| Eligibility |
Inclusion Criteria:
Subjects who must meet all the following criteria should be selected:
1. Agree to participate in this trial and sign written informed consent form.
2. Male or female, age between 18 and 70 years.
3. Expected survival time = 3 months and able to be followed-up.
4. Stage IIIB/IIIC/IV non-squamous NSCLC patients without previous systemic therapy
(according to AJCC8th) or patients with stage IIIB/IIIC/IV non-squamous NSCLC who have
relapsed after surgery (if adjuvant therapy was administered, more than 6 months of
drug discontinuation is required).
5. The tumor harbors epidermal growth factor receptor (EGFR) mutations(include 19del,
L858R, T790M, G719X, L861Q, S768I, 20 A763-Y764ins), and at least concurrent with TP53
6. Patients can not receive concurrent chemoradiothrapy after multidisciplinary
consultation and discussion.
7. At least one measurable tumor indicator along with a lesion with a maximum diameter of
= 1 cm (diagnosed by imaging, e.g., CT, MRI, ECT).
8. ECOG PS 0-1 within 7 days before enrollment.
9. Within 14 days prior to the start of treatment, laboratory results of routine blood,
liver and kidney function and hormone levels meet the following criteria: white blood
cell(WBC) =3.5× 109/L, platelets (PLT) = 80 × 109/L, neutrophils (ANC) = 1.5 × 109/L,
hemoglobin (HGB) = 80 g/L, aspartate aminotransferase (AST) = 2.5 × upper limit of
normal (ULN) (= 5 × ULN for liver metastases), alanine aminotransferase (ALT) = 2.5 ×
ULN (= 5 × ULN for liver metastases), total bilirubin (TIBC) = 1.5 × ULN, and alanine
aminotransferase (ALT) = 1.5 × ULN. × ULN), alanine aminotransferase (ALT) = 2.5 × ULN
(= 5 × ULN for liver metastases), total bilirubin (TIBC) = 1.5 × ULN, serum creatinine
(CR) = 1.25 × ULN; cortisol and thyroid function are in the normal range.
10. Toxic effects of prior chemotherapy have resolved to grade 1 or less (except
alopecia). Subjects must have recovered from toxicity or complications of these
interventions if they have received major surgical treatment or > 30Gy of radiation
therapy, i.e., they are still eligible for enrollment after 6 months.
Exclusion Criteria:
Subjects who meet any of the following criteria could not participate in this study:
1. non-squamous NSCLC just harbors EGFR mutations
2. Prior treatment with first,second and 3rd EGFR-TKI.
3. Received bevacizumab and/or pemetrexed within 6 months prior to the first dose of
study drug.
4. Prior treatment with PD-1/PD-L1 antibodies within 3 months prior to the first dose of
study drug.
5. Received anti-tumor monoclonal antibody (mAb), chemotherapy, targeted small molecule
therapy, or major surgical procedure within 1 month prior to the first use of study
drug; received chest radiation therapy greater than 30 Gy within 6 months prior to the
first use of study drug; received chest radiation therapy at 30 Gy or less within 1
month prior to the first use of study drug.
6. Participating or have participated in investigational drug therapy within 4 weeks
prior to the first dose of the trial.
7. Other malignant tumors with disease progression or requiring aggressive treatment
within 5 years of enrollment. Exceptions included early-stage tumors (carcinoma in
situ or stage I tumors) that received radical treatment, basal cell carcinoma of the
skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or
carcinoma in situ of the breast that received potentially radical treatment.
8. Having congenital or acquired immune deficiency (e.g., HIV-infected patients), active
hepatitis B (HBV-DNA =10^3 copies/ml), or hepatitis C (positive for hepatitis C
antibodies and HCV-RNA above the lower limit of detection for the assay).
9. Patients who have received live vaccine within 4 weeks prior to the first
administration of study drug are permitted to receive inactivated viral.
10. Patients with known active central nervous system (CNS) metastases and/or cancerous
meningitis. Subjects who have had treatment for brain metastases may also participate
in this study provided that the subject is stable (no evidence of progression for at
least 4 weeks and all neurological symptoms have returned to baseline levels as
determined by MRI prior to the first dose), has no evidence of new or expanding brain
metastases, and has not used hormone therapy for at least 3 days prior to study
dosing.
11. Bleeding tendency, high bleeding risk, or coagulopathy with a history of thrombotic
disease within 6 months and/or hemoptysis within 3 months; being treated with full
doses of oral and/or parenteral anticoagulants and thrombolytics (prophylactic
anticoagulation is allowed); having used aspirin or other non-steroidal
anti-inflammatory drugs that inhibit platelet function within 10 days; and CT/MRI
imaging showing tumor encapsulation or invasion of the lumen of large blood vessels.
12. Poorly controlled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg) and
patients with prior hypertensive crisis and hypertensive encephalopathy; severe
cerebrovascular disease.
13. Non-healing wounds, peptic ulcers in active phase, tracheo-esophageal fistulas,
gastrointestinal perforations and intra-abdominal abscesses within 6 months.
14. Have an active infection that requires systemic treatment via Intravenous injection.
15. Have mental illness or other condition, such as uncontrolled heart or lung disease,
diabetes mellitus, etc., that prevents cooperation with study treatment and monitoring
requirements.
16. Known allergy to any of the components of the study drug.
17. Patients who are regular users of any drug (including "recreational" use) or have
recent history (within 1 year) of substance abuse (including alcohol) when signing the
informed consent form.
18. Pregnancy or breast feeding.
19. Poor compliance and inability to cooperate with the clinical study.
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