| Eligibility |
Inclusion Criteria:
1. Age from 18 to 75 years old.
2. Histology or cytology is confirmed to be NSCLC, imaging confirmed to be advanced NSCLC
with brain metastasis (including relapsed or newly diagnosed advanced patients after
previous surgical treatment; according to AJCC eighth edition lung cancer staging
standards).
3. Tumor tissue samples or blood samples are confirmed to be EGFR sensitive mutations
(including exon 19 deletion or L858R, both alone or coexist with other EGFR
mutations). Tumor tissue is the first choice for examination; if the tumor tissue is
not accessible or the patient cannot accept a tissue biopsy, a blood sample can be
sent.
4. Have not received any systemic treatment. For patients who have received local
treatment, the lesion within the scope of the local treatment cannot be used as the
target lesion unless the lesion has progressed.
5. Patients are required to have a measurable extracranial lesion that has not undergone
local treatment or has shown progression after local therapy, with a baseline longest
diameter of at least 10 mm (or 15 mm for lymph nodes), and at least one intracranial
lesion with a baseline longest diameter of at least 5 mm.
6. The brain condition is stable for at least 2 weeks before the study drug treatment,
without any systemic (oral or parenteral) corticosteroid or anticonvulsant drug
treatment. Non-absorbable corticosteroids can be used locally and inhaled according to
the indications.
7. The Eastern Cooperative Oncology Group (ECOG) physical status score is 0 or 1, and has
not deteriorated at least 2 weeks before the study drug treatment, and the expected
survival period is not less than 12 weeks.
8. Female patients of childbearing age are willing to take appropriate contraceptive
measures and should not breastfeed from signing the informed consent to 6 months after
the last study drug treatment; male patients are willing to take appropriate
contraceptive measures from signing the informed consent to 6 months after the last
study drug treatment Use barrier contraception (ie condoms).
9. Female patients of childbearing age must have a negative serum or urine HCG test
within 7 days before enrollment in the study, and they must be non-lactating.
10. The subject voluntarily participated and signed an informed consent form in writing.
Exclusion Criteria:
1. Treatment with any of the following:
1. Previously received EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment (such as
erlotinib, gefitinib, icotinib, afatinib, osimertinib, and almonertinib, etc.) );
2. Within 4 weeks before the first administration of the study drug, the patient has
undergone major surgery (such as craniotomy, thoracotomy, or laparotomy, etc.),
or underwent minor traumatic surgery (biopsy, bronchoscopy, and Thoracic
drainage). The definition of major surgery refers to the level 3 and level 4
surgery specified in the "Administrative Measures for the Clinical Application of
Medical Technology" in Appendix H, which was implemented on November 1, 2018;
3. Except for patients who have received local radiotherapy (palliative bone
radiotherapy for non-target lesions) within 2 weeks before the first
administration of the study drug; within 4 weeks before the first administration
of the study drug, more than 30% of the bone marrow has been irradiated
(calculated area of the bone marrow) See Annex I), or received extensive
radiotherapy; received whole brain radiotherapy due to this disease before
enrollment;
4. Recurrence within 6 months after adjuvant or neoadjuvant treatment for early lung
cancer; if there is both neoadjuvant therapy and adjuvant therapy, the adjuvant
treatment time will be calculated;
5. Within 14 days before the first administration of the research drug, Chinese
medicines and preparations with anti-tumor therapy or anti-tumor adjuvant therapy
have been used (see Appendix E for the list of drugs);
6. There is pleural effusion/peritoneal effusion that requires clinical intervention
(patients who do not need to drain the effusion or who are stable for 2 weeks or
more can be included in the group); there is pericardial effusion (a small amount
of pericardium that is stable for 2 weeks or more) Fluid effusion is allowed to
enter the group). If anti-tumor drugs have been used locally (such as chest
cavity perfusion) during drainage, at least 5 drug half-lives or 21 days
(whichever is shorter) must be eluted before the first administration of the
study treatment before they can be included in the group;
7. Within 7 days before the first administration of the study drug, have used CYP3A4
strong inhibitors, strong inducers, or narrow therapeutic window drugs with
sensitive substrates, or need to continue to receive these drugs during the study
period (see Appendix E for the list of drugs);
8. Are receiving drugs that are known to prolong the QT interval or may cause
torsades de pointes, or need to continue to receive these drugs during the study
period (see Appendix E for the drug list and washout time);
9. The 5 half-lives of the study drug that participates in other clinical trials as
a subject or is still in other clinical trials within 4 weeks before the first
administration of the study drug, whichever is longer (except for screening
failure).
2. Mixed SCLC and mixed NSCLC, large cell neuroendocrine carcinoma and sarcomatoid
carcinoma confirmed by histology or cytology.
