A Phase II Study to Evaluate the Efficacy and Safety of HLX43 + Serplulimab as Neoadjuvant Therapy in Subjects With NSCLC

Exclusion Criteria

• •1\. Histologically or cytologically confirmed tumor containing components of small cell lung cancer or neuroendocrine carcinoma;
• •2\. Any prior systemic or local anti-tumor therapy for non-small cell lung cancer, including chemotherapy, radiotherapy, or immunotherapy;
• •3\. History of any second malignancy within 2 years prior to randomization, except for early-stage malignancies (carcinoma in situ or stage I tumors) that have received radical treatment, such as non-melanoma skin cancer, cervical carcinoma in situ, localized prostate cancer, ductal carcinoma in situ of the breast, and papillary thyroid carcinoma;
• •4\. History of adverse events leading to permanent discontinuation of immunotherapy, or history of ≥ Grade 2 immune-related pneumonitis or immune-related myocarditis;
• •5\. Subjects with current or prior history of clinically significant pulmonary impairment due to pulmonary comorbidities, including but not limited to any underlying lung disease (e.g., pulmonary embolism within 3 months prior to the first dose, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, interstitial pneumonitis, pneumoconiosis, drug-related pneumonitis, and pleural effusion), any autoimmune, connective tissue, or inflammatory disease that may involve the lungs (i.e., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis), prior pneumonectomy that may interfere with the detection and management of suspected drug-related pulmonary toxicity, or history of radiation pneumonitis within 6 months;
• •6\. Patients with any poorly-controlled cardiovascular and cerebrovascular clinical symptoms or diseases, including but not limited to: (1) NYHA Class II or greater heart failure or left ventricular ejection fraction (LVEF) \< 50%; (2) unstable angina pectoris; (3) myocardial infarction or cerebrovascular accident within 6 months (except lacunar infarction, slight cerebral ischemia, or transient ischemic attack); (4) poorly controlled arrhythmia (including QTc interval ≥ 470 ms) (QTc interval is calculated by Fridericia's formula); (5) poorly-controlled hypertension (systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg after active treatment);
• •7\. Patients with active systemic infectious diseases requiring intravenous antibiotics within 2 weeks prior to randomization;
• •8\. Patients who have previously received other antibodies/drugs against immune checkpoints, such as PD-1, PD-L1, CTLA4, etc.;
• •9\. Patients who have used moderate or potent CYP2D6 or CYP3A inhibitors or inducers within 2 weeks prior to randomization;
• •10\. Patients who have received systemic corticosteroids (prednisone \> 10 mg/d or equivalent dose of similar drug) or other immunosuppressants within 2 weeks prior to randomization; Except: patients treated with topical, ocular, intra-articular, intranasal, and inhaled corticosteroids; short-term prophylactic use of corticosteroids for contrast agents, etc.;
• •11\. Patients with known active or suspected autoimmune diseases. Patients with autoimmune-related hypothyroidism and receiving thyroid hormone replacement therapy and those with type 1 diabetes mellitus controlled with insulin therapy are eligible to be enrolled;
• •12\. Patients who have received a live vaccine or live attenuated vaccine within 4 weeks prior to randomization;
• •13\. Patients who are known to have anaphylaxis to macromolecular protein preparations/monoclonal antibodies or are allergic to any component in the formulation of the investigational product;
• •14\. Patients with active tuberculosis;
• •15\. Patients with a history of immunodeficiency, including human immunodeficiency virus (HIV)-positive or other acquired or congenital immunodeficiencies, or history of organ transplantation;
• •16\. Patients with active HBV or HCV infection or HBV/HCV co-infection; Note: Patients who test positive for HBsAg or HBcAb during the screening period must undergo further HBV-DNA testing, and may be enrolled only if the test result indicates \< 500 IU/mL, \< 2500 copies/mL, or \< ULN. Patients with detectable HBV-DNA must agree to receive treatment with anti-HBV nucleos(t)ide analogs during the study.
• •Patients who test positive for HCV antibody must undergo further HCV-RNA testing, and may be enrolled only if the test result indicates \< ULN.
• •Patients with HBV/HCV co-infection (positive test for HBsAg or HBcAb and positive test for HCV antibody) should be excluded.
• •17\. Pregnant or lactating women;
• •18\. Patients who are not suitable for participating in this clinical study due to any clinical or laboratory abnormalities or other reasons as assessed by the investigator.