Furmonertinib 160mg vs 80mg + Chemotherapy in EGFR-Mutated NSCLC With Brain Metastases: Efficacy and Safety Study

Официальное название

Furmonertinib 160mg Versus Furmonertinib 80mg Combined With Chemotherapy (Carboplatin + Pemetrexed) as First-Line Treatment for EGFR-Mutated NSCLC Patients With Brain Metastases: A Multicenter Study of Efficacy and Safety

Обзор

This multicenter study evaluates the efficacy and safety of furmonertinib 160mg versus furmonertinib 80mg plus chemotherapy (carboplatin + pemetrexed) as first-line treatment for EGFR-mutated NSCLC patients with brain metastases. It aims to determine which approach is more effective and safer.

Вмешательства

• Препарат Furmonertinib
  Oral administration, 160mg once daily.
• Препарат Furmonertinib
  Oral administration, 80mg once daily
• Препарат carboplatin
  Intravenous infusion, cycle-based (per study protocol).
• Препарат pemetrexed
  Intravenous infusion, cycle-based (per study protocol).

Первичные конечные точки

• Median Progression-Free Survival (PFS) as assessed by Investigator [Срок оценки: Approximately 18 months after the first patient begin study treatment]

Вторичные конечные точки (9)

• Objective Response Rate (ORR) as assessed by RECIST 1.1 [Срок оценки: Approximately 12 weeks following the first dose of study drug]
• Disease Control Rate (DCR) as assessed by RECIST 1.1 [Срок оценки: Approximately 18 months from the first patient begin study treatment]
• Central Nervous System (CNS) Objective Response Rate (CNS ORR) as assessed by RECIST 1.1 [Срок оценки: Approximately 12 weeks after the first dose of study drug]
• Central Nervous System (CNS) Disease Control Rate (CNS DCR) as assessed by RECIST 1.1 [Срок оценки: Approximately 18 months after the first dose of study drug]
• Central Nervous System Progression-Free Survival (CNS PFS) as assessed by RECIST 1.1 [Срок оценки: Approximately 18 months after the first dose of study drug]
• Median Overall Survival (OS) [Срок оценки: Approximately 24 months after the first dose of study drug]
• Safety Profile (Adverse Events, AE) as assessed by CTCAE v5.0 [Срок оценки: From the start of study drug to 28 days after the last dose of study drug]
• Progression Pattern as assessed by RECIST 1.1 and Clinical Evaluation [Срок оценки: Approximately 18 months after the first dose of study drug]
• Site Analysis of Disease Progression as assessed by RECIST 1.1 and Clinical Evaluation [Срок оценки: Approximately 18 months after the first dose of study drug]

Критерии участия

IInclusion Criteria

• Aged 18 to 75 years (male or female)
• Histopathologically confirmed, unresectable, and non-radiocurable newly -diagnosed locally advanced or metastatic lung adenocarcinoma
• Confirmed by local laboratory to have one of the following EGFR mutations: -19Del or L858R (single or mixed mutations are allowed)
• Treatment-naive for locally advanced (not suitable for surgery/radiotherapy per investigator) or metastatic NSCLC; adjuvant/neoadjuvant therapy completed >6 months before first progression is allowed (≤6 months is considered pretreated)
• At least one measurable tumor lesion per RECIST 1.1 (lesions previously treated with radiotherapy are excluded; if only one measurable lesion exists, biopsy is allowed but baseline imaging must be performed ≥14 days after biopsy)
• Confirmed stable and asymptomatic brain metastases
• Sufficient organ function (per laboratory tests): ANC ≥1.5×10⁹/L, PLT ≥100×10⁹/L, HGB ≥90g/L; TBIL ≤1.5×ULN, AST/ALT ≤2.5×ULN (for liver metastasis: TBIL ≤3×ULN, AST/ALT ≤5×ULN); CrCL ≥50 ml/min (Cockcroft-Gault formula)
• ECOG performance status 0-2 (no significant disease deterioration in 2 weeks before screening)
• Expected survival >12 weeks after first dose
• Non-pregnant women of childbearing potential (no pregnancy plan); women and men agree to use effective contraception during the study and 6 months after drug discontinuation
• Voluntarily signs informed consent and understands the study procedures Exclusion Criteria（排除标准）
• NSCLC with predominantly squamous cell histology, small cell lung cancer, neuroendocrine carcinoma, or other non-adenocarcinoma histologies
• Concurrent positive for other driver genes (ALK fusion, ROS1 fusion, RET rearrangement, BRAF mutation, NTRK fusion, MET mutation, KRAS mutation); TP53, RB1, and BRAC mutations are excluded
• Expected to receive other anti-tumor therapies during the trial
• Major surgery (except vascular access or biopsy) within 4 weeks before first dose or planned during the trial
• Use of CYP3A4 strong inhibitor within 7 days or strong inducer within 21 days before first dose; use of anti-tumor Chinese medicine within 2 weeks before first dose or planned during the trial
• Participation in other clinical trials (investigational drug/device) within 4 weeks or 5 half-lives before first dose
• Use of other anti-tumor drugs within 14 days before first dose
• Spinal cord compression or symptomatic leptomeningeal metastasis
• Toxicity from previous anti-tumor therapy not recovered to ≤CTCAE Grade 1 (except alopecia or platinum-induced peripheral neuropathy)
• Symptomatic or unstable pleural/peritoneal effusion (stable ≥14 days after drainage is allowed)
• History of other malignancies (except cured malignancies with no recurrence in 5 years: cervical carcinoma in situ, basal cell carcinoma, papillary thyroid carcinoma)
• History of interstitial lung disease (ILD), drug-induced ILD, steroid-requiring radiation pneumonitis, or suspected ILD
• Uncontrolled severe systemic diseases (e.g., hypertension, diabetes, NYHA III-IV heart failure, unstable angina, myocardial infarction within 1 year, active bleeding)
• QTc >470 msec on resting ECG
• Clinically significant QT prolongation or arrhythmias increasing QT risk (e.g., complete left bundle branch block, III° AV block, congenital long QT syndrome, severe hypokalemia, use of drugs causing QT prolongation)
• Severe gastrointestinal dysfunction that impairs drug intake or absorption Infections requiring intravenous medication
• Active mental illness or drug addiction
• Known or suspected allergy to furmonertinib or its components
• Pregnant or lactating women; women or their partners planning pregnancy during the study
• Poor compliance (unable to follow study procedures)
• Other conditions deemed unsuitable for enrollment by the investigator

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

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Tianjin Medical University Cancer Institute and Hospital — Тяньцзинь

Идентификаторы

NCT: NCT07365410 · E20250722

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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