1. Age 18-75 years old (calculated from the time when the subject signed the informed
consent), both male and female.
2. Confirmed pathology of EGFR mutation positive（exon 19 deletion, L858R, T790M）NSCLC
with brain metastases on enhanced MRI.
3. Subjects had not previously received chemotherapy, EGFR-TKI, biologic or
immunotherapy, or other experimental therapy as first-line treatment for advanced
4. According to RECIST 1.1 criteria, subjects must have a measurable target lesion
(maximum diameter under MRI/CT ≥10mm, short diameter of lymph node ≥15mm) that has
been examined by CT or MRI.Tumor imaging evaluation was performed within 28 days prior
to initial treatment.
5. ECOG PS score: 0-1 points.
6. Must be able to swallow tablets，and expected survival ≥3 months.
7. Clinical diagnosis of Alzheimer's patients who can be treated with radiation therapy.
8. All screening laboratory tests are performed according to protocol and need to be
performed within 14 days prior to the first dose.The values of laboratory tests
performed by screening must meet the following criteria:
1. Routine blood examination :(no blood transfusion, no G-CSF, no drug correction
within 14 days before screening)
- - Hemoglobin (Hb) ≥90 g/L;
- Absolute neutrophil count (ANC) ≥1.5×109/L;
- Platelet count (PLT) ≥100×109/L;
- White blood cell count (WBC) ≥4.0×109/L and ≤15×109/L;
Biochemical test :(no blood transfusion or albumin within 14 days prior to
- - AST and ALT ≤1.5×ULN (such as cancer that has spread to the liver, ≤5×ULN);
- ALP≤2.5×ULN (such as tumor bone metastases, ≤5×ULN);
- - ALB≥30 g/L;
- Cr≤1.5×ULN, while creatinine clearance (CrCL)≥60 mL/min (Cockcroft - Gault
- APTT≤1.5×ULN, at the same time of INR or PT≤1.5×ULN (without anticoagulation
9. Women of childbearing age must have a serum pregnancy test within 3 days prior to the
first dose and the results are negative.Women of reproductive age subjects and male
subjects whose partners are women of reproductive age must agree to use barrier
contraception (i.e., condoms) during the study period and for 180 days after the last
administration of the study drug.
10. Volunteered to participate in clinical studies and signed informed consent.
1. Exclusion criteria for target diseases:
1. Subjects who had previously received anti-EGFR-TKI therapy.
2. Patients with neuromeningeal disease but no intracranial metastases confirmed by
MRI and/or CSF malignancy.
3. Previous radiotherapy for CNS metastases, including measurable or unmeasurable
sites of the disease for efficacy assessment.
4. Patients who had undergone a major surgical procedure (other than placement of
vascular access or CNS shunt) or had a major traumatic injury or were expected to
require major surgery during the study period within 4 weeks prior to initial
5. Subject who can be surgically excised or treated with radical radiotherapy.
2. History and complications:
1. The patient is using (or cannot be discontinued for at least 1 week prior to the
first dosing of the investigational treatment) some drug or herbal supplement
known to be a strong depressant or inducer of CYP3A4/5 (Appendix 8).
2. Excluding uncontrollable nausea and vomiting, chronic gastrointestinal disease,
prior gastrectomy or other surgery, may affect the full absorption of the study
3. exclude the presence of any serious or uncontrolled systemic disease or
- - Uncontrolled high blood pressure, diabetes, thyroid disease;
- Severe heart, lung or kidney disease;
- Active bleeding constitution;
- Any bacterial, viral, fungal or other active infection that the Investigator
considers to pose a serious risk to the patient;
- Active hepatitis (HBsAg positive or HBcAb positive, HBV DNA positive), or
HCV antibody positive or HIV positive.
4. Patients with unstable symptomatic metastases: Any unstable and symptomatic CNS
or distant metastases that were not controlled by previous surgery, radiotherapy,
or corticosteroid treatment within 2 weeks prior to the initial study
treatment.Corticosteroids were used before treatment for CNS symptoms, but the
symptoms were controllable after treatment, and corticosteroids were used during
5. Exclude subjects who are participating in other clinical studies or whose first
administration has been less than 3 weeks (or 5 half-lives of the investigational
drug) since the end of the previous clinical study (last dosing).
