Furmonertinib Combined With Intrathecal Chemotherapy and Stereotactic Radiotherapy (SRT) for EGFR-Mutated NSCLC Patients With Brain Parenchymal and Leptomeningeal Metastases

NCT07304739 | Recruiting Phase 2 DMC

• 1 other identifier: E20250589
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

A Single-Arm Clinical Study of Furmonertinib (160mg) Combined with Intrathecal Chemotherapy (ITC) and Stereotactic Radiotherapy (SRT) as First-Line Treatment in EGFR Classic Mutation-Positive NSCLC Patients with Brain Parenchymal and Leptomeningeal Metastases

Conditions

Non Small Cell Lung Cancer

Keywords

NSCLC; EGFR mutation; Brain parenchymal and meningeal metastases; Furmonertinib; Intrathecal chemotherapy; Stereotactic radiotherapy

Outcome Measures

Primary Outcomes (1)

• iPFS

  iPFS is defined as the time from the start of treatment to the occurrence of intracranial disease progression (excluding non-intracranial progression) or death

  From enrollment to the occurrence of intracranial disease progression (excluding non-intracranial progression) or death，assessed up to 2 year

Secondary Outcomes (5)

• PFS

  from the start of treatment to the occurrence of tumor progression or all-cause death, assessed up to 2 year

• OS

  from the start of treatment to death, 2 years

• LM remission rate

  Until the end of the study, 1year

• iORR

  From enrollment to the end of treatment at 1 year

• iDCR

  From enrollment to the end of treatment at 1year

Study Arms (1)

Furmonertinib combined with intrathecal chemotherapy and stereotactic radiotherapy group

EXPERIMENTAL

Drug: Furmonertinib; Drug: Intrathecal chemotherapy; Radiation: Stereotactic radiotherapy

Interventions

Furmonertinib DRUG

Furmonertinib: 160mg, once daily, orally.

Furmonertinib combined with intrathecal chemotherapy and stereotactic radiotherapy group

Intrathecal chemotherapy DRUG

Intrathecal chemotherapy with 40mg of pemetrexed and 2mg of dexamethasone, every 3 weeks as one cycle.

Furmonertinib combined with intrathecal chemotherapy and stereotactic radiotherapy group

Stereotactic radiotherapy RADIATION

After two cycles of intrathecal chemotherapy, there was no progression upon re-examination. The stereotactic radiotherapy (SRT) for brain metastases with 7-19Gy/1-5Fx.

Furmonertinib combined with intrathecal chemotherapy and stereotactic radiotherapy group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to 75 years old, male or female;
• Histopathologically confirmed, unresectable, and not amenable to curative radiotherapy treatment-naïve locally advanced or metastatic lung adenocarcinoma;
• The patient was confirmed by a local laboratory to have one of the following EGFR mutations :19Del or L858R;
• The patient has not received any systemic anti-tumor treatment in the locally advanced (the researcher judged that it was not suitable for surgery or radiotherapy) or metastatic NSCLC;
• At least one measurable tumor lesion (according to RECIST1.1);
• Confirm the simultaneous presence of brain parenchymal and meningeal metastasis;
• Laboratory tests indicated that the subjects had adequate organ functions, including: 1) ANC ≥1.5×109/L; PLT ≥100×109/L; HGB ≥90g/L; 2) TBIL ≤1.5 times the upper limit of the normal value, AST and ALT ≤2.5 times the upper limit of the normal value (for those with liver metastasis, total bilirubin ≤ 3 times the upper limit of the normal value, AST and ALT≤ 5 times the upper limit of the normal value are allowed); 3) CrCL ≥50 ml/min (calculated according to the Cockcroft-Gault formula);
• The ECOG score at the time of screening was 0-2, and there was no significant deterioration of the disease within 2 weeks before the screening;
• The expected survival period is greater than 12 weeks;
• Non-pregnant female patients of childbearing potential with no pregnancy plan. Female subjects of childbearing potential and male subjects must agree to use effective contraception during the study period and for 6 months after discontinuation of the study drug;
• Understand and voluntarily participate in this study and sign the informed consent form.

You may not qualify if:

• Histological or cytological examination suggests NSCLC dominated by squamous cells, or indicates the presence of small cell lung cancer, neuroendocrine carcinoma, etc.；
• Patients with other driver genes: ALK, ROS1, RET, BRAF, NTRK, MET, KRAS, etc.. But TP53, RB1, BRAC are not included；
• Anticipated requirement for other antitumor therapies beyond this clinical trial during the study period;
• Having received any of the following treatments: a) Major surgery within 4 weeks prior to the first dose or during the trial period, excluding procedures such as vascular access establishment, mediastinoscopy, or thoracoscopy for biopsy; b) Use of strong CYP3A4 inhibitors within 7 days or strong CYP3A4 inducers within 21 days prior to the first dose; Use of Chinese herbal medicines or preparations with anti-tumor indications or those adjunctive to cancer therapy within 2 weeks prior to the first dose or expected during the trial period; c) Participation in an investigational drug or device clinical trial within 4 weeks or at least 5 half-lives (whichever is longer) prior to the first dose; d) Treatment with other antitumor drugs within 14 days prior to the first dose;
• Patients with symptomatic and unstable pleural or peritoneal effusion; those who have achieved clinical stability for at least 14 days after drainage of pleural effusion or ascites may be enrolled;
• Toxicities from prior antitumor therapy have not recovered to ≤ CTCAE grade 1(with the exception of alopecia and residual neurotoxicity from previous platinum-based therapy)；
• History of other malignancies or currently concurrent other malignancies (except for malignancies that have undergone radical resection with no recurrence within 5 years, such as cervical carcinoma in situ, basal cell carcinoma of the skin, and papillary thyroid carcinoma);
• History of interstitial lung disease (ILD), drug-induced ILD, or radiation pneumonitis requiring steroid treatment; or current clinical manifestations suggestive of ILD;
• Severe or uncontrolled systemic diseases requiring treatment including hypertension, diabetes, chronic heart failure (NYHA class III-IV), unstable angina, myocardial infarction within the past year, active hemorrhagic conditions, severe gastrointestinal disorders, active infectious diseases, etc.;
• Resting QT interval (QTc) \> 470 msec as measured by clinical ECG screening; Clinically significant prolonged QT interval or other arrhythmias or clinical conditions that may increase the risk of QT prolongation;
• Known history of psychiatric disorders or drug abuse, with current active symptoms or ongoing drug use;
• Known or suspected hypersensitivity to furmonertinib or any excipients of its formulation;
• Female subjects who are pregnant or breastfeeding, or female partners of male subjects who plan to become pregnant during the study period;
• The subject demonstrated poor compliance;
• Any other condition deemed by the investigator to make the subject unsuitable for participation in this study.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (3)

CANGZHOU People's Hospital

Cangzhou, Hebei, 061001, China

RECRUITING

Tianjin medical university cancer hospital and institute

Tianjin, Tianjin Municipality, 300060, China

RECRUITING

Tianjin Huanhu Hospital

Tianjin, Tianjin Municipality, 300350, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Meningeal Carcinomatosis

Interventions

aflutinib; Radiosurgery

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Maobin Meng

  Tianjin Medical University Cancer Institute and Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maobin Meng, MD

CONTACT

+86 15202231270; mmeng@tmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2025
• First Posted: December 26, 2025
• Study Start: December 22, 2025
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2029
• Last Updated: December 26, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)