leptomeningeal metastases patients with EGFR mutation-positive NSCLC
Conditions
Interventions
Interventional group:zorifertinib combined with furmonertinib
Sponsors
Nanjing Brain Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. The subject has fully understood this study and voluntarily signed the Informed Consent Form (ICF). 2. The subject must be >=18 years of age prior to signing the Informed Consent Form (ICF). 3. During the screening phase, the subject must have a prior histological or cytological diagnosis of NSCLC with an EGFR sensitizing mutation (including L858R and/or Exon19Del). 4. Subjects who have developed leptomeningeal metastasis following treatment with third-generation EGFR-TKIs (either as monotherapy or in combination with conventional therapies, provided that any concurrent conventional therapy has been washed out for at least 2 weeks) and who have no extracranial disease progression are eligible. 5. Subjects must have a confirmed diagnosis of leptomeningeal metastasis based on the "EANO-ESMO" diagnostic criteria, assessed comprehensively through clinical evaluation, including symptom assessment, imaging assessment, and/or cerebrospinal fluid (CSF) pathological evaluation. 6. Subjects with concurrent leptomeningeal and parenchymal brain progression are eligible for enrollment. 7. If neurological symptoms are present, the following criteria must be met: At least 1 week prior to study treatment, no increase in corticosteroid dose is required to control central nervous system symptoms. If the patient is receiving corticosteroids for the purpose of treating endocrine dysfunction or tumor-related symptoms (non-CNS related), the dose must remain stable or be reduced within 5 days prior to study drug administration. Note: Corticosteroid dosage must be stable for 5 days prior to baseline brain MRI. 8. All toxicity related to prior anti-tumor therapy (including radiotherapy) must have resolved to =1.5 x 10^9/L (2) Platelet count >=100 x 10^9/L (3) Hemoglobin >=90 g/L (4) Serum creatinine =50 mL/min (5) Total bilirubin =3 months. 11. Karnofsky Performance Status (KPS) score >=40.
Exclusion criteria
Exclusion criteria: 1. Subjects with a history of radiotherapy within 28 days prior to study drug administration are ineligible. Palliative radiotherapy to bone within 14 days prior to study drug administration is also not permitted. 2. Subjects who have undergone major surgery (e.g., thoracic, abdominal, or pelvic surgery) within 4 weeks prior to the first dose of study treatment, or who have not yet recovered from related surgical adverse effects, are ineligible. 3. Subjects with other concurrent malignancies, or a history of any other malignancy within the past 5 years, are ineligible, except for completely resected basal cell or squamous cell carcinoma of the skin, or completely resected in situ carcinoma of any type. 4. Subjects with clinically significant, uncontrolled cardiac disease and/or any cardiac event within the past 6 months are ineligible, including: (1) Unstable angina within 6 months prior to screening; (2) Myocardial infarction within 6 months prior to screening; (3) Documented history of heart failure (NYHA Class III–IV); (4) Uncontrolled hypertension: systolic blood pressure >=160 mmHg and/or diastolic blood pressure >=100 mmHg, with or without antihypertensive medication (adjustment of antihypertensive drugs prior to screening is permitted); (5) Ventricular arrhythmias; (6) Supraventricular or sinus arrhythmias that are poorly controlled by medication; (7) Other arrhythmias not controlled by medication; (8) QTcF >470 ms (average of three measurements corrected using Fridericia’s formula) during screening; (9) Left ventricular ejection fraction (LVEF) <50%. 5. Subjects with gastrointestinal disease or severe gastrointestinal dysfunction that may significantly impair drug absorption (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome) are ineligible. 6. Subjects must not use the following drugs within 1 week prior to study drug administration and throughout the study period: (1) Strong CYP3A4 inducers or inhibitors; (2) Drugs primarily metabolized by CYP3A4; (3) Drugs known to prolong the QT interval or cause torsades de pointes. 7. Subjects with a history of or concurrent HIV infection are ineligible. Subjects who are HCV antibody-positive may be enrolled if HCV-RNA is undetectable (using the lower limit of detection defined by each center’s assay) and without concurrent hepatitis B virus (HBV) infection. HBV-infected subjects may be enrolled if they meet the following criteria: 1) For active hepatitis B: at least 6 weeks of antiviral therapy prior to study treatment initiation, HBV DNA <100 IU/mL, and ALT and AST levels <ULN; 2) For resolved or chronic hepatitis B: prophylactic antiviral therapy for at least 2–4 weeks prior to study treatment initiation, HBV DNA <100 IU/mL (e.g., in inactive carrier state), and ALT and AST levels <ULN. 8. Pregnant or lactating women are ineligible. Women of childbearing potential must use highly effective contraception during treatment and for 3 months after the last dose. Sexually active men capable of fathering a child must use highly effective contraception during treatment and for 6 months after the last dose. 9. Subjects with other serious acute or chronic medical conditions, such as uncontrolled diabetes, psychiatric disorders, or abnormal laboratory findings, that, in the investigator’s judgment, may increase the risk to the subject or complicate interpretation of study results, are ineligible. 10. Subjects with
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Leptomeningeal Progression-Free Survival (LmPFS); | — |
Secondary
| Measure | Time frame |
|---|---|
| Changes in Karnofsky Performance Status (KPS) score;Improvement in central nervous system symptoms;Safety Parameters;Time to Treatment Discontinuation;Cerebrospinal fluid (CSF) response rate;Leptomeningeal ORR;Overall Survival (OS);Neurological function improvement;Overall Progression-Free Survival; | — |
Countries
China
Contacts
Public ContactFang Shencun
Nanjing Brain Hospital
Outcome results
None listed