3. At the beginning of the study drug treatment, those with unresolved residual toxicity
from previous anti-tumor therapy greater than CTCAE level 1, except for hair loss and
level 2 neurotoxicity caused by previous anti-tumor. In the past, intracranial
hemorrhage unrelated to the tumor occurred.
4. History of other primary malignant tumors, except for the following:
1. Malignant tumors that have been cured, have no activity for =5 years and have a
very low risk of recurrence before being selected for the study;
2. Non-melanoma skin cancer or malignant freckle-like nevus that has been adequately
treated and has no evidence of disease recurrence;
3. Carcinoma in situ with adequate treatment and no evidence of disease recurrence.
5. Diagnosis of meningeal metastasis through clinical symptoms or imaging or
cerebrospinal fluid, or brain parenchymal metastasis combined with meningeal
metastasis.
6. Patients who are allergic to MRI contrast agent gadolinium or who cannot tolerate MRI
examinations (such as pacemakers, metals in the body, etc.).
7. As judged by the investigator, there are any serious or poorly controlled systemic
diseases, such as poorly controlled hypertension, active bleeding-prone constitution,
or active infection. No need to check for chronic diseases.
8. Clinically serious abnormal gastrointestinal function, which may affect the intake,
transport or absorption of drugs, such as inability to take drugs orally,
uncontrollable nausea or vomiting, history of extensive gastrointestinal resection,
uncured recurrent diarrhea, atrophy Gastritis, uncured gastric diseases that require
proton pump inhibitors for a long time, Crohn's disease, ulcerative colitis, etc.
9. Hepatic encephalopathy, hepatorenal syndrome or cirrhosis.
10. Meet any of the following cardiac examination results:
1. The average value of QT interval (QTcF) corrected by Fridericia's formula
obtained from 3 ECG examinations at rest> 470 msec;
2. Resting ECG suggests that there are various clinically significant rhythms,
conduction or ECG morphological abnormalities that are judged by the investigator
(such as complete left bundle branch block, 3 degree atrioventricular block, 2
degree atrium Ventricular block and PR interval> 250 msec, etc.);
3. There are any factors that increase the risk of QTc prolongation or arrhythmia
events, such as heart failure, hypokalemia, congenital long QT syndrome, family
history of long QT syndrome, or unexplained sudden death or prolonged QT of
immediate family members under 40 Any concomitant drugs in the interval;
4. Left ventricular ejection fraction (LVEF) <50%.
11. Insufficient bone marrow reserve or organ function, reaching any one of the following
laboratory limits (no corrective treatment within 1 week before laboratory examination
of blood draw):
1. Absolute neutrophil count <1.5×109 / L;
2. Platelet count <100×109 / L;
3. Hemoglobin <90 g/L (<9 g/dL);
4. If there is no clear liver metastasis, alanine aminotransferase> 2.5 times the
upper limit of normal (ULN); if there is liver metastasis, alanine
aminotransferase> 5×ULN;
5. If there is no clear liver metastasis, aspartate aminotransferase> 2.5×ULN; if
there is liver metastasis, aspartate aminotransferase> 5×ULN;
6. If there is no clear liver metastasis, total bilirubin> 1.5×ULN; or Gilbert
syndrome (unconjugated hyperbilirubinemia) or liver metastasis, total bilirubin>
3×ULN;
7. Creatinine>1.5×ULN and creatinine clearance rate<50 mL/min (calculated by
Cockcroft-Gault formula); Only when creatinine>1.5×ULN, creatinine clearance rate
needs to be confirmed;
8. Serum albumin (ALB) <28 g/L;
12. Active fungal, bacterial and/or viral infections requiring systemic treatment.
13. Female subjects who are pregnant, lactating, or planning to become pregnant during the
study period.
14. A history of interstitial lung disease, a history of drug-induced interstitial lung
disease, a history of radiation pneumonitis requiring steroid therapy, or any evidence
of clinically active interstitial lung disease.
15. Have a history of hypersensitivity to any active or inactive ingredients of
almonertinib or to drugs with similar chemical structure to almonertinib or the same
class of almonertinib.
16. Any serious or uncontrolled eye disease (especially severe dry eye syndrome, dry
keratoconjunctivitis, severe exposure keratitis or other diseases that may increase
epithelial damage) may increase the safety of the patient by the doctor's judgment
Sexual risk; or those with eye abnormalities that require surgery or are expected to
require surgical treatment during the study period.
17. Patients who may have poor compliance with the procedures and requirements of the
study as judged by the investigator, such as patients who have a clear history of
neurological or mental disorders (including epilepsy or dementia), and currently
suffer from mental disorders.
18. The investigator judges that there are any patients with conditions that endanger the
safety of the patient or interfere with the evaluation of the study.
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