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

Inclusion Criteria:

1. Volunteer to participate in clinical research; To fully understand and understandthis study and to sign the Informed Consent Form (ICF); Willing to follow and ableto complete all test procedures;

2. The age of signing ICF is ≥ 18 years old and ≤ 75 years old;

3. Esophageal Squamous Cell Carcinoma (ESCC) confirmed by histopathology or cytology;

4. Previous failure or progression of at least one standard systemic therapy forcervical cancer, or intolerability toxicity (CTCAE≥3 adverse events);

5. Within 4 weeks prior to the first administration of the medication, at least onemeasurable target lesion must be evaluated according to the RECIST v1.1 criteria;

6. Tumor tissue should be provided as much as possible for an evaluable PD-L1expression result at Screening period；

7. Before the initial administration of the study drug, there should be at least a 3-week interval or 5 times the half-life of the last cytotoxic chemotherapy,immunotherapy, or biological therapy, whichever is shorter. There should be at leasta 2-week interval from the previous small molecule targeted therapy, at least a 1-week interval from traditional Chinese medicine treatment with antitumorindications or minor surgery. Additionally, treatment-related adverse events (AEs)should have recovered to NCI-CTCAE grade ≤ 1 (except for grade 2 peripheralneurotoxicity and alopecia)；

8. The ECOG physical performance score of 0-1 in the week prior to randomization；

9. Expected survival ≥ 3 monthes；

10. Laboratory tests within the previous week confirm adequate organ function (within 14days prior to the first dose of medication, without receiving interventions such asblood transfusions or granulocyte colony-stimulating factor)；

11. Male and female subjects of childbearing potential must agree to use at least onehighly effective method of contraception during the trial and for at least 6 monthsafter the last dose of the study drug. Female subjects of childbearing potentialmust have a negative pregnancy test within 7 days prior to enrollment.

Exclusion Criteria:

1. History of any second malignant tumor within the first 2 years prior torandomization;

2. BMI <17.5 kg/m2；

3. Symptomatic, untreated, or progressively worsening central nervous system (CNS) orleptomeninges metastases;

4. After appropriate intervention, uncontrollable pleural effusion, pericardialeffusion 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, orsuspected ILD cannot be ruled out by imaging at the time of screening; Or there arelung 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 leftventricular ejection fraction (LVEF) < 50%; (2) unstable angina; (3) myocardialinfarction or cerebrovascular accident within the last 6 months (excluding lacunarinfarction, minor ischemic stroke, or transient ischemic attack); (4) uncontrolledarrhythmias (including QTc interval ≥ 450 ms for males, ≥ 470 ms for females) (QTcinterval calculated by Fridericia's formula); (5) poorly controlled hypertension (systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHgdespite active treatment);

7. Subjects who are preparing for or have previously received an organ or bone marrowtransplant;

8. Within the 2 weeks prior to randomization, there is the presence of an activesystemic infectious disease requiring intravenous antibiotic treatment;

9. Used strong inhibitors or strong inducers of CYP2D6 or CYP3A within 2 weeks prior torandomization;

10. Received systemic corticosteroids (prednisone >10 mg/day or an equivalent dose ofsimilar drugs) or other immunosuppressive treatments within 14 days prior to thefirst dose; with the following exceptions: use of topical, ophthalmic,intra-articular, intranasal, and inhaled corticosteroids; short-term use ofcorticosteroids for prophylactic treatment during situations such as the use ofcontrast agents;

11. A history of ≥ Grade 3 immune-related adverse events during previous immunotherapy;

12. Active or suspected autoimmune disease. Patients with autoimmune-relatedhypothyroidism who are undergoing thyroid hormone replacement therapy are permittedto participate in the study; patients with controlled Type 1 diabetes mellitusreceiving 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 vaccinesfor seasonal influenza is permitted;

14. Known history of severe allergic reactions to macromolecular proteinpreparations/monoclonal antibodies, or allergy to components of the trial drugformulation;

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 themunsuitable for participation in this trial.