This is a multi-center, open-label, phase I study to evaluate the safety, efficacy, pharmacokinetics (PK), and immunogenicity of HS-20122 combined therapy in subjects with locally advanced or metastatic non-small cell lung cancer (NSCLC).

This is a multi-center, open-label, phase I study to evaluate the safety, efficacy, pharmacokinetics (PK), and immunogenicity of HS-20122 combination therapy in subjects with locally advanced or metastatic non-small cell lung cancer (NSCLC). A dose exploration stage of each combination therapy will be conducted in subjects with advanced or metastatic NSCLC patients who experienced disease progression (PD) on or after prior treatments, to explore appropriate doses. In addition, an dose-expansion stage will be conducted in appropriate target populations based on the data obtained in the dose exploration stage to further explore the safe and efficacy.

Inclusion Criteria:

1. Locally advanced or metastastic NSCLC;
2. Received at least 1 line SoC,or treatment naïve;
3. With at least 1 target lesion according to RECIST 1.1.
4. Appropriate organ function
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1 and no deterioration within 2 weeks prior to the first dose.
6. Minimum expected survival longer than 12 weeks
7. Female subjects of childbearing potential are willing to take appropriate contraceptive measures and should not breastfeed from signing the informed consent form (ICF) through 6 months after the last dose; male subjects are willing to use barrier contraception (i.e., condom) from signing the ICF through 6 months after the last dose.
8. Voluntarily participate in this clinical trial, understand the study procedures, and be able to sign written informed consent form.

Exclusion Criteria:

1. Insufficient wash out duration of prior systemic anticancer therapy
2. Local radiotherapy within 2 weeks prior to first dose of investigational drug
3. Pleural/abdominal effusion requires clinical intervention
4. Major surgery within 4 weeks prior to first dose of investigational drug
5. History of drugs may prolong QT interval
6. Have any grade ≥ 2 residual toxicity according to Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) from prior anti-tumor therapy (except alopecia and residual neurotoxicity).
7. Presence of brain metastasis or carcinomatous meningtitis
8. History of other primary malignancies
9. Significant, uncontrolled, or active cardiovascular diseases
10. Severe or poorly controlled diabetes
11. Extremely obesity or emaciation
12. Clinically significant bleeding symptoms or obvious bleeding tendency within 1 month prior to the first dose
13. Severe arteriovenous thrombotic events (e.g., deep venous thrombosis, pulmonary embolism) within 3 months prior to the first dose
14. Severe infection within 4 weeks
15. History of systemic glucocorticoids over 28 days prior to first dose of investigational drug
16. Presence of known active infectious diseases,
17. Prensence of ophthalmological abnormalities.

17.Presence of hepatic encephalopathy, Hepato-renal Syndrome 18.Presence or history of confirmed or suspected ILD; 19.Prior history of significant neurological or mental disorders, including conditions that interfere with assessment, such as epilepsy, dementia, or major depressive disorder.

20.History of severe allergy, or history of hypersensitivity to any active or inactive ingredient of investigational drugs.

21.Presence of any conditions that jeopardize subject safety or interfere with study assessments as judged by the investigator.