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

The study is being conducted to explore the reasonable dosage and evaluate the efficacy, safety and tolerability of HLX43 (Anti-PD-L1 ADC) in Patients with Recurrent/Metastatic Esophageal Squamous Cell Carcinomar (ESCC) Failed or Intolerance to Standard First-Line Therapy.

This study is an open-label phase II clinical study to explore the reasonable dosage and evaluate the efficacy, safety and tolerability of HLX43 (Anti-PD-L1 ADC) in Patients with Recurrent/Metastatic Esophageal Squamous Cell Carcinomar (ESCC) Failed or Intolerance to Standard First-Line Therapy.

In this study, eligible subjects will be randomized at 1:1:1 ratio, and the patients will be administered with HLX43 at different doses via intravenous infusion.

Eligibility Criteria:
Inclusion Criteria:

1. Volunteer to participate in clinical research; To fully understand and understand this study and to sign the Informed Consent Form (ICF); Willing to follow and able to 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 for cervical cancer, or intolerability toxicity (CTCAE≥3 adverse events);
5. Within 4 weeks prior to the first administration of the medication, at least one measurable 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-L1 expression 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 least a 2-week interval from the previous small molecule targeted therapy, at least a 1-week interval from traditional Chinese medicine treatment with antitumor indications or minor surgery. Additionally, treatment-related adverse events (AEs) should have recovered to NCI-CTCAE grade ≤ 1 (except for grade 2 peripheral neurotoxicity 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 14 days prior to the first dose of medication, without receiving interventions such as blood transfusions or granulocyte colony-stimulating factor)；
11. Male and female subjects of childbearing potential must agree to use at least one highly effective method of contraception during the trial and for at least 6 months after the last dose of the study drug. Female subjects of childbearing potential must 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 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. A history of ≥ Grade 3 immune-related adverse events during previous immunotherapy;
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;
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.