A Single-Arm Phase II Exploratory Clinical Study of Amivantamab Combined With Intrathecal Pemetrexed for Leptomeningeal Metastasis From EGFR-Mutated Lung Adenocarcinoma
The goal of this clinical trial is to learn whether amivantamab combined with intrathecal pemetrexed is safe and may help treat leptomeningeal metastasis in adults with EGFR-mutant lung adenocarcinoma. Leptomeningeal metastasis occurs when cancer cells spread to the membranes surrounding the brain and spinal cord or to the cerebrospinal fluid. It is a serious complication of advanced lung cancer and is difficult to treat because many systemic drugs do not reach high enough levels in the cerebrospinal fluid. The main questions this study aims to answer are: What medical problems do participants have when receiving amivantamab combined with intrathecal pemetrexed? How long do participants live without their disease getting worse after receiving this treatment? How long do participants survive after starting this treatment? Participants will: Receive amivantamab by intravenous infusion according to the study schedule. Receive intrathecal pemetrexed, together with dexamethasone and normal saline, once every week. Continue their original EGFR tyrosine kinase inhibitor treatment as determined by the study doctor. Have cerebrospinal fluid pressure measured and cerebrospinal fluid samples collected before each intrathecal treatment. Have tests of cerebrospinal fluid, including routine tests, biochemical tests, tumor markers, albumin, IgG, and cytology. Have imaging tests, including enhanced MRI, about every 3 months to check the disease. Be followed by clinic visits and/or telephone calls to collect information about survival, disease status, side effects, and any later cancer treatments.
• 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.