This is an open-label, phase II study of KN046 combined with chemotherapy and palliative radiotherapy in patients with recurrent or metastatic esophageal squamous cell carcinoma to evaluate the safety, efficacy and tolerance.

Inclusion Criteria:

• Signed inform consent form(ICF)
• Age ≥ 18 years and ≤ 75 years, male or female
• Histologically or cytologically documented recurrent or metastatic esophageal squamous cell carcinoma, with indications of radiotherapy and without prior systemic treatment
• At least one measurable lesion according to Response Evaluation Criteria In Solid Tumors（RECISIT） v 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ function
• Female patients and males with partners of childbearing potential should be using highly effective contraceptive measures (failure rate of less than 1% per year). Contraception should be continued for a period of 24 weeks after dosing has been completed.
• Ability to comply with treatment, procedures and pharmacokinetics (PK) sample collection and the required study follow-up procedures

Exclusion Criteria:

• Known brain metastasis or another Central Nervous System (CNS) metastasis that is either symptomatic or untreated.
• Patients who are participating or have participated in a study of an investigational drug within 4 weeks prior to the first dose of trial treatment.
• Patients who have received immune checkpoint proteins/antibody/medicine for treatment.
• Patients who have interstitial lung disease, or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management.
• Subjects with active autoimmune diseases or history of autoimmune diseases should be excluded
• Active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection.
• Known HIV infection or known history of acquired immune deficient syndrome (AIDS)
• Any unresolved the Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 2 toxicities from prior anti-cancer therapy except for vitiligo, alopecia
• Patients who have serious hypersensitive reaction to monoclonal antibodies and have history of uncontrolled allergic asthma