The treatment decisions, assessment schedule, and study procedures in this research will adhere to the routine clinical practice of each participating center. The specifics are as follows:

Treatment Decisions: Treatment will be administered in accordance with the officially approved drug label for Ivonescimab by the National Medical Products Administration (NMPA) and the latest domestic and international guidelines. Eligible patients meeting the inclusion criteria will receive first-line Ivonescimab monotherapy until disease progression or unacceptable toxicity occurs. The recommended dosage of Ivonescimab is 20 mg/kg administered intravenously every 3 weeks. Each infusion should be completed over 60 minutes (± 10 minutes). For patients who cannot tolerate the 60-minute (± 10 minutes) infusion, the duration may be extended to a maximum of 120 minutes (± 10 minutes). Dosing may be interrupted or permanently discontinued based on individual patient safety and tolerability; however, dose increases or reductions are not recommended. Dose modification and management of adverse events will follow the drug label and relevant guidelines. Any other concomitant supportive care or medications during the study period should be based on a comprehensive patient assessment, excluding contraindications explicitly stated in the label or guidelines, and administered according to the routine clinical practice of each center.

Assessment Plan: The timing, items, and frequency of all assessments, including tumor imaging evaluations and laboratory tests, will follow the routine clinical practice of each participating center.

Study Procedures: This study does not mandate protocol-defined study visits. A suggested visit schedule is provided solely to facilitate unified data collection and management.

Investigators will prospectively and continuously collect clinical data for all patients who provide signed informed consent and meet the eligibility criteria via an Electronic Data Capture (EDC) system until a study endpoint event occurs or the study concludes.

Inclusion Criteria

1. Voluntary participation in the study and provision of written informed consent approved by the Institutional Review Board (IRB)/Independent Ethics Committee (IEC).
2. Age ≥ 18 years at enrollment, male or female.
3. Histologically or cytologically confirmed locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) non-small cell lung cancer (NSCLC) according to the International Association for the Study of Lung Cancer (IASLC) 9th edition TNM classification, and judged by the investigator as not amenable to curative surgery or definitive concurrent chemoradiotherapy.
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2.
5. Life expectancy ≥ 3 months.
6. Tumor tissue PD-L1 expression positive, defined as tumor proportion score (TPS) ≥ 1% (any antibody clone), as determined by a central laboratory or a qualified pathology department accredited by the study site. If PD-L1 status has not been previously tested, the subject must provide tumor tissue samples (archived or freshly obtained) obtained at or after the diagnosis of locally advanced or metastatic disease, approximately 10-15 unstained slides, for PD-L1 testing.
7. Subjects with actionable driver alterations including EGFR exon 21 insertions, c-MET aberrations (amplification/overexpression/exon 14 skipping mutation), BRAF V600E, HER2, KRAS G12C, etc., for whom immunotherapy remains a primary/optional/standard first-line treatment, and who are assessed by the investigator as likely to benefit from ivonescimab, are permitted to enroll. For subjects with non-squamous histology, testing for actionable driver mutations must be performed prior to enrollment. For subjects with squamous histology, testing is recommended; if not performed, enrollment may proceed based on clinical judgment (e.g., male smokers may be exempted from testing).
8. No prior systemic anticancer therapy for locally advanced or metastatic NSCLC. Subjects who have received neoadjuvant/adjuvant therapy with curative intent are eligible if the time from last treatment to recurrence/metastasis is > 6 months.
9. At least one measurable lesion at baseline per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
10. The treating physician has decided to initiate first-line therapy with ivonescimab monotherapy for this subject.
11. Adequate organ function and reserve to tolerate the study treatment, as judged by the investigator based on clinical practice.
12. Urine dipstick protein ≤ 1+ is eligible; if ≥ 2+, a 24-hour urine protein quantification must be performed and the result must be ≤ 1 g/24h for enrollment.
13. Non-sterilized male subjects and female subjects of childbearing potential must agree to use effective contraceptive measures from the screening period until at least 120 days after the last dose of study treatment.

