This phase II, umbrella trial study directed by next generation sequencing (NGS) works in
Chinese patients with advanced stage NSCLC who never received any anti-tumor treatment. The
purpose of this study is to evaluate efficacy of targeted therapies or immunotherapy to NSCLC
patients whose tumor harbors a genomic variant known to be a drug target or to predict
sensitivity to a drug.
1. Histologically or cytologically confirmed, unresectable stage IIIB or stage IV NSCLC
2. Patients who have never received any anticancer treatment regimen Note: Patients that
have received adjuvant or neoadjuvant chemotherapy and developed metastatic disease
after 12 months from the end of that therapy would be eligible for enrollment.
3. Measurable disease according to RECIST v.1.1 (Irradiated lesions are not considered
measurable unless they have clearly progressed since radiotherapy)
4. With or without brain or leptomeningeal metastasis (BM/LM). For patients with symptoms
of BM/LM, no need for local therapy should be confirmed by investigator and no
dramatic decline of performance status in 2 weeks.
5. ECOG performance status ≤ 2
6. Expected survival > 12 weeks
7. Patients must be suitable and willing to undergo mandatory tumor biopsy according to
treating institution's guidelines and requirements for such procedure if there is no
archival biopsy available.
8. Provision of signed and dated written informed consent by the patient or legally
acceptable representative prior to any study-specific procedures.
9. Palliative radiotherapy was allowed before enrollment, and radiotherapy-related
toxicity grade should no more than 1 (ctcae4.03).
10. No anti-tumor Chinese medicine has been used in the past, or has been used for no more
than 3 doses, and stopped for more than 2 weeks before enrollment.
11. Absolute neutrophil count (ANC) ≥ 1.5x10^9/L without the use of growth factor in the
past 14 days. Platelets ≥ 90 × 10^9/L without blood transfusion in the past 14 days.
Hemoglobin > 9g/dL.
12. Negative pregnancy test (only for women with pregnancy possibility). No possibility of
pregnancy defined as at least one year after menopause, or having undergone surgical
sterilization or hysterectomy. All patients (male or female) agreed to take
contraceptive measures during the treatment and within 8 weeks after the treatment.
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
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
17. Any drugs known to extend QT interval were being used within 2 weeks prior to first
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
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.