This study is aimed at patients with unresectable NSCLC who take nintedanib during sequential radiotherapy to explore the incidence of radiation pneumonitis above grade 2 in the nintedanib combined with radiotherapy mode and observe safety. And will further explore the progression-free survival (PFS) and overall survival (OS) of patients treated with nintedanib in combination with radiotherapy and immunotherapy.

Primary objective: To evaluate the safety of nintedanib combined with sequential radiotherapy in patients with unresectable NSCLC and the incidence of radiation pneumonitis above grade 2. Secondary objective: To evaluate the changes in lung function, progression-free survival (PFS) and overall survival (OS) in patients with unresectable NSCLC after nintedanib combined with sequential radiotherapy.

Patients need to receive induction therapy, chemotherapy and/or immunotherapy for at least one cycle. Then they will receive sequential radiotherapy and nintedanib for 6 months. Finally, they will receive immunotherapy maintenance therapy for 16 cycles.

Inclusion Criteria:

• 1) Men or women who are over 18 years old (including 18 years old) when signing the informed consent form;
• 2) Non-small cell lung cancer was confirmed by histology and could not be resected, and EGFR/ALK driver gene was confirmed negative by gene mutation examination;
• 3) At least one measurable lesion with imaging examination (according to RECIST1.1) is examined by spiral CT or MR, and the length and diameter of the lesion are ≥ 10 mm;
• 4) within 3 days before treatment, the score according to ECOG is 0 ~ 1;
• 5) Life expectancy ≥3 months;
• 6)The vital organs function well,
• 7)The subjects volunteered to join the study and signed the informed consent form, with good compliance and cooperation with the follow-up.

Exclusion Criteria:

• 1) Complicated with severe respiratory diseases: pulmonary fibrosis, active tuberculosis, etc.
• 2)Persons with mental disorder, blood system diseases, autoimmune diseases and serious primary diseases of heart, brain, liver and kidney;
• 3) Hemorrhagic events that require blood transfusion, invasive intervention or hospitalization occur within 3 months before the first administration, or there are bleeding symptoms and need intervention treatment (such as hemoptysis, hematuria and bloody stool), or high-risk factors with bleeding risk (such as tumor surrounding or invading important blood vessels, obvious necrosis or cavity around tumor, esophageal varices, etc.);
• 4) Thrombosis or embolic diseases, abnormal blood coagulation function and bleeding tendency;
• 5) Known or suspected to be allergic to the study drug and its auxiliary materials;
• 6) The baseline pregnancy test of pregnant and lactating women or fertile women is positive.
• 7) According to the researcher's judgment, the subjects have other factors that may lead to the forced termination of this study.

men or women over the age of 18 (including 18 years old), whose vital organs function well, who are diagnosed as non-small cell lung cancer by histology and cannot be surgically removed, and whose EGFR/ALK driver gene is negative by gene mutation test. The score of physical fitness in the Eastern Cooperative Oncology Group (ECOG) is 0 ~ 1, and the life expectancy is ≥3 months. At least one measurable lesion (non-brain) according to RECISTv1.1.