Amivantamab Combined With Intrathecal Pemetrexed for LM From EGFR-Mutated Lung Adenocarcinoma

Inclusion criteria

• Voluntary participation in the clinical study: fully understands and is informed of this study and signs the written informed consent form; is willing and able to complete all trial procedures.
• Age: >=18 years; male or female.
• Patients with EGFR-mutated lung adenocarcinoma with leptomeningeal metastasis diagnosed according to the EANO-ESMO guidelines.
• Expected survival of at least 3 months.
• Adequate organ and bone marrow function, with no severe hematopoietic abnormality and no severe cardiac, pulmonary, hepatic or renal dysfunction or immunodeficiency (within 14 days before use of study drug, no blood transfusion, granulocyte colony-stimulating factor or other relevant medical support):

• Complete blood count: absolute neutrophil count (ANC) >=1.5 x 10^9/L (1500/mm^3), platelets >=75 x 10^9/L, hemoglobin >=9 g/dL (if bone marrow is involved, platelets >=50 x 10^9/L, ANC >=1.0 x 10^9/L and hemoglobin >=8 g/dL).
• Liver function: serum bilirubin <=1.5 x upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=1.5 x ULN (if there is liver involvement, AST and ALT <=5 x ULN are allowed).
• Renal function: serum creatinine <=1.5 x ULN.
• Coagulation function: INR <=1.5 x ULN; PT and APTT <=1.5 x ULN (unless the subject is receiving anticoagulant therapy and PT and APTT are within the expected range of anticoagulant treatment at screening).
• Left ventricular ejection fraction (LVEF) in cardiac function examination >=50%.
• Negative serum pregnancy test, and effective contraception from signing the informed consent form until 6 months after the last chemotherapy dose.
• Thyroid-stimulating hormone (TSH), free thyroxine (FT4) or free triiodothyronine (FT3) within +/-10% of the normal range.
• Ophthalmic examination, including dilated fundus examination, slit-lamp examination and color fundus photography.

Exclusion criteria

• Currently participating in another clinical study, or less than 4 weeks between the first dose of the study drug and the end of treatment in a previous clinical study.
• History of other malignancies within the past 5 years.
• Patients who have received CNS-directed prophylactic treatment.
• Patients with known history of human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome.
• Patients with active autoimmune disease or a history of autoimmune disease with a high risk of recurrence, including but not limited to immune-related neuropathy, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis, systemic lupus erythematosus, connective tissue disease, scleroderma, inflammatory bowel cancer (including Crohn disease and ulcerative colitis), autoimmune hepatitis, toxic epidermal necrolysis or Stevens-Johnson syndrome.
• Patients with active chronic hepatitis B or active hepatitis C. Patients who are positive for hepatitis B surface antigen or hepatitis C virus antibody during screening may be enrolled only after further HBV DNA titer testing (not higher than 1000 IU/mL) and HCV RNA testing (not exceeding the lower limit of detection of the assay), and after active hepatitis B or hepatitis C infection requiring treatment has been excluded. Hepatitis B virus carriers, patients with stable hepatitis B after drug treatment and patients with cured hepatitis C may be enrolled.
• Active pulmonary tuberculosis.
• Current interstitial lung disease or infectious pneumonia.
• Active infection requiring systemic anti-infective therapy, including but not limited to bacterial, fungal or viral infection.
• Within 6 months before screening, New York Heart Association (NYHA) class III or IV heart failure, unstable angina, severe poorly controlled ventricular arrhythmia, or electrocardiographic evidence of acute ischemia or myocardial infarction.
• QTcF interval >480 msec, unless secondary to bundle branch block.
• Uncontrolled comorbid disease, including but not limited to uncontrolled hypertension, active peptic ulcer or bleeding disorder.
• History of psychiatric illness; incapacity or limited capacity for civil conduct.
• In the judgment of the investigator, the patient's underlying condition may increase the risk of receiving study drug treatment or confound the occurrence and assessment of toxic reactions.
• Other patients whom the investigator considers unsuitable for participation in this study.