| Eligibility |
Inclusion Criteria:
1.18 = age and above. 2. Histology or cytology is confirmed as NSCLC, imaging confirmed as
advanced NSCLC with brain metastasis (including relapsed or newly diagnosed advanced
patients after previous surgical treatment; according to AJCC eighth edition lung cancer
staging standard).
3. Progressed after receiving first or second generation EGFR-TKI treatment, T790M
positive.
4. According to RECIST1.1, the patient has at least 1 intracranial target lesion and 1
extracranial target lesion. The requirements for target lesions are: measurable lesions
that have not undergone local treatment such as irradiation or have clearly progressed
after local treatment, with the longest diameter at baseline =10 mm (if it is a lymph node,
the maximum short diameter is required to be =15 mm).
5. 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.
6. The Eastern Cooperative Oncology Group (ECOG) physical status score is 0 or 1, and there
is no deterioration at least 2 weeks before the study drug treatment, and the expected
survival period is not less than 12 weeks.
7. Female patients of childbearing age are willing to take appropriate contraceptive
measures from signing the informed consent to 6 months after the last treatment with the
study drug and should not breastfeed; male patients are willing from signing the informed
consent to 6 months after the last treatment with the study drug Use barrier contraception
(ie condoms).
8. 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.
9.The subjects themselves participated voluntarily and signed a written informed consent
form.
Exclusion Criteria:
1. Have received any of the following treatments:
1. 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;
2. Except for patients who have received local radiotherapy (palliative radiotherapy
for bone in 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,
they have received more than 30% bone marrow irradiation (calculated area of bone
marrow) See Annex I), or received extensive radiotherapy; received whole brain
radiotherapy due to this disease before enrollment;
3. 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;
4. 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 after drainage can be included); 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 being included in the group;
5. Within 7 days before the first administration of the study drug, have used CYP3A4
strong inhibitors, strong inducers or drugs with a narrow therapeutic window of
sensitive substrates, or need to continue to receive these drugs during the study
period (see Appendix E for the list of drugs);
6. 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);
7. Within 4 weeks before the first administration of the study drug, the five
half-lives of the study drug as a subject participating in other clinical trials
or still in other clinical trials, 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, there is a residual toxicity of the
previous anti-tumor treatment that is greater than CTCAE level 1 that has not been
relieved, except for hair loss and level 2 neurotoxicity caused by the 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 been inactive 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 by 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. Any serious or poorly controlled systemic disease, as determined by the investigator,
such as poorly controlled hypertension, active bleeding susceptibility, or active
infection. There is no need to screen 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, 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 QT interval (QTcF) corrected by Fridericia's formula obtained from 3
ECG examinations in the resting state> 470 msec;
2. Resting ECG prompts the existence of various clinically significant rhythms,
conduction or ECG morphological abnormalities 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 the age of 40 Any concomitant drugs in the
interval;
4. Left ventricular ejection fraction (LVEF) <50%.
11. Insufficient bone marrow reserve or organ function, reaching any of the following
laboratory limits (no corrective treatment within 1 week before laboratory examination
of blood):
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 transfer, aspartate aminotransferase> 2.5×ULN; if
there is liver transfer, 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. Infections in which pathogenic bacteria that are currently producing symptoms or
diseases that require systemic treatment are rapidly multiplying, that is, active
infections. Including active fungal, bacterial and/or viral infections (such as HBV,
HIV, etc.).
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 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 patients by the doctor's judgment Sexual
risk.
17. Patients who may have poor compliance with the research procedures and requirements,
such as patients who have a clear history of neurological or psychiatric disorders
(including epilepsy or dementia), and currently suffer from mental disorders, etc., as
judged by the investigator.
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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