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

Official title

A Single-Arm Phase II Exploratory Clinical Study of Amivantamab Combined With Intrathecal Pemetrexed for Leptomeningeal Metastasis From EGFR-Mutated Lung Adenocarcinoma

Overview

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.

Interventions

• Drug Amivantamab+ systemic/ intrathecal Pemetrexed
  Amivantamab 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 certi

Primary outcome measures

• Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0" [Time frame: 2 year]

Secondary outcome measures (8)

• ORR [Time frame: 2 year]
• DCR [Time frame: 2 year]
• Overall survival [Time frame: 2 year]
• Progression-Free Survival [Time frame: 2 year]
• 3-month OS rate [Time frame: 3 months]
• 6-month OS rate [Time frame: 6 months]
• 9-month OS rate [Time frame: 9 months]
• 1-year OS rate [Time frame: 1 year]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The Second Affiliated Hospital,School of Medicine,Zhejiang University — Hangzhou

Identifiers

NCT: NCT07744529 · Y2026-0871

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