Effect of Time-of-Day (ToD) for Immunochemotherapy on PFS in NSCLC

Inclusion Criteria:

1. Understand the requirements and contents of the clinical trial, and provide a signedand dated informed consent form.

2. Age ≥ 18 years.

3. Histopathology or cytology confirmed and recorded local progression or metastaticnon-small cell lung cancer without systemic treatment.

4. EGFR, ALK and ROS1 mutations negative confirmed by an accredited local laboratory.

5. ECOG 0-1.

6. Predicted survival ≥ 12 weeks.

7. Adequate bone marrow hematopoiesis and organ function

8. Presence of measurable lesions according to RECIST 1.1.

9. Subjects with stable brain metastases may be included in the study.

Exclusion Criteria:

1. Prior systemic therapy for locally advanced or metastatic disease.

2. Subjects who have received any of the following treatments must be excluded:

• Ant Treatment with chemotherapy or molecules such as EGFR, VEGFR antibodieswithin 4 weeks prior to the first dose of study drug.

• Have received radiation within 14 days prior to the first dose or have notrecovered from radiation-related toxicity. Chest and extra-brain palliativeradiotherapy, stereotactic radiosurgery, and stereotactic body radiotherapy maybe performed 7 days prior to the first dose.

3. Presence of spinal cord compression or meningeal metastasis.

4. History of other malignant tumors within 2 years.

5. Adverse events (except alopecia of any degree) of CTCAE > grade 1 due to priortreatment (e.g., adjuvant chemotherapy, radiotherapy, etc.) prior to the first dose.

6. History of stroke or intracranial hemorrhage within 6 months prior to the firstdose.

7. The presence of any severe or poorly controlled systemic disease, including poorlycontrolled hypertension and active bleeding in the judgment of the investigator.

8. Subjects with persistent or active infection, including but not limited to hepatitisB (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV) and COVID-19infection.

9. Heart-related diseases or abnormalities

10. Past history of interstitial lung disease, drug-induced interstitial lung disease,radiation pneumonitis requiring steroid therapy or interstitial lung disease withactive clinical symptoms, immune pneumonia caused by immunotherapy.

11. Refractory nausea and vomiting, chronic gastrointestinal disease, difficultyswallowing drugs, or inability to adequately absorb sunvozertinib or anlotinib dueto previous bowel resection.

12. Live vaccine was given 2 weeks before the first medication.

13. Women who are breastfeeding or pregnant.

14. Hypersensitivity to the test drug and the ingredients.

15. Other conditions assessed by the investigator to be unsuitable for participation inthe study.