6. Excluding subjects who expected to require any other form of antitumor therapy
(including maintenance therapy with other NSCLC drugs, and/or surgical resection)
during the study.
7. excluded subjects with high suspicion of interstitial pneumonia; Or subjects that
may interfere with the detection or management of suspected drug-related
pulmonary toxicity;Or other moderate to severe lung diseases that seriously
affect lung function.
8. Subjects with other active malignancies requiring concurrent treatment were
9. Subjects with a previous history of malignancy were excluded unless they had
achieved a complete response at least 5 years prior to screening and did not
require or are not expected to require additional treatment during the study
period for basal cell carcinoma of the skin, superficial bladder carcinoma,
squamous cell carcinoma of the skin, or cervical carcinoma in situ.Rule out with
Ⅱ magnitude myocardial ischemia and myocardial infarction, arrhythmia of the
subjects of poor control.
10. Ruled out according to the NYHA standard Ⅲ ~ Ⅳ level cardiac insufficiency or
heart colour to exceed examination: LVEF, left ventricular ejection fraction <
50% of the subjects.
11. Patients with significant hemoptysis or hemoptysis of half a teaspoon (2.5ml) or
more per day within 1 month before randomization.
12. Patients with bleeding symptoms of significant clinical significance or with
definite bleeding tendency, such as gastrointestinal bleeding, hemorrhagic
gastric ulcer, or vasculitis, occurred within 1 month prior to randomization.
13. Artery/venous thrombosis events occurred in the first 3 months at random, such as
cerebrovascular accidents (including transient ischemic attack, cerebral
hemorrhage, cerebral infarction), deep venous thrombosis and pulmonary embolism,
14. Subjects with active tuberculosis (TB) were excluded.In subjects suspected of
active TB, chest X-rays and sputum should be examined, and clinical signs and
symptoms should be excluded.Subjects with a history of active tuberculosis
infection within the previous 1 year were screened, even if they had been
treated. Subjects with a history of active TB infection more than 1 year ago
should also be excluded unless the course and type of anti-TB treatment
previously used is demonstrated to be appropriate.
15. Excluding subjects who were preparing for or had previously received tissue/organ
16. Subjects who received or will receive live vaccine within 30 days prior to the
first dose were excluded.
17. Inclusion of subjects with uncontrolled tumor-related pain is not
recommended.Subjects requiring pain medication must have a stable pain control
regimen;Symptomatic lesions suitable for palliative radiotherapy (such as bone
metastases or nerve invasion metastases) should be completed at least 2 weeks
before inclusion; Asymptomatic metastatic foci whose further growth may result in
dysfunction or intractable pain (e.g. epidural metastases that do not show spinal
cord compression) should be considered for local-regional treatment before
randomization, if appropriate.
3. Physical examination and laboratory examination. 1. A known history of positive human immunodeficiency virus (HIV) tests or a known
history of acquired immunodeficiency syndrome (AIDS).
2. Untreated active hepatitis:
- - Hepatitis B: HBV surface antigen (HBV sAg) positive and HBV DNA detection
value is higher than the upper limit of normal value;
- Hepatitis C: Hepatitis C virus antibody (HCV Ab) positive, HCV RNA positive,
and abnormal liver function;
- Complicated with hepatitis B and C co-infection.
3. Exclude subjects with uncontrolled pleural effusion, pericardial effusion, or
ascites requiring repeated drainage.
4. Allergic reactions and adverse drug reactions:Study drugs with CYP3A4 inhibition
agents, inducers, or drugs with a narrow therapeutic window that are CYP3A4-sensitive
substrates were used within 7 days before the first administration.
5. Patients receiving concurrent chemotherapy were excluded.
6. Excludes subjects with mental illness, alcoholism, inability to quit smoking, drug or
7. At the discretion of the Investigator, exclude subjects with history or current
evidence of any disease, treatment or laboratory anomaly that may confuse study
results, interfere with subjects' participation in the study procedure, or is not in
the best interest of subjects' participation in the study.