Clinical Study of Ivonescimab Combined With Concurrent Chemoradiotherapy in the Treatment of Advanced Non-small Cell Lung Cancer

Inclusion Criteria:

• Have fully understood this study and voluntarily signed the Informed Consent Form (ICF)

• Aged 18 to 75 years, regardless of gender

• Previously untreated, histopathologically or cytologically confirmed unresectable PD-L1 TPS ≥ 1% Stage IV non-small cell lung cancer

• Have measurable lesions according to Response Evaluation Criteria in Solid Tumors version 1.1

• Have adequate pulmonary function tests (PFTs)

• Subjects must be able to provide a prior driver gene report based on tissue or blood testing, and the test results must show that targetable driver genes such as EGFR sensitive mutations, ALK rearrangement or fusion, and ROS1 fusion are all negative; or if a certain type of driver gene is positive but the targeted drug is not available, the subject may be enrolled. If the subject does not have a driver gene test report, tumor samples (archived or fresh, primary or metastatic) or blood samples must be collected before enrollment for driver gene testing to confirm negativity (at a local laboratory or central laboratory)

• ECOG performance status score of 0-1

• Adequate organ and bone marrow function

  ① Hematology: Absolute neutrophil count (ANC) ≥ 1500/μL; Platelets ≥ 100,000/μL; Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L.

  ② Renal: Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance (CrCl) ≥ 60 mL/min (using the Cockcroft-Gault formula).

  ③ Hepar: Total bilirubin ≤ 1.5 × ULN, or for subjects with total bilirubin levels > 1.5 × ULN, direct bilirubin within normal limits; AST (SGOT) and ALT (SGPT) ≤ 2.5 × ULN.

  ④ Adequate coagulation function: International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN; Known left ventricular ejection fraction (LVEF) ≥ 50%; Urine protein < 1+ or if urine protein is 1+, further 24-hour urine protein quantification < 1.0 g.

• Endocrine System: Thyroid-stimulating hormone (TSH) within normal limits. Note: If TSH is not within the normal range at baseline, the subject may still meet the inclusion criteria if T3 and free T4 are within the normal range;Coagulation function: International Normalized Ratio (INR) or Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN, except for subjects receiving anticoagulant therapy, as long as PT or aPTT is within the intended therapeutic range of the anticoagulant drug.

• Willing and able to comply with the study plan's visits, treatment plans, laboratory tests, and other study procedures.

• Childbearing age women must have a serum pregnancy test within 3 days before the first dose, and the result must be negative. Female subjects of childbearing age and male subjects with partners of childbearing age must agree to use highly effective methods of contraception during the study and for 180 days after the last dose of the study drug.

Exclusion Criteria:

• Presence of resectable or metastatic disease
• History of interstitial lung disease, drug-induced interstitial lung disease, or radiation pneumonitis requiring steroid therapy, or currently receiving drug treatment or other clinical interventions, or presence of active pulmonary interstitial lesions or imaging findings of interstitial lung disease.
• Known history of active tuberculosis
• Known active infection requiring systemic therapy
• Any known or suspected autoimmune disease or immunodeficiency, except for: patients with a history of hypothyroidism who do not require hormone therapy or are receiving physiological doses of hormone replacement therapy; patients with stable blood glucose-controlled type 1 diabetes.
• Uncontrolled active hepatitis B (defined as positive hepatitis B surface antigen [HBsAg] test at screening with HBV-DNA levels above the upper limit of normal of the study center's laboratory; patients with HBV-DNA <500 IU/mL within 28 days before enrollment who have received at least 14 days of standard local antiviral therapy and are willing to continue antiviral therapy during the study may be enrolled); active hepatitis C (defined as positive hepatitis C virus surface antibody [HCsAb] test at screening with positive HCV-RNA).
• Known human immunodeficiency virus (HIV) infection (known HIV antibody positive)
• Vaccination with live vaccines within 30 days before the first dose, including but not limited to: mumps, rubella, measles, varicella/zoster (chickenpox), yellow fever, rabies, BCG, and typhoid vaccine (inactivated virus vaccines are allowed).
• History of severe allergic reactions to other monoclonal antibodies;
• Known severe or uncontrolled underlying diseases
• Patients with a history of another malignancy within 5 years before the first dose, other than non-small cell lung cancer, are excluded. This exclusion does not apply to malignancies with a negligible risk of metastasis or death (e.g., expected disease-free survival >5 years) that are expected to achieve a curative outcome after treatment (e.g., adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, or ductal carcinoma in situ treated with curative-intent surgery).
• Class III-IV congestive heart failure (New York Heart Association classification), poorly controlled and clinically significant arrhythmias.
• Any arterial thrombosis, embolism, or ischemia within 6 months before enrollment, such as myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack.
• Female subjects who are pregnant, breastfeeding, or planning to become pregnant during the study.
• Investigators consider other conditions that may make the patient unsuitable for participation in this clinical trial.