The purpose of this study is to assess the safety, tolerability and preliminary antitumor activity of SKB264 in combination with KL-A167 with or without chemotherapy with advanced or metastatic non-small cell lung cancer. The study is divided into two parts. Part 1 will be the safety run-in phase, and Part 2 will be the cohort expansion phase.

Inclusion Criteria:

1. Males or females ≥ 18 and ≤ 75 years of age at the time of signing the informed consent form;
2. Histologically and cytologically confirmed NSCLC;
3. Cohort 1: Patients with locally advanced/metastatic NSCLC with wild-type EGFR and negative ALK fusion gene, no or at most one prior line of systemic chemotherapy regimen for advanced or metastatic NSCLC. Cohort 2: Patients with locally advanced/metastatic NSCLC with wild-type EGFR and negative ALK fusion gene, no prior systemic therapy. Cohort 3: Patients with locally advanced/metastatic NSCLC with EGFR activating mutation and negative ALK fusion gene, who have failed previous treatment with EGFR-TKIs.
4. Provide fresh or archival tumor tissue for biomarker testing and analysis;
5. Patients with at least one measurable lesion per RECIST v1.1 criteria, and patients with only skin or bone lesions cannot be enrolled;
6. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 with an expected survival of ≥ 12 weeks;
7. Adequate organ and bone marrow function
8. For female patients of childbearing age and male patients with partners of childbearing age, they must use effective medical contraception during the study treatment period and for 6 months after the last dose of study medication (see Annex for specific contraceptive measures);
9. Each patient must voluntarily agree to participate in the study, sign the informed consent form, and comply with the protocol-specified visits and relevant procedures.

Exclusion Criteria:

1. Presence of small cell lung carcinoma (SCLC) components in histological pathology;
2. History of other malignancies;
3. Presence of metastases to brainstem, meninges and spinal cord, or spinal cord compression;
4. Presence of active central nervous system (CNS) metastases;
5. Imaging (CT or MRI) shows that the tumor surrounds important blood vessels, or the investigator determines that the tumor is most likely to invade important blood vessels during the subsequent study to cause fatal major hemorrhage;
6. Serious or uncontrolled cardiac disease or clinical symptoms requiring treatment, including any of the following:
7. Patients with (noninfectious) interstitial lung disease (ILD) or history of pneumonia requiring steroid therapy; patients with serious pulmonary function impairment due to lung disease;
8. Uncontrolled systemic disease as judged by the investigator, included uncontrolled hypertension, uncontrolled diabetes, pesence of pleural effusion, pericardial effusion, or ascites that is clinically symptomatic or requires repeated drainage;
9. Certain viral infections including active hepatitis B or hepatitis C; known history of positive human immunodeficiency virus (HIV) test or known acquired immunodeficiency syndrome (AIDS); or positive syphilis antibody test;
10. Known active tuberculosis;
11. Known hypersensitivity to the study drug or any of its components, or severe allergic reactions to other monoclonal antibodies;
12. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
13. Pregnant or lactating women;
14. Any patient whose condition deteriorates rapidly during the screening process prior to the first dose, such as severe changes in performance status, unstable pain requiring adjustment of analgesic therapy, etc
15. Other circumstances that, in the opinion of the investigator, are not appropriate for participation in this study.