Z650 in Advanced Esophageal Squamous Cell Carcinoma With EGFR Over Expression or Gene Amplification

Inclusion Criteria:

* Histologically or cytologically confirmed Stage IIIB or IV ESCC
* At least experienced one regimens of chemotherapy prior to study
* Histological or cytological evidence of EGFR overexpression or gene copy number increased
* Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
* Toxicity recovered to NCI CTCAE v.4.03 Grade ≤1 from previous treatments (except alopecia)
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
* Life expectancy of ≥ 12 weeks
* Adequate organ function
* Subject Consent
* Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to performing this study.
* Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

* Prior treatments
* EGFR targeted therapy, or major surgery within 4 weeks prior to study treatment
* Nitrosourea and mitomycin chemotherapy within 6 weeks prior to study treatment
* Had received any investigational agent from other clinical study within 4 weeks prior to study treatment or are currently participating in other clinical trials
* Gastrointestinal diseases that could affect the absorption of Z650, (e.g., serious swallowing obstruction, chronic diarrhea, bowel obstruction);
* Symptomatic, untreated or unstable central nervous system metastases (patient are only permitted if treated, asymptomatic and stable for at least 4 weeks prior to start of study treatment)
* History of interstitial lung disease
* Uncontrolled hypertension that require more than two anti-hypertensive agents to control, or systolic blood pressure (BP) \>140mmHg or diastolic BP \>90 mmHg before the first administration
* Doppler ultrasound evaluation of Left ventricular ejection fraction \< 50%
* Male with QTc interval \> 450 ms or female with QTc interval \> 470 ms
* History of immunodeficiency, or other acquired or congenital immunodeficiency, or history of organ transplantation
* Any disease of the following bellowed within 6 months prior to administration:

Myocardial infarction, or unstable angina, coronary or peripheral artery bypass graft, congestive heart failure, or cerebrovascular events (including transient ischemic attack)

* Active infection of hepatitis B virus (HBV)/hepatitis C virus (HCV), or infection of Human immunodeficiency virus (HIV)
* Other malignancies within 5 years prior to enrollment, with the exception of carcinoma in situ of the cervix, basal or squamous cell skin cancer
* History of serious allergic reactions attributed to excipients of Z650, including mannitol, sodium carboxymethyl starch, aerosol, magnesium stearate and silicified microcrystalline cellulose
* Pregnant women, or patients not agree to use of effective contraceptions during the study or within 6 month after the study
* Any other reason the investigator considers the patient is not suitable to participate in the study