle 24 (each cycle is 28 days)]

Вторичные конечные точки (12)

• Investigator-Assessed ORR [Срок оценки: From subject enrollment to the end of cycle 24 (each cycle is 28 days)]
• IRC/Investigator-Assessed DOR [Срок оценки: From subject enrollment to the end of cycle 24 (each cycle is 28 days)]
• IRC/Investigator-Assessed disease control rate (DCR) [Срок оценки: From subject enrollment to the end of cycle 24 (each cycle is 28 days)]
• IRC/Investigator-Assessed progression-free survival (PFS ) [Срок оценки: From subject enrollment to the end of cycle 24 (each cycle is 28 days)]
• IRC/Investigator-Assessed TTP [Срок оценки: From subject enrollment to the end of cycle 24 (each cycle is 28 days)]
• IRC/Investigator-Assessed time to response (TTR) [Срок оценки: From subject enrollment to the end of cycle 24 (each cycle is 28 days)]
• Tumor response in subject [Срок оценки: From subject enrollment to the end of cycle 24 (each cycle is 28 days)]
• Number of subjects with incidence and severity of adverse events (AEs) [Срок оценки: From subject enrollment to the end of cycle 24 (each cycle is 28 days)]
• Patient-reported outcomes [Срок оценки: From subject enrollment to the end of cycle 24 (each cycle is 28 days)]
• Peak concentration (Cmax) [Срок оценки: 2 hours after administration]
• Plasma concentration at steady state (Ctrough, SS) [Срок оценки: Cycle 1 day 28: pre-dose, Cycle 2 day 28 pre-dose, Cycle 3 day 28: pre-dose, Cycle 6 day 28: pre-dose. (each cycle is 28 days)]
• Effects on pain score in subjects [Срок оценки: From subject enrollment to the end of the 24th cycle (each cycle is 28 days)]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 29 центров

• The First Affiliated Hospital of Anhui Medical University — Хэфэй
• Peking Union Medical College Hospital — Пекин
• Xuanwu Hospital Capital Medical University — Пекин
• Beijing Tiantan Hospital, Capital Medical University — Пекин
• Peking University Third Hospital — Пекин
• The Southwest Hospital of Amu — Чунцин
• The First Affiliated Hospital of Fujan Medical University — Фучжоу
• Gansu Provincial Cancer Hospital — Lanzhou
• … и ещё 21 центр

Идентификаторы

NCT: NCT07407803 · TQ-B3234-III-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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