Bronchoscopic Cryoablation Combined With Chemo-Immunotherapy in NSCLC With Central Airway Obstruction

Inclusion Criteria:

* Understand the requirements and contents of the clinical trial and provide a signed and dated informed consent form.
* Age≥18 years and≤80 years.
* Histologically or cytologically confirmed and documented locally advanced or metastatic non-small cell lung cancer (NSCLC) without prior systemic therapy and EGFR-sensitive mutations (19del, L858R and T790M).
* Presence of a palliative treatment lesion in the central airway that is amenable to ablation, endoscopically assessed to be≥1/3 obstruction, such as primary or metastatic malignancy to the trachea, main bronchi, intermediate bronchi, or segmental bronchi. corresponding respiratory symptoms or obstructive pneumonia is permission to be included.
* Eastern Cooperative Oncology Group (ECOG) ： 0-2.
* Predicted survival ≥ 12 weeks.
* Adequate bone marrow hematopoiesis and organ function (cardiac function, hepatic, and renal function).
* Presence of measurable lesions according to RECIST 1.1 criteria.
* Subjects with stable brain metastases may be included in the study.

Exclusion Criteria:

* Histological diagnosis of small cell, large cell lung cancer; mixed tumors will be classified based on the primary cell type; if the primary component is small cell, large cell, or neuroendocrine carcinoma, the subject will not be eligible for enrollment; however, mixed adenocarcinoma-squamous cell carcinoma is acceptable. Subjects with driver gene mutations are generally not eligible for enrollment.
* Malignant central airway obstruction with acute dyspnea or severe life-threatening symptoms of malignant airway stenosis, or assessed by the investigator to be unable to tolerate subsequent treatment; extrinsic airway compression; large pleural effusion, severe coughing, massive hemoptysis, dyspnea, or inability to cooperate; severely impaired lung function with a maximal voluntary ventilation (MVV) \< 39% or inability to ambulate.
* Prior systemic therapy for locally or metastatic disease.
* Uncorrectable coagulation disorders, severe bleeding tendencies, platelet count \< 50 \*10\^9/L, or severe coagulation dysfunction.
* Presence of symptomatic brain metastases.
* Known severe hypersensitivity to anti-PD-1 monoclonal antibodies or similar drugs (allergic reactions with CTCAE≥ grade 3 toxicity).
* Subjects with persistent or active infection, including but not limited to hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV).
* Any concurrent malignancy other than basal cell carcinoma or cervical carcinoma in situ. (Patients with a history of malignant tumors but with no evidence of disease for≥ 3 years may be included ).
* Women who are breastfeeding or pregnant.
* Other conditions assessed by the investigator to be unsuitable for participation in the study.