A Phase II Clinical Study to Evaluate HLX43 in Patients With Recurrent/Metastatic ESCC Failed or Intolerance to Standard Therapy

Exclusion Criteria

• •1. History of any second malignant tumor within the first 2 years prior to randomization;
• •2. BMI \<17.5 kg/m2；
• •3. Symptomatic, untreated, or progressively worsening central nervous system (CNS) or leptomeninges metastases;
• •4. After appropriate intervention, uncontrollable pleural effusion, pericardial effusion or ascites still need to be drained frequently;
• •5. A history of ≥ grade 3 radiation pneumonia; A history of (non-infectious) interstitial lung disease (ILD) requiring steroid use, or a current ILD, or suspected ILD cannot be ruled out by imaging at the time of screening; Or there are lung diseases leading to clinical severe respiratory impairment;
• •6. Subjects exhibit poorly controlled cardiovascular clinical symptoms or diseases, including but not limited to: (1) NYHA class II or above heart failure, or left ventricular ejection fraction (LVEF) \< 50%; (2) unstable angina; (3) myocardial infarction or cerebrovascular accident within the last 6 months (excluding lacunar infarction, minor ischemic stroke, or transient ischemic attack); (4) uncontrolled arrhythmias (including QTc interval ≥ 450 ms for males, ≥ 470 ms for females) (QTc interval calculated by Fridericia's formula); (5) poorly controlled hypertension (systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg despite active treatment);
• •7. Subjects who are preparing for or have previously received an organ or bone marrow transplant;
• •8. Within the 2 weeks prior to randomization, there is the presence of an active systemic infectious disease requiring intravenous antibiotic treatment;
• •9. Used strong inhibitors or strong inducers of CYP2D6 or CYP3A within 2 weeks prior to randomization;
• •10. Received systemic corticosteroids (prednisone \>10 mg/day or an equivalent dose of similar drugs) or other immunosuppressive treatments within 14 days prior to the first dose; with the following exceptions: use of topical, ophthalmic, intra-articular, intranasal, and inhaled corticosteroids; short-term use of corticosteroids for prophylactic treatment during situations such as the use of contrast agents;
• •11. History of adverse events leading to permanent discontinuation of immunotherapy; or a history of grade 2 or higher immune-related pneumonitis or myocarditis;
• •12. Active or suspected autoimmune disease. Patients with autoimmune-related hypothyroidism who are undergoing thyroid hormone replacement therapy are permitted to participate in the study; patients with controlled Type 1 diabetes mellitus receiving insulin therapy are also allowed to participate in the study;
• •13. Live vaccinations or attenuated live vaccinations should not be administered within 4 weeks prior to the initial dosing. Administration of inactivated viral vaccines for seasonal influenza is permitted;
• •14. Known history of severe allergic reactions to macromolecular protein preparations/monoclonal antibodies, or allergy to components of the trial drug formulation；previous treatment with antibody-drug conjugates (ADCs) using a topoisomerase I inhibitor as the payload;
• •15. Active tuberculosis;
• •16. Human immunodeficiency virus (HIV) infection;
• •17. Pregnant or lactating women;
• •18. The researcher deems that the subject has any other factors that make them unsuitable for participation in this trial.