| Eligibility |
Inclusion Criteria:
1. histologically confirmed esophagus squamous cell carcinoma (ESCC);
2. metastatic or unresectable disease;
3. previously treated with at least 1 line of platinum based chemotherapy regimens
(including cisplatin or carboplatin);
4. Less than 6 months after the most recent treatment, with documented disease
progression by imaging studies according to RECIST 1.1 criteria;
5. presence of at least one measurable lesion according to RECIST 1.1. (the measurable
lesion cannot be the biopsy lesion)
6. adequate hematopoietic function which is defined as below:
1. hemoglobin level = 9 g/dL;
2. absolute neutrophil count (ANC) = 1,500/mm3;
3. platelet count = 100,000/mm3;
7. adequate hepatic function which is defined as below:
1. total bilirubin < 2 mg/dL;
2. Alanine aminotransferase (ALT) = 3 x ULN;
8. adequate renal function: creatinine clearance rate (CCr) = 50 mL/min ((based upon
24-hour urine collection or calculated by Cockroft-Gault formula); < Cockroft-Gault
formula > Male: ((140 - age) × weight [kg])/(72 × serum creatinine[mg/dL]) Female:
0.85 x estimate for male
9. age of 20 years or above;
10. ECOG performance status 0-1;
11. life expectancy of at least 12 weeks;
12. ability to take oral medication;
13. ability to understand and willingness to sign a written informed consent document.
14. Subjects with chronic hepatitis B virus infection (HBV surface antigen (HBsAg)
positive) must start antiviral therapy with nucleoside analogs (e.g., entecavir or
tenofovir, according to current practice guidelines) before start of study drug
treatment and maintained throughout the experimental therapy.
Exclusion Criteria:
1. Any investigational treatment, anti-tumour treatment within 4 weeks or within 5
half-life periods (whichever is shorter) prior to the initiation of trial treatment.
2. Major surgery ('major' according to the Investigator's assessment) performed within 12
weeks prior to first trial treatment or planned within 12 weeks after screening, e.g.,
hip replacement.
3. Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTc) >470 msec.
- Any clinically important abnormalities (as assessed by the Investigator) in
rhythm, conduction, or morphology of resting ECGs, e.g., complete left bundle
branch block, third degree heart block.
- 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, or
any concomitant medication known to prolong the QT interval.
- Patients with an ejection fraction (EF) <55% or the lower limit of normal of the
institutional standard (if the lower limit of normal of institutional standard is
higher than 55%) will be excluded. Only in cases where the Investigator (or the
treating physician or both) suspects cardiac disease with negative effect on the
EF will the EF be measured during screening using an appropriate method according
to local standards to confirm eligibility (e.g., echocardiogram, multi-gated
acquisition scan). An historic measurement of EF no older than 6 months prior to
first administration of trial drug can be accepted provided that there is
clinical evidence that the EF value has not worsened since this measurement in
the opinion of the Investigator or of the treating physician or both.
4. Known history of human immunodeficiency virus infection.
5. Active autoimmune disease or a documented history of autoimmune disease, except
vitiligo or resolved childhood asthma/atopy.
6. Known history of severe hypersensitivity reactions to other mAbs or known
hypersensitivity to the trial drugs or their excipients.
7. Known presence of symptomatic central nervous system (CNS) metastases, unless
asymptomatic and off corticosteroids and anti-convulsant therapy for at least 2 weeks
prior start of treatment.
8. Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within
4 weeks prior to the first dose of study treatment.
9. Men who plan to father a child while in the trial and for at least 6 months after the
last administration of trial medication.
10. Other malignancy within the past 5 years except for adequately treated basal or
squamous cell skin cancer or cervical cancer in situ.
11. Previously treated with any PD-1 inhibitors, PD-L1 inhibitors, or CTLA-4 inhibitors.
12. Previously treated with gefitinib, erlotinib, afatinib, osimertinib.
13. History or known presence of interstitial pneumonia.
14. Presence of grade 2 or above ascites or pleural effusion.
15. Presence of grade 2 or above diarrhea.
16. Presence of mental disease or psychotic manifestation.
17. Active or uncontrolled infection.
18. significant medical conditions that is contraindicated to study medication or render
patient at high risk from treatment complications based on investigator's discretion;
19. pregnant women or nursing mothers, or positive pregnancy test for women of
childbearing potential. Patients with childbearing potential shall have effective
contraception for both the patient and his or her partner during the study.
20. Received a live vaccine within 30 days prior to the first dose of trial treatment.
Seasonal flu vaccines that do not contain live virus are permitted.
21. Patients with tracheo-esophageal fistula or broncho-esophagal fistula.
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