| Eligibility |
Inclusion Criteria:
- (1) Fully understand the purpose of the experiment, the investigator judges that he
can abide by the experiment protocol, and voluntarily sign a written informed consent.
(2) The age at the time of signing the informed consent is =18 years old, regardless
of gender.
(3) Patients with non-squamous non-small cell lung cancer (NSCLC) diagnosed by
histology/cytology.
(4) According to the TNM staging of UICC 8th edition, it is determined as ?B (not
suitable for surgery or radiotherapy)-IV stage NSCLC.
(5) The patient has EGFR exon 19 deletion (19del) or 21 exon [L858R] mutation
confirmed by the central laboratory (only tissue samples are accepted), and it is
suitable for first-line treatment of EGFR-TKI.
(6) Have not received any systemic treatment for non-small cell lung cancer in the
past, and have not received any EGFR-TKI drug treatment. If the subject has received
adjuvant/neo-adjuvant therapy and then relapses, but the end of adjuvant/neo-adjuvant
therapy is more than 6 months after the first dose of this study, the subject can also
be included in the group.
(7) There is at least one measurable lesion based on RECISTv1.1. (8) The ECOG score is
0~1. (9) The functions of major organs and bone marrow are basically normal. It is
required that no blood transfusion or hematopoietic stimulating factors have been used
within 14 days before screening. The laboratory test results are the results within 7
days before the start of treatment:
?Cagulation function INR=1.5×ULN, aPTT=1.5×ULN (if the subject is receiving
anticoagulant therapy Treatment, as long as the aPTT is within the expected treatment
range of anticoagulant drugs);
?The subject's liver and kidney function meets the following conditions: total
bilirubin=1.5×ULN, ALT and AST=2.5×ULN, if the liver is invaded by tumor, AST and
ALT=5×ULN; endogenous creatinine clearance =60mL/min (Cockcroft-Gault formula); urine
protein is 0 or 1, or urine protein quantitative <1g/24h ;
?The blood routine meets: neutrophil count =1.5×109/L, platelet =100×109/L, hemoglobin
=9g/dL.
(10) Adverse reactions caused by previous local treatments, surgery or other
anti-cancer treatments have recovered to = CTCAE level 1 (except for hair loss).
(11) The life expectancy of the patient is> 12 weeks. (12) Take effective
contraceptive measures throughout the study period until 12 weeks after the last
medication.
Exclusion Criteria:
1. The patient is positive for EGFR T790M mutation, positive for ALK fusion, or has any
other co-mutations (a report is required if co-mutation has been tested, and testing
is not mandatory if it has not been tested).
2. Suffered from other malignant tumors other than NSCLC within 5 years or at the same
time (except cured skin basal cell carcinoma, prostate carcinoma in situ and cervical
carcinoma in situ).
3. Symptomatic central nervous system (CNS) metastasis.
4. Received major surgery, needle biopsy or subcutaneous venous access device placement
within 7 days before the start of study treatment. Any post-operative bleeding or
wound complications occurred within 2 months before the start of study treatment.
5. Before the start of the study treatment, received radiotherapy in the bone marrow area
=25% of the radiotherapy area, received palliative chest radiotherapy within 28 days,
or received radiotherapy for local relief or prevention of symptoms (such as pain,
bleeding or obstruction) within 7 days.
6. Idiopathic pulmonary fibrosis confirmed by CT/X-ray; X-ray confirmed or had acute lung
injury,Pneumoconiosis; have or have had radiation pneumonia or drug-induced pneumonia;
clinically active interstitial lung disease (chronic, stable,Except for asymptomatic
patients with imaging changes); imaging evidence shows lung cavities.
7. Pleural effusion, pericardial effusion, or ascites and need to be drained every other
week or more frequently.
8. Superior vena cava syndrome.
9. Patients with any serious and/or uncontrollable diseases, including:
- Major cardiovascular disease (NYHA grade II-IV heart disease, myocardial
infarction or under study Stroke occurred within 3 months before the start),
unstable angina pectoris, unstable arrhythmia, congenital QT prolonged syndrome,
or QTc interval corrected for the screening period> 500ms ( Bazetts formula: QTcB
= QT/RR0.5); ?Past hypertensive crisis or history of hypertensive encephalopathy,
hypertension not controlled by drugs (defined as systolic blood pressure =150mmHg
and/or diastolic blood pressure >100mmHg);
- Severe infections that are active or uncontrolled, such as nosocomial
infections, bacteremia, severe lung infections, etc.; ?Patients with severe
immunodeficiency (except those related to corticosteroid use), including
those who are known to be HIV-positive; ? Liver damage: Child-Pugh grade B
(or worse) with severe liver cirrhosis; liver cirrhosis with a history of
hepatic encephalopathy; clinically significant ascites caused by liver
cirrhosis, which requires diuretic and/or puncture treatment; yes History of
hepatorenal syndrome.
10. Evidence of major coagulopathy or other obvious bleeding tendency:
- Bleeding incidents caused by esophageal and/or gastric varices occurred within 6
months before the start of the study treatment;
- Hemoptysis occurred within 1 month before the start of study treatment (>2.5
mL bright red blood each time);
- Thrombosis or embolism events, major vascular diseases (such as aortic
aneurysms that require surgical repair) occurred within 6 months before
the start of the study treatment; ?Current or recent (within 10 days
before the start of the study treatment) anticoagulant therapy for
therapeutic purposes (except for low molecular weight heparin therapy);
?Current or recent (within 10 days before the start of the study
treatment) use aspirin (>325 mg/d) or ticlopidine, clopidogrel,
cilostazol for treatment; ?Patients with imaging evidence that there
are large blood vessels invaded or wrapped, and there is a significant
risk of bleeding.
11. Abdominal or tracheoesophageal fistula, gastrointestinal perforation, or
intra-abdominal abscess within 6 months before the start of study treatment.
12. Severe, non-healing or dehiscence wounds, active ulcers or untreated fractures.
13. There are factors that significantly affect the absorption of oral drugs, such as
inability to swallow, chronic diarrhea, and intestinal obstruction.
14. Being treated with CYP3A4 inducers (such as rifampicin or phenytoin) or strong
inhibitors (such as itraconazole or ketoconazole).
15. Proton pump inhibitors (such as esomeprazole magnesium or omeprazole) need to be used
daily.
16. Any known serious ocular surface disease.
17. Those who are known to be allergic to any component of the therapeutic drug, or have a
history of allergy to monoclonal antibody therapy.
18. Previously received allogeneic stem cell or solid organ transplantation.
19. The research treatment was conducted within 4 weeks before the start of the research
treatment.
20. Are pregnant or breastfeeding.
21. For any other disease, metabolic dysfunction, physical examination or clinical
laboratory examination to find contraindications to the study drug, the investigator's
judgment may affect the interpretation of the results, or may put the patient at a
high risk of treatment complications.
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