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.
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.
Single group
Amivantamab+ systemic/ intrathecal Pemetrexed
DrugAmivantamab dosing regimen: once weekly in the first month, 350 mg each time; no dosing is required in weeks 5 and 6. Starting from week 7, 700 mg each time once every 3 weeks. Systemic pemetrexed dosing regimen: day 1 of week 1, week 4, week 7 and once every 3 weeks thereafter, 500 mg/m2. Intrathecal injection shall be performed by personnel qualified to perform intrathecal injection (personnel of the Department of Radiation Oncology of our hospital holding standardized residency training certificates).
Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0"
The primary safety analysis will be conducted in subjects who develop toxicities (as defined according to CTCAE criteria). Safety will be evaluated using CTCAE version 5.0 through reported adverse events. The relationship between adverse events and the drug, time of onset, duration of the event, resolution of the event and any concomitant medication will be recorded. Adverse events (AEs) will be analyzed, including but not limited to all AEs, serious adverse events (SAEs), fatal AEs and laboratory changes.
ORR
The percentage of patients who received response after treatment accessed by RANO-LM criteria
DCR
The percentage of patients with response and SD accessed by RANO-LM criteria after treatment among the evaluable cases
Overall survival
The time from the beginning of the patient's treatment (or disease diagnosis) to death for any reason.
Progression-Free Survival
The time between the start of treatment and the progression of the tumor or the death of the patient for any reason.
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