The goal of this clinical trial is Iparomlimab and tuvonralimab (QL1706) combined with chemoradiotherapy in the treatment of locally advanced esophageal cancer after failed neoadjuvant chemoimmunotherapy. The main question it aims to answer is： Can it bring survival benefits and safet to patients？Subsequent evaluation will determine whether the patient undergoes surgical treatment. Follow-up will be conducted to assess the efficacy and safety of the treatment。

Participants were treated with QL1706 and radical CCRT.After receiving the combination of QL1706 with radical CCRT, patients who are eligible for surgery will undergo the procedure, while those who are not candidates for surgery may receive sequential boost radiotherapy to PGTV at a about dose of 60 Gy. Following radiotherapy, maintenance treatment with immunotherapy combined with chemotherapy will be administered for up to one year, until disease progression, death, or the occurrence of intolerable toxicity.

Inclusion Criteria:

• Age 18 to 75 years, male or female;

  • Histologically confirmed locally advanced squamous cell carcinoma or adenocarcinoma of the esophagus or esophagogastric junction;

    • ECOG performance status 0-1; ④ Failure of or local progression after 2-4 cycles of first-line chemotherapy combined with immunotherapy, or deemed unresectable by surgical evaluation;

      ⑤ At least one measurable lesion according to RECIST v1.1 criteria;

      ⑥ Adequate major organ and bone marrow function: Hematology: Hemoglobin (Hb) ≥90 g/L (without transfusion within 14 days); Absolute neutrophil count (NEUT) ≥1.5×10⁹/L; Platelets (PLT) ≥100×10⁹/L; Biochemistry: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN (≤5×ULN in cases of liver metastases); Total bilirubin (TBIL) ≤2×ULN; Serum albumin (ALB) ≥28 g/L; Serum creatinine (Cr) ≤1.5×ULN and creatinine clearance >50 μmol/L; Coagulation: International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤1.5×ULN (unless the subject is receiving anticoagulant therapy and INR and APTT are within the expected therapeutic range);

      ⑦ Effective contraception during the study period;

      • Voluntary participation in this study with signed informed consent and good compliance.

Exclusion Criteria:

• Active bleeding or high risk of bleeding (as assessed by the investigator);

  • Patients requiring systemic anti-infective therapy;

    • Concurrent primary malignant tumors other than esophageal cancer (excluding cured basal cell carcinoma of the skin and carcinoma in situ of the cervix);

      • Presence of brainstem, leptomeningeal metastasis, spinal cord metastasis, or compression;

        • Complicated with severe cardiovascular diseases, such as uncontrolled heart failure, coronary heart disease, cardiomyopathy, uncontrolled arrhythmia, uncontrolled hypertension, or history of myocardial infarction within the past 5 years; and complicated with other uncontrolled acute or chronic diseases;

          • Positive for human immunodeficiency virus antibody (HIVAb), active tuberculosis, active hepatitis B virus infection (HBsAg positive and HBV-DNA > 500 IU/ml or the upper limit of normal, whichever is higher), or active hepatitis C virus infection (HCV antibody positive and HCV-RNA > lower limit of detection);

            • Known allergy to any component of any study drug; known history of severe hypersensitivity reactions to other monoclonal antibodies; ⑧ Adverse reactions from prior immunotherapy not fully recovered;

              • Receiving systemic glucocorticoid therapy (excluding nasal spray, inhalation, or other topical glucocorticoids) or any other form of immunosuppressive therapy within 7 days prior to the first study drug administration;

                ⑩ Active autoimmune disease requiring systemic treatment (e.g., disease-modifying drugs, glucocorticoids, or immunosuppressants) within 2 years prior to study administration. Replacement therapies (e.g., thyroxine, insulin, or physiologic glucocorticoids for adrenal or pituitary insufficiency, etc.) are not considered systemic treatments;

                ⑪ Known history of mental illness, substance abuse, alcoholism, or drug addiction;

                ⑫ Pregnant or breastfeeding women;

                ⑬ Other conditions deemed unsuitable for participation in this study by the investigator, including but not limited to poor patient compliance, intolerance, etc.