1. Subjects must meet all the following criteria to be enrolled in this study: subjects
will voluntarily participate and sign a written informed consent.
2. Male or female, aged at least 18 years.
3. ECOG performance status of 0 to 2. Life expectancy of at least 12 weeks.
4. Patients had histologically or cytologically confirmed locally advanced or metastatic
pancreatic adenocarcinoma not amenable to curative surgery or radiotherapy.
5. The tumour harbours one of the 2 common EGFR mutations known to be associated with
EGFR-TKI sensitivity (Ex19del, L858R).
6. Tumour tissue sample in a quantity sufficient to allow for central analysis of EGFR
7. Patients must be treatment-naïve for locally advanced or metastatic NSCLC and eligible
to receive first-line treatment with gefitinib or erlotinib as selected by the
participating centre. Prior adjuvant and neo-adjuvant therapy is permitted
(chemotherapy, radiotherapy, investigational agents) if the disease has no progression
during one year.
8. At least one measurable lesion by CT or MRI. The measureable lesion should receive no
local treatments (i.e., radiotherapy) or not used for screening biopsies (If there is
only one target lesion that must be biopsied, baseline tumor evaluation is required at
least 14 days after screening biopsy) and can be accurately measured at baseline with
the longest diameter greater than 10 mm at baseline (if it is a lymph node, short
diameter greater than 15 mm is required). If the lesions located at the regions which
were previously treated are confirmed to progress, they can be chosen as lesion
according to RECIST Version 1.1
9. Females who have fertility potential before menopause should have a pregnancy test in
the time period of 7 days prior to start of dosing, should not be breast feeding and
must have a negative pregnancy test (blood test or urinalysis) prior to start of
dosing; Males and females of child-bearing age must take adequate contraceptive
measures within 3 months after signing the informed consent of the study to the last
1. Treatment with any of the following:
- Prior treatment with any systemic anti-cancer therapy for locally
advanced/metastatic NSCLC, such as standard chemotherapy, targeted therapy,
biological therapy, immune therapy and for the prior adjuvant / neo-adjuvant
therapy listed in the inclusion criteria VII
- Patients received other systemic anticancer therapies for advanced/metastatic
non-small cell lung cancer
- Patients who have received intrapleural perfusion therapy should be admitted to
the group unless the stabilization of hydrothorax is longer than 28 days
- Prior treatment with an EGFR-TKI
- Major surgery within 4 weeks of the first dose of study drug
- Radiotherapy treatment to more than 30% of the bone marrow or with a wide field
of radiation within 4 weeks of the first dose of study drug and local
radiotherapy or palliative radiotherapy for bone metastasis within 14 days before
first drug administration
- Patients receiving medications or herbal supplements known to be potent
inhibitors or inducers of cytochrome P450 (CYP) 3A4 within 7 days before first
drug administration and patients continuously taking these medications during
- Patients taking traditional Chinese medicine and preparations whose therapeutic
goal is anti-tumors within 7 days before first drug administration; or
continuously taking these medications during investigating period
- Patients with any factors that increase the risk of QTc prolongation or risk of
Torsade ventricular tachycardia event who continuously take these medications
during investigating period.
- Before the first administration, the duration of discontinuation of other
clinical experimental drugs was less than 14 days
2. Unrecovered toxic reaction due to anti-tumor therapy existed, with over 1 grade of
CTCAE (except alopecia) or 2 grade if ever applied DDP curing related neuropathy; Bone
marrow, liver and kidney organ function please refer to exclusion criteria 7.
3. The tissue type is mixed type, that is, patients with lung adenocarcinoma mixed with
lung squamous cell carcinoma.
4. Patients with spinal cord compression, asymptomatic and stable brain metastases,
except for those patients who have completion of the definitive therapy and steroids
at least 28 days before investigation，or patients who received local radiotherapy for
brain metastasis will be allowed in when the period of stabilization of brain
metastases are at no shorter than 28 days.
5. Patients with other malignant tumors or have a history of other malignant tumors,
except for basal cell carcinoma of the skin, carcinoma in situ of the cervix and
ductal carcinoma in situ of the breast.
6. Any condition affecting the drug taking, or significantly affecting the absorption or
the pharmacokinetic parameters, include any kind of uncontrollable nausea or vomit,
chronic gastroenteropathy, disability in swallowing, history of gastrointestinal
resection or surgery, uncured recurrent diarrhea, atrophic gastritis (the age of onset
is less than 60 years old), stomach diseases, crohn's disease and ulcerative colitis
that require long-term use of PPI antiacid drugs without cure.
7. Patients of organ insufficiency in bone marrow, liver and kidney meet the following
requirements (patients should receive no blood transfusion, blood product,
hematopoietic stimulating factors, and albumin two weeks before blood sampling of
- Absolute neutrophil count < 1.5 x 109/L, Platelet count < 75 x109/L, Haemoglobin
< 90 g/L;
- Alanine aminotransferase/Aspartate aminotransferase > 2.5 times the upper limit
of normal (ULN) if no demonstrable liver metastases or > 5 times in the presence
of liver metastases;
- Total bilirubin > 1.5 times ULN, or >3 times ULN in the presence of definitive
Gilbert's syndrome (Unbound hyperbilirubinemia) or liver metastases;
- Creatinine >1.5 times ULN concurrent with creatinine clearance < 50 ml/min
(measured or calculated by Cockcroft and Gault equation);
- The international standardized ratio (INR) was > and 1.5, and the partial
activation time of prothrombin (APTT) was > 1.5 times ULN.
8. Any condition meets the following cardiac standard:
- Mean resting corrected QT interval (QTc)>470 msec, obtained from 3 ECG, using the
screening clinic ECG machine-derived QTc value.
- Any clinically important abnormalities in rhythm, conduction, or morphology of
resting ECG, e.g., complete left bundle branch block, third-degree heart block,
second-degree heart block, PR interval >250 msec
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic
events such as heart failure, hypokalaemia, congenital long QT syndrome, family
history of long QT syndrome, or unexplained sudden death under 40 years of age in
first-degree relatives or any concomitant medication known to prolong the QT
- Echocardiographic examination: LVEF<50%
9. Active infection with HBV, HCV, or HIV. All subjects will be screened for HBV, HCV, or
Or HIV infection during the screening period:
- HBsAg positive, HBV DNA ≥1000cps/ml（or200IU/ml）
- Anti-HCV antibody was positive and HCV RNA was positive
- HIV antibody was positive
10. Interstitial lung disease, drug - induced interstitial pulmonary disease, history of
radiation pneumonia which required steroid treatment; acute or progressive pulmonary
symptoms may occur at baseline or interstitial pulmonary disease may be identified
that the researchers considered not suitable for trail
11. Allergy to the study drug and/or its excipients is known or suspected
12. Women during pregnancy or lactation
13. Judgment by investigator that the patients should participate in the study if the
patient is unlikely to comply with study procedure, restrictions, and requirements
(for example, uncontrolled hypertension, uncontrolled diabetes, active bleeding