This is a prospective, open-label, multi-center, single-arm clinical trial

The purpose of this study is to assess the efficacy and safety of sac-TMT combined with third-generation EGFR-TKI with/without intracranial radiotherapy in subjects with EGFR-mutated NSCLC and brain metastasis who have failed prior EGFR-TKI treatment. Eligible subjects will receive sac-TMT (4 mg/kg, twice weekly (Q2W)) + third-generation EGFR-TKI ± intracranial radiotherapy. The decision to initiate intracranial radiotherapy will be determined by the investigator based on the patient's clinical condition.

Inclusion Criteria:

• Age ≥ 18 and ≤ 75 years at the time of signing the informed consent form (ICF), regardless of gender;
• Histologically or cytologically confirmed non-squamous NSCLC, and metastatic (Stage IV);
• Confirmed EGFR sensitizing mutation including exon 19 deletion (19-Del) or exon 21 point mutation (L858R);
• Subject has previously received EGFR-TKI therapy for locally advanced or metastatic disease and has experienced radiological PD;
• Subjects with new or previously diagnosed brain metastasis confirmed by contrast-enhanced cranial MRI;
• ECOG performance status scale of 0 or 1;
• Life expectancy ≥ 12 weeks;
• Adequate organ and bone marrow function;

Exclusion Criteria:

• Tumor histology or cytology confirms combined small cell lung cancer (SCLC), neuroendocrine carcinoma, carcinosarcoma components, or squamous cell carcinoma;
• Known leptomeningeal metastases;
• Other malignant tumors within 3 years prior to the first dose (except for tumors cured by local treatment, such as basal cell carcinoma of skin, squamous cell carcinoma of skin, cervical carcinoma in situ, etc.);
• Has uncontrolled, significant cardiovascular disease or cerebrovascular disease including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to >470 ms, and other serious cardiovascular and cerebrovascular diseases within 6 months before study intervention;
• Uncontrolled systemic diseases as judged by the investigators;
• Clinically severe pulmonary impairment due to concurrent lung disorders, including but not limited to any underlying lung disorder (e.g., pulmonary embolism within 3 months before the first dose, severe asthma, severe chronic obstructive pulmonary disease, restrictive pulmonary disease, pleural effusion, etc.) or any autoimmune, connective tissue, or inflammatory disease that may involve the lungs (i.e., rheumatoid arthritis, sicca syndrome, sarcoidosis, etc.), or prior pneumonectomy;
• Subjects with active chronic inflammatory bowel disease, gastrointestinal obstruction, severe ulcer, gastrointestinal perforation, intra-abdominal abscess, or acute gastrointestinal hemorrhage;
• History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease;
• Active infection requiring systemic therapy;
• Active hepatitis B [hepatitis B surface antigen (HBsAg) positive, requiring hepatitis B virus deoxyribonucleic acid (HBV-DNA) testing; HBV-DNA ≥500 IU/mL or above the lower limit of detection, whichever is higher] or hepatitis C [hepatitis C antibody positive, and hepatitis C virus ribonucleic acid (HCV-RNA) above the lower limit of detection];
• Positive human immunodeficiency virus (HIV) test or history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection;
• History of allogeneic tissue/solid organ transplant.