Brain Metastases, EGFR Mutation, Furmonertinib, Non-small Cell Lung Cancer (NSCLC)
Conditions
Brief summary
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.
Interventions
DRUGFurmonertinib
Oral administration, 160mg once daily.
DRUGcarboplatin
Intravenous infusion, cycle-based (per study protocol).
DRUGpemetrexed
Intravenous infusion, cycle-based (per study protocol).
Sponsors
Tianjin Medical University Cancer Institute and Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression-Free Survival (PFS) as assessed by Investigator | Approximately 18 months after the first patient begin study treatment | The time from the first dose of the study drug to the progression of the disease (Investigator-Assessed) or death for any reason according to investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) as assessed by RECIST 1.1 | Approximately 12 weeks following the first dose of study drug | Proportion of subjects whose tumors were assessed as complete response(CR) or partial response(PR) according to RECIST 1.1. |
| Disease Control Rate (DCR) as assessed by RECIST 1.1 | Approximately 18 months from the first patient begin study treatment | Proportion of subjects whose tumors were assessed as CR, PR or stable disease (SD) according to RECIST 1.1. |
| Central Nervous System (CNS) Objective Response Rate (CNS ORR) as assessed by RECIST 1.1 | Approximately 12 weeks after the first dose of study drug | Proportion of subjects whose central nervous system (CNS) tumors (including intracranial parenchymal metastases and asymptomatic meningeal metastases as defined in the inclusion criteria) are assessed as Complete Response (CR) or Partial Response (PR) according to RECIST1.1. |
| Central Nervous System (CNS) Disease Control Rate (CNS DCR) as assessed by RECIST 1.1 | Approximately 18 months after the first dose of study drug | Proportion of subjects whose central nervous system (CNS) tumors (including intracranial parenchymal metastases and asymptomatic meningeal metastases as defined in the inclusion criteria) are assessed as Complete Response (CR), Partial Response (PR), or Stable Disease (SD) according to RECIST 1.1. |
| Central Nervous System Progression-Free Survival (CNS PFS) as assessed by RECIST 1.1 | Approximately 18 months after the first dose of study drug | The time from the first dose of the study drug (Furmonertinib) to the first occurrence of central nervous system (CNS) disease progression (assessed by RECIST 1.1) or death from any cause, whichever comes first. |
| Median Overall Survival (OS) | Approximately 24 months after the first dose of study drug | The time from the first does of the study drugs to the death for any reason |
| Safety Profile (Adverse Events, AE) as assessed by CTCAE v5.0 | From the start of study drug to 28 days after the last dose of study drug | The number of patients with adverse events and the severity grading (Grade 1-5) according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. |
| Progression Pattern as assessed by RECIST 1.1 and Clinical Evaluation | Approximately 18 months after the first dose of study drug | Proportion of subjects with first disease progression classified as Intracranial, extracranial, or combined intracranial-extracranial progression. |
| Site Analysis of Disease Progression as assessed by RECIST 1.1 and Clinical Evaluation | Approximately 18 months after the first dose of study drug | Frequency of specific progression sites. |
Countries
China
Contacts
CONTACTDingzhi Huang Huang
Outcome results
None listed