Exclusion Criteria

1. Histological diagnosis containing small cell carcinoma or neuroendocrine carcinoma components.
2. Currently participating in another interventional clinical study.
3. Known actionable driver alterations in *EGFR*, *ALK*, *ROS1*, *RET*, or other driver genes for which first-line approved therapies are available.
4. History of severe bleeding tendency or coagulation disorders; clinically significant bleeding symptoms within 1 month before the first dose, including but not limited to gastrointestinal bleeding, hemoptysis (defined as coughing up or expelling ≥ 1 teaspoon of fresh blood or small blood clots, or expectorating only blood without sputum; subjects with blood-streaked sputum are eligible), or nasal bleeding (excluding epistaxis and blood-tinged postnasal drip).
5. Radiologically confirmed tumor invasion of major blood vessels (e.g., aorta, central arteries/veins), vital organs (heart, trachea, esophagus, main bronchus), or encasement of major vessels with luminal stenosis. Presence of risk of esophagotracheal/pleural fistula; or pulmonary lesions with cavitation/necrosis assessed as having a life-threatening bleeding risk.
6. Prior treatment with systemic immunotherapy targeting tumor immune evasion mechanisms, including immune checkpoint inhibitors (e.g., PD-1/PD-L1, CTLA-4, TIGIT, or LAG3 inhibitors) or immune checkpoint agonists (e.g., CD40, CD137, ICOS, OX40, GITR antibodies), or cellular immunotherapy; or prior treatment with systemic anti-angiogenic therapy (including but not limited to bevacizumab and its biosimilars, ramucirumab, endostatin, apatinib, anlotinib, etc.).
7. Active central nervous system (CNS) metastatic lesions that have not shown significant symptom improvement after targeted therapy (e.g., surgery, radiotherapy). Untreated asymptomatic brain metastases (i.e., no neurological symptoms, no requirement for corticosteroid therapy, and no significant perilesional edema) are allowed.
8. Presence of brainstem, leptomeningeal, spinal cord metastases, or spinal cord compression.
9. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis; or evidence of active pneumonitis on chest CT during screening; or acute exacerbation of chronic obstructive pulmonary disease within 1 month before the first dose. Subjects with a history of radiation pneumonitis (which has become fibrotic) are allowed.
10. Occurrence of any of the following within 6 months before the first dose: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass grafting, congestive heart failure (New York Heart Association [NYHA] Class ≥ II), cerebrovascular accident (stroke), transient ischemic attack (TIA), or arterial/venous thromboembolic events of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade ≥ 3 (e.g., pulmonary embolism, deep vein thrombosis, except asymptomatic catheter-related thrombosis); presence of severe arrhythmias requiring treatment (e.g., atrial fibrillation, supraventricular tachycardia, etc.), QTc interval prolongation (male > 450 ms, female > 470 ms), or poorly controlled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg); or history of hypertensive crisis or hypertensive encephalopathy.
11. History of immunodeficiency; positive test for HIV antibody; currently receiving long-term systemic corticosteroid therapy.
12. Known active tuberculosis (TB); subjects suspected of active TB must undergo clinical examination to rule it out; known active syphilis infection.
13. History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
14. Severe infection within 4 weeks before the first dose, including but not limited to comorbidities requiring hospitalization, sepsis, or severe pneumonia.
15. Major surgery or severe trauma within 30 days before the first dose, or planned major surgery within 30 days after the first dose (as judged by the investigator); minor local surgery (excluding peripherally inserted central catheter [PICC] and venous port implantation) within 7 days before the first dose.
16. Known history of severe (Grade ≥ 3) hypersensitivity reaction to ivonescimab, any of its excipients, or other monoclonal antibodies.
17. Any severe psychiatric or social condition that, in the investigator's judgment, may interfere with study compliance or data reliability.
18. Concomitant diseases or medications that, in the investigator's judgment, may affect treatment compliance or patient safety during the study period.
19. Pregnant or breastfeeding women.
20. Any other condition deemed by the investigator as inappropriate for enrollment.

This study population consists of adult patients with locally advanced or metastatic, driver gene-negative, PD-L1-positive non-small cell lung cancer (NSCLC) who initiate ivonescimab monotherapy as first-line systemic treatment in routine clinical practice. Eligible patients will be consecutively identified and enrolled from multiple participating centers in China. Clinical, pathological, and imaging data will be collected from medical records and follow-up visits to describe real-world effectiveness and safety outcomes associated with ivonescimab treatment in this setting.

De-identified individual participant data (IPD) underlying the primary and key secondary endpoints, as well as the study protocol and statistical analysis plan, may be shared with qualified researchers upon reasonable request after publication of the main study results. Data will be shared following approval of a methodologically sound proposal and completion of a data use agreement, in accordance with applicable laws and institutional policies.

De-identified IPD and supporting documents will be available after publication of the primary results of this study or regulatory submission (whichever occurs first), and after review and approval of a data sharing request by the sponsor and/or principal investigators. Data are planned to be available for at least 5 years from the date of the primary publication, or longer if considered scientifically appropriate and feasible.

Access to de-identified IPD and supporting documents will be provided to qualified researchers affiliated with academic or public research institutions who submit a scientifically sound and ethically appropriate research proposal. Requests should include a detailed analysis plan and will be reviewed by the sponsor and/or a designated review committee. Upon approval, requestors will be required to sign a data use agreement that defines the scope of use, data protection measures, and publication requirements. Data will be shared through a secure data transfer method or controlled-access platform in accordance with applicable laws, institutional policies, and ethics committee requirements in China.