Combination of Cadonilimab and Chemoradiotherapy in Esophageal Cancer (EC-CRT-006)

Inclusion Criteria: 1. Histologically confirmed squamous cell carcinoma of the esophagus; 2. Locally advanced, and absence of distant metastasis disease, confirmed by endoscopic ultrasound (EUS) and PET-CT scan, stage II-IVA (according to UICC TNM version 8); 3. Not suitable for surgery (either for medical reasons or patient's choice); 4. Age at diagnosis 18 to 75 years; 5. No prior cancer therapy; 6. Estimated life expectancy \>6 months; 7. Eastern Cooperative Oncology Group performance status ≤ 2 8. No history of concomitant or previous malignancy; 9. The function of important organs meets the following requirements: a. white blood cell count (WBC) ≥4.0×109/L, absolute neutrophil count (ANC) ≥1.5×109/L; b. platelets ≥100×109/L; c. hemoglobin ≥9g/dL; d. serum albumin ≥2.8g/dL; e. total bilirubin ≤1.5×ULN, ALT, AST and/or AKP ≤2.5×ULN; f. serum creatinine ≤1.5×ULN or creatinine clearance rate \>60 mL/min; 10. Ability to understand the study and sign informed consent. Exclusion Criteria: 1. Patients who have been treated previously with anti-tumor therapy (including chemotherapy, radiotherapy, surgery, immunotherapy, etc.); 2. Patients with distant metastasis disease or esophageal fistula at diagnosis; 3. Known or suspected allergy or hypersensitivity to monoclonal antibodies, any ingredients of cadonilimab, and the chemotherapeutic drugs paclitaxel or cisplatin; 4. Patients who have a preexisting or coexisting bleeding disorder; 5. Female patients who are pregnant or lactating; 6. Inability to provide informed consent due to psychological, familial, social and other factors; 7. Presence of CTC grade ≥2 peripheral neuropathy; 8. A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer 9. A history of diabetes for more than 10 years and poorly controlled blood glucose levels; 10. Patients who cannot tolerate chemoradiotherapy due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia. 11. Active autoimmune diseases, a history of autoimmune diseases (including but not limited to these diseases or syndromes, such as colitis, hepatitis, hyperthyroidism), a history of immunodeficiency (including a positive HIV test result), or other acquired or congenital immunodeficiency diseases, a history of organ transplantation or allogeneic bone marrow transplantation; 12. A history of interstitial lung disease or non-infectious pneumonia; 13. A history of active pulmonary tuberculosis infection within 1 year or a history of active pulmonary tuberculosis infection more than 1 year ago but without formal anti-tuberculosis treatment; 14. Presence of active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (positive for hepatitis C antibody, and HCV-RNA levels higher than the lower limit of the assay).