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

Tianjin Medical University

Status and phase: Not yet enrolling; Phase 2

Conditions: Non-small Cell Lung Cancer (NSCLC); Brain Metastases; EGFR Mutation; Furmonertinib

Treatments: Drug: carboplatin; Drug: Furmonertinib; Drug: pemetrexed

Study type: Interventional

Funder types: Other

Identifiers

NCT07365410

E20250722

Details and patient eligibility

About

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Furmonertinib 160mg Group

Experimental group

Description:

Participants receive oral furmonertinib 160mg once daily as first-line treatment.

Treatment:

Drug: Furmonertinib

Drug: Furmonertinib

Furmonertinib 80mg + Chemotherapy Group

Active Comparator group

Description:

Participants receive oral furmonertinib 80mg once daily combined with intravenous carboplatin + pemetrexed (cycle-based) as first-line treatment.

Treatment:

Drug: pemetrexed

Drug: Furmonertinib

Drug: Furmonertinib

Drug: carboplatin