a phase ii clinical study to evaluate hlx43 in patients with recurrent/metastatic escc failed or intolerance to standard therapy

Conditions: Esophageal Cancer

Summary: 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) \ 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.