Phase Ib: To observe the safety and tolerability of the combination of SI-B001 and SI-B003, and to determine the recommended dose of phase II clinical study (RP2D) in the indication of locally advanced or metastatic non-small cell lung cancer. Phase II: To evaluate the efficacy of SI-B001+SI-B003 combination with or without chemotherapy in patients with locally advanced or metastatic non-small cell lung cancer.

Inclusion Criteria:

1. Voluntarily sign the informed consent form and comply with the protocol requirements;
2. No gender restrictions;
3. Age ≥18 years and ≤75 years;
4. Expected survival time ≥3 months;
5. Subjects must agree to complete ctDNA testing during the screening period;
6. Histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) patients;
7. Agree to provide archived or fresh tumor tissue samples from primary or metastatic lesions;
8. Must have at least one measurable lesion as defined by RECIST v1.1;
9. Performance status score: ECOG ≤1;
10. Toxicity from prior anti-tumor therapy has recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0;
11. No severe cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥50%;
12. Organ function levels must meet the requirements without transfusion, albumin, colony-stimulating factors, any cell growth factors, and/or platelet-raising drugs within 14 days before the first dose of the study drug;
13. Coagulation function: International Normalized Ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5 × ULN;
14. Urine protein ≤1+ or ≤1000 mg/24h;
15. Female subjects of childbearing potential or male subjects with partners of childbearing potential must use highly effective contraception from 7 days before the first dose until 24 weeks after the last dose. Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days before the first dose.

Exclusion Criteria:

1. Prior to signing the informed consent form, relevant genetic alterations were indicated;
2. For patients enrolled in Phase II, any of the following conditions apply: a) Patients suitable for and willing to undergo local therapy; b) Patients who have received systemic chemotherapy;
3. Symptomatic brain parenchymal or leptomeningeal metastases, deemed ineligible by the investigator;
4. Participation in any other clinical trial within 4 weeks prior to the administration of this trial's investigational product (based on the last dose date);
5. Use of chemotherapy, biologic therapy, immunotherapy, etc., within 4 weeks or 5 half-lives prior to the first dose, or palliative radiotherapy, small-molecule targeted therapy, or other antitumor treatments within 2 weeks before the first dose;
6. Major surgery (as defined by the investigator) within 4 weeks prior to the first dose;
7. Requirement for systemic corticosteroids or immunosuppressive therapy within 2 weeks before the study drug administration;
8. Pulmonary diseases graded as ≥3 according to NCI-CTCAE v5.0; history of interstitial lung disease (ILD), current ILD, or suspected ILD during screening;
9. Concurrent pulmonary disease resulting in clinically significant respiratory impairment;
10. Unstable thrombotic events requiring therapeutic intervention within 6 months before screening (excluding catheter-related thrombosis);
11. Active infection requiring intravenous anti-infective therapy;
12. Imaging findings indicating tumor invasion or encasement of major thoracic, cervical, or pharyngeal blood vessels, with a risk of bleeding post antitumor therapy;
13. Prior immunotherapy leading to ≥Grade 3 immune-related adverse events (irAE) or ≥Grade 2 immune-related myocarditis;
14. Use of live attenuated vaccines within 4 weeks before the first dose of the study drug;
15. Use of immunomodulatory drugs within 14 days before the first dose of the study drug;
16. Patients at risk of active autoimmune diseases or with a history of autoimmune diseases;
17. History of other malignancies within 5 years before the first dose;
18. Positive for human immunodeficiency virus (HIV) antibodies, active tuberculosis, active hepatitis B virus (HBV) infection, or hepatitis C virus (HCV) infection;
19. Poorly controlled hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg);
20. History of severe cardiovascular or cerebrovascular diseases;
21. Patients with significant serous cavity effusion, symptomatic effusion, or poorly controlled effusion;
22. History of allogeneic stem cell, bone marrow, or organ transplantation;
23. History of hypersensitivity to recombinant humanized antibodies or any excipients of SI-B001 or SI-B003;
24. History of autologous or allogeneic stem cell transplantation;
25. Pregnant or lactating women;
26. Any other condition deemed unsuitable for participation in this clinical trial by the investigator.