• Eligible subjects selected for this study must meet all of the following criteria:

∙ Sign written informed consent before implementing any trial-related procedures;

‣ Age ≥18 years old and ≤75 years old;

‣ No limit on the gender;

‣ Cohort A: histological or cytological confirmed locally advanced (IIIB-IIIC) or metastatic (stage IV) NSCLC (International Association for the Study of Lung Cancer and Joint Committee on the American Classification of Cancer, TNM Lung cancer stage 8) without EGFR gene sensitive mutations, ALK gene fusion or ROS1 gene fusion confirmed by histological specimens, Relapse after failure of first-line anti-PD-1 /PD-L1 antibody therapy, as follows:

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∙ Only one anti-PD-1/PD-L1 antibody monotherapy or combination therapy is accepted in the advanced stage of the disease, and other immunotherapy is not allowed;

‣ Previous anti-PD-1/L1 antibody monotherapy or combination therapy has the best curative effect (according to RECIST 1.1 criteria) as partial remission, complete remission, or stable disease for ≥6 months (defined as within 6 months from the first medication) No disease progression has occurred);

‣ Disease progression confirmed by imaging studies occurred during or after the most recent treatment.

• Cohort B: histological or cytological confirmed locally advanced (IIIB-IIIC) or metastatic (stage IV) NSCLC (International Association for the Study of Lung Cancer and Joint Committee on the American Classification of Cancer, TNM Lung cancer stage 8) with histologically confirmed EGFR-sensitive mutations or ALK fusion, Relapse after failure of anti-EGFR-TKI or ALK-TKI therapy, as follows:

• In patients with EGFR-tKI sensitive mutations, the specific history of previous EGFR-TKI treatment can be one of the following:

⁃ There is no T790M mutation in 20 exon after the failure of previous one or two generations of EGFR-TKI (including gefitinib, erlotinib, icotinib and afatinib);

⁃ The 20 exon T790M mutation occurred after the treatment failure of the first or second generation EGFR-TKI monotherapy (including gefitinib, erlotinib, icotinib, and afatinib, etc.), and disease progression recurred after treatment with osimertinib or other third generation EGFR-TKI;

⁃ Failure of prior osimertinib or other third-generation EGFR-TKI therapy as first-line therapy (regardless of EGFR T790M mutation status);

⁃ Those who are allowed to receive neoadjuvant/adjuvant targeted therapy in the early stage and develop drug resistance after subsequent adjuvant targeted therapy, and their drug resistance status meets one of the three requirements of appeal.

⁃ For patients with ALK fusion NSCLC, disease progression should occur after adequate ALK-TKI treatment, and there is no opportunity for subsequent targeted therapy.

⁃ Cohort C: Locally advanced NSCLC that is not suitable for radical surgery or radiotherapy, or that has relapsed without systematic treatment, or that has metastasized without systematic treatment and is negative for PD-L1 expression. Patients who have previously received neoadjuvant or adjuvant therapy can also receive neoadjuvant or adjuvant therapy (but neoadjuvant or adjuvant therapy is chemotherapy/radiotherapy, not immunotherapy), and the end of neoadjuvant/adjuvant therapy should be ≥6 months after tumor progression; If the pathological type is adenocarcinoma, the absence of EGFR-sensitive mutations or ALK fusion or ROS1 fusion should be confirmed. Negative expression of PD-L1 was defined as TPS \<1% using 22C3 test.

• 5\. According to the evaluation criteria for the efficacy of solid tumors (RECIST v1.1 version), there is at least one imaging measurable lesion. The lesions located in the radiation field of the previous radiotherapy can be regarded as measurable lesions if the progress is confirmed; 6. Subjects with brain metastases asymptomatic or with stable symptoms after local treatment are allowed to be included in the group, as long as the subjects meet the following conditions:

⁃ There are measurable lesions outside the central nervous system;

⁃ no symptoms of the central nervous system or no worsening of symptoms within at least 2 weeks;

⁃ No need for glucocorticoid therapy, or stop glucocorticoid therapy within 7 days before the first administration, or the dosage of glucocorticoid is stable and reduced to less than 10mg/day prednisone (or equivalent dose) within 7 days before the first administration ; 7. Subjects are allowed to receive palliative radiotherapy (including craniocerebral radiotherapy for symptomatic brain metastases), but the radiotherapy must be completed at least 1 week before enrollment, and the radiotherapy-related toxicity should be restored to less than or equal to 1 degree (CTCAE 5.0, except for hair loss).

• 8\. ECOG score 0-1 points; 9. Expected survival time\> 3 months; 10. Sufficient organ function, subjects need to meet the following laboratory indicators:

⁃ The absolute value of neutrophils (ANC) ≥1.5x109/L when no granulocyte colony-stimulating factor is used in the past 14 days;

⁃ In the case of no blood transfusion in the past 14 days, platelets ≥100×109/L;

⁃ In the past 14 days without blood transfusion or erythropoietin, hemoglobin\>9g/dL;

⁃ Total bilirubin≤1.5×upper limit of normal (ULN);

⁃ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) within ≤2.5×ULN (subjects with liver metastases are allowed to have ALT or AST ≤5×ULN);

⁃ Serum creatinine ≤1.5×ULN and creatinine clearance rate (calculated by Cockcroft-Gault formula) ≥50ml/min;

⁃ Good coagulation function, defined as International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 times ULN;

⁃ Normal thyroid function is defined as thyroid-stimulating hormone (TSH) within the normal range. If the baseline TSH is out of the normal range, subjects whose total T3 (or FT3) and FT4 are within the normal range can also be included in the group;

⁃ Myocardial enzyme spectrum is within the normal range (for example, simple laboratory abnormalities that are judged by the investigator to be of no clinical significance are also allowed to be included in the group); 11. For female subjects of childbearing age, a urine or serum pregnancy test and the result should be negative within 3 days before receiving the first study drug administration (day 1 of cycle 1). If the urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is required. Women of non-bearing age are defined as at least 1 year after menopause, or have undergone surgical sterilization or hysterectomy; 12. If there is a risk of conception, all subjects (whether male or female) need to adopt a low annual failure rate during the entire treatment period until 120 days after the last study drug administration (or 180 days after the last study drug administration) Less than 1% of contraceptive measures; 13. Blood pressure can be adequately controlled with or without anti hypertensive medication, defined as blood pressure≤150/ 90 mm Hg, and blood pressure was under stable control within 1 week before randomization.

• 14\. Patients must have recovered from toxicity or complications if they have previously received surgery or radiation \> 30Gy.