The Efficacy and Safety of the Combination of PD-1 With Chemotherapy and Adaptive Radiotherapy Strategy in the Treatment of Stage III Non-small Cell Lung Cancer Patients

Inclusion criteria

• The subjects are willing and able to comply with the scheduled visits, treatment plans, laboratory tests, and other requirements of the study
• Age range of 18-75 years old upon enrollment, both male and female are eligible
• Stage III NSCLC confirmed by histology or cytology (according to the International Union Against Cancer and the Joint American Committee on Cancer 8th edition TNM staging of lung cancer)
• It was clarified that surgical resection is not possible After MDT discussion,
• The main driver genes have no sensitive mutations (including EGFR, ALK, ROS1, MET, HER2, etc.)
• No previous systematic anti-tumor treatment or chest radiotherapy for NSCLC
• According to RECIST v1.1, there is at least one measurable lesion, and according to RECIST v1.1, this lesion is suitable for repeated and accurate measurements
• There is sufficient organ function reserve to meet the needs of clinical research

Exclusion criteria

• There are any small cell carcinoma components present in the histopathology, as well as special types such as salivary gland type and SMARCA4 deficiency
• Except for NSCLC, the subjects had other malignant tumors within the 5 years prior to enrollment. Subjects with other tumors that have been cured by local treatment, such as basal or cutaneous squamous cell carcinoma, superficial bladder cancer, cervical or breast cancer in situ, are not excluded
• Previously received local treatments for tumor lesions such as thoracic radiotherapy and radiofrequency ablation
• Received non-specific immunomodulatory therapy (such as interleukin, interferon, thymosin, tumor necrosis factor, etc., excluding IL-11 used to treat thrombocytopenia) within 2 weeks before the first administration; Received Chinese herbal medicine or traditional Chinese patent medicines and simple preparations with anti-tumor indications within 1 week before the first administration
• Suffering from active autoimmune diseases that require systematic treatment within the past two years
• History of immunodeficiency; Individuals who test positive for HIV antibodies; Currently in long-term use of systemic corticosteroids or other immunosuppressants
• Subjects who are known to have active pulmonary tuberculosis (TB) and suspected of having TB need to undergo clinical examination to exclude them; Known active syphilis infection
• Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation
• Previous or current non infectious pneumonia/interstitial lung disease requiring systemic corticosteroid therapy
• Serious infection occurred within 4 weeks prior to the first administration, including but not limited to comorbidities requiring hospitalization, sepsis, or severe pneumonia; Active infections that have received systemic anti infective therapy within 2 weeks prior to the first administration (excluding antiviral therapy for hepatitis B or C)
• Current active hepatitis B subjects (HBsAg positive and HBV-DNA exceeding 1000 copies/ml (200IU/ml) or above the detection limit)
• Tumor invasion or compression of important surrounding organs (such as aorta, heart and pericardium, superior vena cava, trachea, esophagus, etc.) or the risk of developing esophagotracheal fistula or esophageal pleural fistula; Tumor mediastinal lymph node metastasis invading the trachea and main bronchus with the risk of bronchial fistula
• History of myocarditis, cardiomyopathy, and malignant arrhythmia in the past
• Within 6 months prior to the first administration, there is a history of esophageal and gastric varices, severe ulcers, unhealed wounds, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess, or acute gastrointestinal bleeding
• Any arterial thromboembolic event, NCI CTCAE 5.0 grade 3 or higher venous thromboembolic event, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy occurred within 6 months prior to the first administration; Currently, there is hypertension and after treatment with oral antihypertensive drugs, the systolic blood pressure is ≥ 160mmHg or the diastolic blood pressure is ≥ 100mmHg
• History of severe bleeding tendency or coagulation dysfunction
• Received a live vaccine within 30 days prior to the first administration, or planned to receive a live vaccine during the study period
• Known to be allergic to any component of any anti-tumor drug; Known history of severe hypersensitivity reactions to other monoclonal antibodies
• Known history of mental illness, drug abuse, alcoholism, or drug use
• Pregnant or lactating women
• Any past or current diseases, treatments, or laboratory abnormalities that may confuse the research results, affect the participants' full participation in the study, or may not be in the best interests of the participants
• Local or systemic diseases caused by non malignant tumors, or diseases or symptoms secondary to tumors, which can lead to higher medical risks and/or uncertainty in survival evaluation, such as tumor like leukemia reactions (white blood cell count\>20 × 109/L), cachexia manifestations (such as known weight loss of more than 10% in the first 3 months of screening), etc