Phase II Umbrella Study Directed by Next Generation Sequencing

Exclusion Criteria

• •1. Active hepatitis (HBsAg positive and HBV copy number in upper limit of normal)
• •2. Previous or current active interstitial lung disease (ILD)
• •3. Patients known to be HIV positive or with other acquired, congenital immunodeficiency diseases, or with a medical history of organ transplantation.
• •4. Major surgery ≤ 2 weeks prior to study entry.
• •5. Any other malignancies within the last 5 years before study enrollment, except for un completely resected basal cell carcinoma, in situ bladder cancer, cervical carcinoma in situ.
• •6. Patients previously treated with the investigational drugs or known to be allergic to ingredients or excipients of the investigational drugs.
• •7. Pregnant or lactating women.
• •8. Patients with swallowing dysfunction, active gastrointestinal disease or other diseases that significantly affect the absorption, distribution, metabolism and excretion of oral drugs. The patients who have had subtotal gastrectomy before. (this standard is applicable to the arms with oral drugs only)
• •9. Body temperature above 38 ℃ in the past week, or there was active infection with clinical significance. Active tuberculosis;
• •10. Evidence of serious or uncontrollable systemic diseases (such as severe mental, neurological, epilepsy or dementia, unstable or uncompensated respiratory, cardiovascular, liver or kidney diseases, uncontrolled hypertension \[higher than CTCAE Level 3 hypertension after drug treatment\]);
• •11. Patients with bleeding tendency or taking anticoagulants ;
• •12. There are significant clinical abnormalities in rhythm, conduction or morphology of resting ECG, such as complete left bundle branch block, heart block above degree II, clinically significant ventricular arrhythmia or atrial fibrillation, unstable angina, congestive heart failure, chronic heart failure with NYHA grade ≥ 2.
• •13. Myocardial infarction, coronary / peripheral artery bypass or cerebrovascular accident occurred within 3 months.
• •14. QTc of 12 lead ECG was ≥ 450 ms in male and ≥ 470 ms in female;
• •15. Diagnosed with another malignant disease in the past five years besides NSCLC.
• •16. More than 30% of the bone marrow had received radiotherapy within 4 weeks before treatment.
• •17. Any drugs known to extend QT interval were being used within 2 weeks prior to first administration.
• •18. Strong CYP3A4 inhibitor/inductionor or CYP3A4 substrate were used within 2 weeks, including but not limited to azanavir, clarithromycin, inddenavir, itraconazole, ketoconazole, nefazodone, nefinavir, ritonavir, xaquinavir, talicamycin, acesodamycin, voriconazole, carbamazepine, phenobarbital, phenytoin, rifampin, rifampin, Hypericum perforatum, dihydroergotamine, ergotamine, pimozite, astemizole, cisapride and terfenadine.
• •19. Strong P-gp inhibitor was used within 2 weeks (including but not limited to verapamil, cyclosporine A and right verapamil).
• •20. Other potential risks that are not suitable for the study.