Patients with previously untreated advanced or metastatic esophageal squamous cell carcinoma are recruited to this prospective non-randomized study comprising two separate cohorts. Patients will receive SHR-1210, a novel anti-PD-1 antibody, with apatinib and either irinotecan or paclitaxel liposome plus nedaplatin. The primary endpoint is to determine the objective response rate (ORR) of patients in both cohorts. The regimen(s) of promising efficacy will be further verified in subsequent randomized studies to define the optimal combination of immunotherapy, anti-angiogenesis and chemotherapy in advanced esophageal cancer patients.

Inclusion Criteria:

1. Histologically or cytologically confirmed squamous cell carcinoma of the esophagus, locally advanced, unresectable, recurrent or metastatic disease.
2. Have not received prior systemic therapy.
3. Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
4. Eastern Collaborative Oncology Group (ECOG) Performance Status ≤ 1.
5. Life expectancy >12 weeks.
6. Adequate organ function.
7. For females of child bearing potential, a negative urine or serum pregnancy test result within 72h before study treatment. Participants of reproductive potential must be willing to use adequate contraception for the course of the study until 2 months after the last dose of any of the drugs in the study.
8. Willing and able to provide written informed consent and comply with the requirements of the study.

Exclusion Criteria:

1. Any previous malignancy, except for non squamous-cell carcinoma of skin or carcinoma-in-situ of the uterine cervix within 5 years prior to study entry.
2. Known central nervous system (CNS) metastases.
3. Prior therapy with any of the immune check-point inhibitors.
4. Known immediate or delayed hypersensitivity reaction to SHR-1210, apatinib, irinotecan, paclitaxel liposome, nedaplatin or their excipients.
5. Subjects with any active autoimmune disease or history of autoimmune disease.
6. Known Human Immunodeficiency Virus (HIV) infection, active Hepatitis B or Hepatitis C infection.
7. Concurrent medical condition requiring the use of cortisol (>10mg/day prednisone or equivalent dose) or other systematic immunosuppressive medications within 14 days before the study treatment. Except: inhalation or topical corticosteroids no more than 10 mg/day prednisone or equivalent.
8. Received a live vaccine within 4 weeks of the first dose of study medication.
9. Hypertension with a blood pressure of systolic> 140 millimeter of mercury (mm Hg) and/or diastolic > 90 mm Hg that is not effectively controlled by anti-hypertensive therapy.
10. Uncontrolled clinically significant heart disease, including but not limited to the following: (1) > NYHA II congestive heart failure; (2) unstable angina, (3) myocardial infarction within the past 1 year; (4) clinically significant supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention.
11. Unable to swallow oral medications or with gastrointestinal disorders that might interfere with proper absorption of oral drugs.
12. Active digestive ulcer disease, inflammatory bowel disease, intestinal obstruction or any other condition that, in the clinical judgment of the Principal Investigator, may cause severe gastrointestinal bleeding or perforation.
13. Active infection or an unexplained fever > 38.5°C before 4 weeks of enrollment.
14. Unstable pulmonary embolism, deep vein thrombosis, or other significant arterial/venous thromboembolic conditions.
15. Pregnant or lactating female.
16. Familial, sociological or geographical conditions that, in the clinical judgment of the Principal Investigator, do not permit compliance with the protocol.