Firmonertinib Combined With Intrathecal Injection for the Treatment of EGFR Mutant NSCLC With Leptomeningeal Metastases

Launched by UNION HOSPITAL, TONGJI MEDICAL COLLEGE, HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY · Jul 27, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for people with a specific type of lung cancer called non-small cell lung cancer (NSCLC) that has spread to the lining around the brain and spinal cord, known as leptomeningeal metastases (LM). The treatment combines a high dose of a drug called Firmonertinib with injections directly into the fluid around the brain and spine (intrathecal injection). The study also aims to see if testing cancer DNA found in the spinal fluid can help doctors better monitor how well the treatment is working.

People who may be eligible to join are adults with advanced NSCLC that has certain genetic changes (EGFR mutations) and who have already tried other standard treatments without success. Participants need to be in reasonable health to undergo the treatment and the necessary spinal fluid testing. During the trial, patients will receive the Firmonertinib treatment along with spinal injections and have regular tests to check their response to therapy. This study is important because it explores a promising new treatment option and a way to closely track how the cancer responds, which could improve care for patients facing this challenging condition.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Obtain an informed consent form signed by the patient or their legal representative;
• • Age greater than or equal to 18 years old;
• • According to the 9th edition TNM staging of lung cancer by the International Association for the Study of Lung Cancer and the Joint Committee on Cancer Staging in the United States, metastatic (stage IV) NSCLC with histological or cytological confirmation;
• • Confirmed by histological or cytological specimens tested in the central laboratory to have EGFR exon 19 deletion mutation (19DEL) or exon 21 L858R point mutation (L858R), which can exist alone or in combination;
• • ECOG physical condition score is 0-3 points, with an expected life expectancy of ≥ 12 weeks;
• • According to the criteria for evaluating the efficacy of solid tumors (RECIST 1.1), there should be at least one measurable lesion;
• • According to the "EANO-ESMO" diagnostic criteria for meningeal metastasis (Type I: positive cerebrospinal fluid cytology or biopsy; Type II: limited to typical clinical symptoms and neuroimaging findings), for clinical judgment. Patients with leptomeningeal metastases who can be included in the study are type I patients and type II patients with EGFR mutations in cerebrospinal fluid ctDNA; merged brain parenchymal metastases can also be included in the study;
• • Progress in first-line treatment with first and second-generation EGFR-TKI;
• • Progress in first-line conventional dose treatment with third-generation EGFR-TKI;
• • The subject must accept and be able to cooperate with the lumbar puncture procedure, and confirm that there are no contraindications to chemotherapy or lumbar puncture;
• • At least 4 weeks before treatment, all extracranial symptoms must be stable, and there must be no CNS complications requiring emergency neurosurgical intervention.
• Exclusion Criteria:
• • Squamous cell carcinoma of the lung;
• • Known history of hypersensitivity reactions to drugs with or without active excipients or similar structures or categories to the investigational drug for famotinib/pemetrexed;
• • Confirmed EGFR exon 20 insertion mutation;
• • At the beginning of drug treatment, if the toxicity associated with previous anti-tumor therapy has not recovered to ≤ CTCAE Grade 1, except for peripheral neurotoxicity caused by hair loss or chemotherapy ≤ CTCAE Grade 2;
• • Excluding skin basal cell carcinoma, cervical carcinoma in situ, and ductal carcinoma of the breast that have been effectively controlled and have been diagnosed with other malignant tumors or have a history of other malignant tumors in the past 5 years;
• • Patients who are deemed ineligible by researchers to participate in this study, such as those who are highly likely to be unable to comply with the study protocol, constraints, and requirements, or other situations determined by the researcher at their discretion;
• • Pregnancy or lactation.