High-dose Furmonertinib for First-line Treatment of EGFR Mutated NSCLC With Central Nervous System (CNS) Metastases

Inclusion Criteria:

• Signed written informed consent before any study-related procedure.

• Age ≥ 18 years.

• ECOG PS of 0 to 1 at screening,and with no clinically significant deterioration inthe previous 2 weeks.

• Expected survival ≥12 weeks.

• Histologically or cytologically confirmed metastatic Non-Small Cell Lung Cancer (International Association for the Study of Lung Cancer and Joint Committee on theAmerican Classification of Cancer, TNM Lung cancer stage 8). Documented validatedresults from local testing of either tumor tissue or blood confirming the presenceof EGFR 19del or exon 21del L858R mutation. These mutations above may exist alone ortogether.

• According to RECIST 1.1, patients must have at least one central nervous system (CNS) metastatic tumor lesion at baseline that meets the following requirements:accurately and repeatably measurable at baseline, have no radiotherapy or biopsy.

• Patients who have untreated for advanced/metastatic non-small cell lung cancer,including chemotherapy, biological therapy, targeted therapy, immunotherapy, orexperimental therapy, prior to initiation of study drug therapy. Patients who havereceived adjuvant therapy or neoadjuvant therapy (chemotherapy and/or radiotherapy)are allowed to enroll if there is no progression within 6 months of treatment.Patients who have received topical therapy (radiotherapy or perfusion therapy) areallowed to enroll if the lesion within the local therapeutic area is non-targeted.

• For premenopausal women with childbearing potential, a pregnancy test must beperformed within 14 days before the first dose, and the pregnancy test (blood orurine test) must be negative; female subjects must not be lactating;

• Willing to use contraception.

• Voluntary and agree to follow the study treatment protocol as well as follow-upplan, and can accept the oral medicine treatment.

Exclusion Criteria:

• Small cell lung carcinoma;

• History of hypersensitivity to active or inactive excipients of investigationalagent with a similar chemical structure.

• Confirmed EGFR 20 exon insertion mutations at any time after the initial diagnosis.

• Patient who receive prior treatment including any of the following:

• Any Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI).

• The patients who have received intrapleural perfusion therapy can only be enrolled 28 days or more after the pleural effusion is stable;

• Major surgery within 4 weeks of the first dose of investigational agent.

• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field ofradiation within 4 weeks of the first dose of investigational agent;

• CYP3A4 strong inhibitor or strong inducer is used within 7 days prior to the firstdose, or need to receive these drugs during the study period.

• Traditional Chinese medicine and traditional Chinese medicine preparations withanti-tumor as indications and with adjuvant treatment of tumor is used within 7 daysprior to the first dose, or need to receive these drugs during the study period.

• Patients who are receiving drugs known to prolong QTc interval or may cause torsadede pointe and need to continue to receive these drugs during the study period.

• The time from the treatment with any other investigational product or its analogueto the first dose does not exceed 5 half-lives of the drug or 14 days, whichever islonger.

• Prior treatment with any systemic anti-cancer therapy for advanced Non-Small CellLung Cancer (NSCLC) including chemotherapy, biologic therapy, target therapy,immunotherapy, or any investigational drug, except neoadjuvant or adjuvant therapybefore 6 months prior to the first dose investigational treatment.

• At the beginning of study treatment, any unresolved toxic reaction to priortreatment is present, which exceeds Grade 1 in accordance with Common TerminologyCriteria for Adverse Events (CTCAE) (except for alopecia), and exceeds Grade 2 forprior platinum treatment-related neuropathy.

• Spinal cord compression; symptomatic and unstable brain metastases, except for thosepatients who have completed definitive therapy, are not on steroids, and have astable neurological status for at least 2 weeks after completion of the definitivetherapy and steroids.

• Diagnosed other malignant tumors or had a history of other malignant tumors in last 5 years, except for skin basal cell carcinoma, cervical carcinoma in situ and breastductal carcinoma in situ which have been effectively controlled;

• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability toswallow the formulated product, or previous significant bowel resection that wouldpreclude adequate absorption of investigational agent.

• Any evidence of severe or uncontrolled systemic diseases, including uncontrolledhypertension, active bleeding diatheses, and active infection, which in theInvestigator's opinion makes it undesirable for the patient to participate in thetrial.

• Past medical history of Interstitial Lung Disease (ILD), drug-induced InterstitialLung Disease, radiation pneumonitis that required steroid treatment, or any evidenceof clinically active Interstitial Lung Disease.

• Any evidence of corneal injury:

• Inadequate bone marrow reserve or organ function.

• QT prolongation or any clinically important abnormalities in rhythm and heartfunction.

• Patients who may have poor compliance with the research procedures and requirements,etc., as judged by investigators.

• Pregnancy or lactation.