Cadonilimab in Patients (Pts) with Advanced Non-small Cell Lung Cancer (NSCLC)

Inclusion Criteria:

1. Age≥18 years old

2. Locally advanced (stage IIIB/IIIC) that cannot be resected by radical surgery andcannot accept radical synchronous/sequential radiotherapy and chemotherapy andmetastatic (stage IV) non-squamous NSCLC confirmed by histology or cytology

3. Patients must have progressed on at most a PD-1/L1 inhibitor and a platinum-basedchemotherapy (combined or sequential, regardless of sequence), and at least twocycles of PD-1/L1 inhibitor (combined or non-combined chemotherapy) with clinicalbenefits (PFS ≥ 3 months)

4. Patients must not have EGFR sensitizing mutations, EGFR T790M mutation, ALK genefusion, and ROS 1 gene rearrangement, and BRAF V600E mutation.

5. Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Lesions situated in a previously irradiated area are consideredmeasurable if progression has been demonstrated in such lesions

6. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

7. Life expectancy > 12 weeks as determined by the investigator

8. Patients must have at least one measurable lesion (as defined by RECIST v1.1), whichis suitable for repeated and accurate measurement

9. Absolute neutrophil count (ANC) ≥ 1500/uL (collected within 10 days prior to thestart of study treatment)

10. Platelets ≥ 100 000/uL (collected within 10 days prior to the start of studytreatment)

11. Hemoglobin ≥ 9.0 g/dL (collected within 10 days prior to the start of studytreatment)

12. Creatinine clearance [CrCl]) ≥ 50 mL/min(Creatinine clearance (CrCl) should becalculated per institutional standard)

13. Total bilirubin ≤ 1.5 x ULN (collected within 10 days prior to the start of studytreatment)

14. Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x ULN (≤ 5 x ULN for participants with liver metastases) (collected within 10days prior to the start of study treatment

15. Serum albumin(ALB)≥28 g/L

16. International standardized ratio (INR) and activated partial thrombin time (APTT) ≤ 1.5 × ULN

17. Left ventricular ejection fraction (LVEF) ≥ 50%

18. A male participant must agree to use a contraception during the treatment periodplus an additional 120 days after the last dose of study treatment and refrain fromdonating sperm during this period

19. A female participant is eligible to participate if she is not pregnant, notbreastfeeding, and at least one of the following conditions applies:

20. Not a woman of childbearing potential (WOCBP) OR

21. A WOCBP who agrees to follow the contraceptive guidance during the treatmentperiod and for at least 120 days plus 30 days (a menstruation cycle) after thelast dose of study treatment

Exclusion Criteria:

1. Previously received treatment for tumor immune mechanism other than any anti-PD-1/L1inhibitor for advanced NSCLC stage, such asCTLA-4（CD152）、TIGIT、OX-40、CD137、ICOS、CD40、CD47、CD73、GITR、TOX、LAG-3、TIM3、SIRPα、BTLA（CD272）、VISTA（B7-H5）、LIGHT（CD258）、B7-H3（CD276）、 B7-H4（VTCN1）、HVEM、CD80/CD86、MHC Ⅱ、GAL9、IDO、PVR（CD155）、Nectin-2（CD112）.

2. Patients have prior exposure to docetaxel, bevacizumab

3. The last systemic anti-tumor treatment (chemotherapy, immunotherapy, biologicalagents, anti-angiogenic drugs, etc.) was received within 3 weeks before the firstadministration.

4. The following treatments were received within 2 weeks before the firstadministration: TKI treatment, hormone anti-tumor treatment, palliative localtreatment for non-target lesions Non-specific immunomodulatory therapy (such asinterleukin, interferon, thymosin, tumor necrosis factor, etc., excluding IL-11 forthrombocytopenia).

5. Patients with explosive progress.

6. Patients with other active malignant tumors except for NSCLC within 3 years beforeenrollment. Patients with other malignant tumors that have been cured by localtreatment, such as basal or cutaneous squamous cell carcinoma, superficial bladdercancer cancer, cervical or breast cancer in situ, are not excluded.

7. Patients with active autoimmune diseases that require systemic treatment in the pasttwo years (such as the use of disease improvement drugs, corticosteroids,immunosuppressants) (excluding irAE caused by the use of PD-1/L1 inhibitors).Replacement therapy (such as thyroid hormone, insulin, or physiologicalcorticosteroid replacement therapy for adrenal or pituitary insufficiency) is notconsidered as a systemic treatment.

8. Patients can not swallow pills, with malabsorption syndrome, or any condition thataffects gastrointestinal absorption;

9. Patients with active or previous history of inflammatory bowel disease (such asCrohn's disease, ulcerative colitis or chronic diarrhea).

10. Patients have a history of immune deficiency, with HIV antibody test positive or usesystemic corticosteroids or other immunosuppressants for a long time.