The purpose of this study is to evaluate the efficacy and safety of KC1036 versus investigator's choice of chemotherapy in patients with advanced recurrent or metastatic esophageal squamous cell carcinoma

This is a randomized, controlled, open-label, multicenter phase III trial. Patients with advanced recurrent or metastatic esophageal squamous cell carcinoma that has received PD-1 or PD-L1 inhibitors and at least second-line systemic therapy will be randomized at a 1: 1 ratio to receive KC1036 or the investigator's choice of chemotherapy (Irinotecan/Docetaxel/S-1) until confirmed disease progression assessed by the RECIST V1.1 standard, death, intolerable toxicity, initiation of a new anti-tumor therapy, other reasons leading to treatment discontinuation as specified by protocol.

Inclusion Criteria:

• Males or females aged 18 to 75 years;
• Histologically or cytologically confirmed esophageal or esophageal-gastric junction squamous cell carcinoma;
• Patient with advanced recurrent or metastatic esophageal squamous cell carcinoma previously treated with a PD-1 or PD-L1 inhibitor and at least second-line systemic therapy;
• At least one measurable tumor lesion according to RECIST 1.1;
• Eastern Cooperative Oncology Group performance status score of 0 or 1;
• Life expectancy > 12 weeks;
• BMI≥16.0 and weight≥40 kg ;
• Adequate bone marrow, renal, and hepatic function;
• Female patients of childbearing potential with a negative blood pregnancy test completed within 7 days before randomization；
• Patients should participate in the study voluntarily and sign informed consent.

Exclusion Criteria:

• Any patient who is known to have untreated central nervous system (CNS) metastasis;
• Other kinds of malignancies within 5 years;
• Gastrointestinal abnormalities;
• Cardiovascular and cerebrovascular diseases;
• Prior therapies with vascular targeting inhibitor；
• Previously treated with Irinotecan, Docetaxel and Tegafur Gimeracil Oteracil Potassium；
• Involved in other clinical trials within 4 weeks before enrollment；Prior anti-tumor therapies with radiotherapy, immunotherapy, operation within 4 weeks before enrollment;Prior anti-tumor therapies with small molecule targeting drugs within 2weeks or 5 half-lives (whichever is longer) before enrollment; Prior anti-tumor therapies with chemotherapy within 3 weeks or 5 half-lives (whichever is longer) before enrollment;
• Presence of unresolved toxicities from prior anti-tumor therapy, defined as having not resolved to NCI CTCAE 5.0 Grade 0 or 1;
• Uncontrolled massive ascites, pleural or pericardial effusion;
• Severe infection within 4 weeks prior to randomization (CTCAE > Grade 2);
• Known history of human immunodeficiency virus (HIV) infection or current active hepatitis B or C infection;
• Pregnant or lactating women;
• Female subjects of child-bearing potential and male subjects of reproductive capacity who do not agree to use contraceptive measures during the study and for 6 months after the end of the study.
• Other patients are not eligible for enrollment assessed by investigators.