Inclusion Criteria:
1. Age ≥ 18 and ≤80 when signing the informed consent form, regardless of gender;
2. Histologically or cytologically confirmed nonsquamous NSCLC with EGFR-sensitive
mutation (exon 19 deletion or exon 21 L858R mutation).
3. Progression on or after 3rd-generation EGFR-TKI (change to the third-generation
EGFR-TKIs after receiving 1st or 2nd generations of TKI, or to use the
third-generation TKI in the first line are all allowed).
4. Brain parenchymal metastases confirmed by cranial MRI, including asymptomatic BM or
those with symptoms controlled after local treatment and/or dehydration therapy,
should maintain a clinically stable state (no longer requiring glucocorticoids or
anticonvulsants) for at least 2 weeks before the first dose.
5. According to mRECIST 1.1, the subject must have at least one accurately measurable
intracranial target lesion that has not been previously treated with local therapies
such as radiation therapy or surgery. Brain metastatic lesions with a diameter of ≥
5 mm are permitted to be designated as target lesions.
6. ECOG PS 0-1.
7. Estimated life expectancy of 12 weeks or more.
8. Adequate organ function.
9. Female subjects of childbearing potential and male subjects whose partners are of
childbearing potential must agree to use effective medical contraceptive measures
from the time of signing the informed consent form until 6 months after the last
dose.
10. The subject voluntarily participates in this study, signs the informed consent form,
and is able to comply with the study visits and related procedures as specified in
the protocol.
Exclusion Criteria:
1. Histologically or cytologically confirmed tumor with components of small cell lung
cancer, neuroendocrine carcinoma, carcinosarcoma, or squamous cell carcinoma;
2. Patients with spinal cord compression or those assessed by the investigator as
having extensive meningeal metastasis;
3. Previous whole-brain radiotherapy for brain metastases;
4. Subjects who have previously received chemotherapy, TROP2-targeted therapy, or any
drug therapy containing topoisomerase I inhibitors, including antibody-drug
conjugate (ADC) therapy (including in the context of adjuvant or neoadjuvant
therapy);
5. Tumor invading or surrounding important surrounding organs and blood vessels (such
as the heart, esophagus, superior vena cava, etc.), or with obvious necrosis,
cavitation, or at risk of developing esophagotracheal fistula or esophagopleural
fistula;
6. A history of bleeding tendency or coagulation disorder and/or clinically significant
bleeding symptoms or risks within 4 weeks before the first dose;
7. Use of aspirin (> 325 mg/day) or treatment with dipyridamole or clopidogrel within 2
weeks before the first dose;
8. Use of full-dose oral or intravenous anticoagulants or thrombolytics within 2 weeks
before the first dose;
9. Biopsy or other minor surgeries (excluding placement of vascular access devices)
within 7 days before the first dose;
10. Presence of non-healing wounds or untreated fractures (excluding old fractures and
other fractures that do not require treatment);
11. History of other malignant tumors within 3 years before the first dose (except
tumors cured by local treatment, such as cutaneous basal cell carcinoma, cutaneous
squamous cell carcinoma, cervical carcinoma in situ, etc.);
12. Presence of any of the following cardiovascular and cerebrovascular diseases or risk
factors:
1. Myocardial infarction, unstable angina pectoris, acute or persistent myocardial
ischemia, grade 3 or 4 heart failure (according to the New York Heart
Association (NYHA) classification), symptomatic or poorly controlled severe
arrhythmia, cerebrovascular accident, transient ischemic attack, or other
severe cardiovascular and cerebrovascular diseases within 6 months before the
first dose;
2. Previous history of myocardial diseases such as myocarditis, primary
cardiomyopathy, or specific cardiomyopathy;
3. Any deep vein thrombosis within 3 months before the first dose (subjects with
stable condition after treatment with low-molecular-weight heparin or drugs
with similar effects for ≥ 2 weeks are permitted to enroll), peripheral
arterial thromboembolic events, pulmonary embolism, or other severe
thromboembolic events;
4. Presence of major vascular diseases that may be life-threatening or require
surgery within 6 months before the first dose, such as aortic aneurysm or
aortic dissecting aneurysm;
13. Uncontrolled systemic diseases as judged by the investigator:
14. History of (non-infectious) interstitial lung disease (ILD) or non-infectious
pneumonia requiring steroid treatment, current ILD or non-infectious pneumonia, or
suspected ILD or non-infectious pneumonia at screening that cannot be excluded by
imaging examinations;
15. Documented history of severe dry eye syndrome, severe meibomian gland disease and/or
blepharitis, or severe corneal diseases that may impede/delay corneal healing;
16. Clinically severe lung damage caused by concurrent pulmonary diseases, including but
not limited to any underlying lung diseases (such as severe asthma, severe chronic
obstructive pulmonary disease, restrictive lung disease within 3 months before the
first dose) or any autoimmune, connective tissue, or inflammatory diseases that may
involve the lungs (i.e., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis,
etc.), or previous pneumonectomy;
17. Subjects with active chronic inflammatory bowel disease, gastrointestinal
obstruction, severe ulcer, gastrointestinal perforation, abdominal abscess, or acute
gastrointestinal bleeding;
18. Proteinuria, evidenced by protein > 1.0 gram in urine test strip or 24-hour urine
collection. All patients with protein ≥ 2+ in baseline urine test strip analysis
must undergo 24-hour urine collection, and the protein in 24 hours must be proven to
be ≤ 1 g;
19. Toxicity from previous anti-tumor treatment has not recovered to ≤ grade 1 (assessed
based on NCI CTCAE v5.0) or the level specified in the inclusion/exclusion criteria
