The goal of this clinical trial is to compare the efficacy and safety of induction Benmelstobart plus Anlotinib and chemotherapy followed by concurrent chemoradiotherapy (CCRT) and subsequent Benmelstobart maintenance versus CCRT followed by Benmelstobart maintenance in patients with unresectable stage III NSCLC. Additionally, high-throughput sequencing and multi-omics analysis will be performed on patient-derived tissue and blood samples. By integrating baseline characteristics with clinical data, we aim to identify key determinants of treatment efficacy and prognosis, thereby establishing a precision evaluation system for therapeutic outcomes.

Inclusion Criteria:

• 1. Voluntary signing of a written ICF.
• 2. Age at enrollment: 18-75 years; both sexes are eligible.
• 3. Eastern Cooperative Oncology Group (ECOG) performance status score: 0 or 1.
• 4. Expected survival: ≥3 months.
• 5. Histologically or cytologically confirmed stage III NSCLC (classified according to the International Union Against Cancer and the American Joint Committee on Cancer's 9th edition of the lung cancer TNM staging system).
• 6. Definitively determined as unresectable after MDT discussion.
• 7. The primary driver genes must not harbor sensitive mutations (including EGFR (exon 19 deletion, exon 21 L858R point mutation, exon 20 insertion, etc.), ALK fusion, ROS1 fusion, MET exon 14 skipping mutation, HER2 exon 20 mutation, BRAF V600E mutation, RET fusion, NTRK fusion). For non-squamous NSCLC, a prior tissue-based common genetic testing report must be provided; otherwise, tumor tissue samples (archived or fresh, primary or metastatic) must be collected prior to enrollment for genetic mutation status assessment (at a local laboratory or central laboratory). For squamous NSCLC subjects with a smoking history or current smoking status, if the prior primary driver gene mutation status is unknown, no corresponding testing is required prior to enrollment, and the status shall be considered negative.
• 8. No prior systemic antitumor therapy or chest radiotherapy for NSCLC.
• 9. At least one measurable lesion according to RECIST v1.1, and such lesions must be suitable for repeated accurate measurement per RECIST v1.1 criteria. -10. Subjects must provide tumor tissue samples diagnosed as locally advanced tumors at the time of diagnosis or thereafter, including archived or freshly obtained uncolored formalin-fixed paraffin-embedded (FFPE) pathological sections (preferably recently obtained tumor tissue samples), approximately 10-25 sections (of which approximately 10-15 sections are required for EGFR and ALK testing, and approximately 10 sections for PD-L1 expression testing; however, additional sections must be provided if the central laboratory determines that the sample is insufficient for testing), or fresh tumor tissue specimens (frozen in liquid nitrogen for omics research). Tumor lesions used for fresh biopsy should not be designated as RECIST v1.1 target lesions unless the lesion is the only measurable lesion. For archived samples, collection must occur after the last systemic treatment, and the collection site must not have undergone radiotherapy. Note: If a subject's archived sample does not meet the above requirements, the investigator may determine that the biopsy does not serve the subject's best interests and may, after discussion with the project team, permit the use of the archived sample.
• 11.Fertile female subjects must have undergone a urine or serum pregnancy test within 7 days prior to the first medication administration (if the urine pregnancy test result is not negative, a serum pregnancy test must be performed, with the serum result serving as the definitive determination), and the result must be negative. If a fertile female subject has sexual intercourse with an unmarried male partner, she must have used an acceptable contraceptive method since the start of screening and must agree to continue using contraception for 120 days after the last administration of the antitumor drug; whether contraception should be discontinued after this period should be discussed with the investigator.
• 12. If an unmarried male subject has sexual intercourse with a fertile female partner, he must have used an effective contraceptive method from the start of screening until 120 days after the last administration; whether contraception should be discontinued after this time point should be discussed with the investigator.
• 13. The subject must be willing and able to comply with all scheduled visits, treatment regimens, laboratory tests, and other study requirements.

Exclusion Criteria:

• 1. Histopathological presence of any small cell carcinoma components, as well as specific types such as salivary gland type and SMARCA4 deletion.
• 2. Except for NSCLC, the subject had suffered from other malignancies within the preceding 5 years. Subjects who have been cured of other tumors through local treatment (e.g., basal or squamous cell carcinoma of the skin, superficial bladder cancer, cervical or breast carcinoma in situ) are not excluded.
• 3. Concurrent enrollment in another clinical study, unless it is an observational, non-interventional clinical study or a follow-up phase of an intervention study.
• 4. Previous local treatments targeting the tumor lesion, such as thoracic radiotherapy or radiofrequency ablation.
• 5. Receiving nonspecific immunomodulatory therapy (e.g., interleukins, interferons, thym peptides, tumor necrosis factor, etc., excluding IL-11 for thrombocytopenia) within 2 weeks prior to the first dose; or receiving herbal or proprietary Chinese medicines with antitumor indications within 1 week prior to the first dose.
• 6. Suffering from an active autoimmune disease requiring systemic treatment within the past two years (e.g., treatment with disease-modifying drugs, corticosteroids, or immunosuppressants). Alternative therapies (e.g., thyroxine, insulin, or physiological corticosteroid replacement for adrenal or pituitary insufficiency) are not considered systemic treatments.
• 7. History of immunodeficiency; positive HIV antibody test; or current long-term use of systemic corticosteroids or other immunosuppressants.
• 8. Subjects with known active tuberculosis (TB) or suspected active TB require clinical examination for exclusion; known active syphilis infection.
• 9. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• 10. Non-infectious pneumonia/interstitial lung disease requiring systemic glucocorticoid therapy within the past 5 years or currently.
• 11.Severe infections occurring within 4 weeks prior to the first dose, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia; active infections treated with systemic anti-infective therapy within 2 weeks prior to the first dose (excluding antiviral therapy for hepatitis B or hepatitis C).
• 12.Subjects with active Hepatitis B (Hepatitis B surface antigen [HBsAg] positive AND Hepatitis B virus DNA [HBVDNA] >1,000 copies/mL [200IU/mL] or above the lower limit of detection); note that HBsAg-positive subjects are required to receive antiviral therapy against Hepatitis B during the study treatment period. Subjects with active Hepatitis C (Hepatitis C virus [HCV] antibody positive AND HCV RNA levels above the lower limit of detection).
• 13Has undergone major surgical procedures or sustained severe trauma within 30 days prior to the first dose administration, or plans to undergo major surgery within 30 days after the first dose (as determined by the investigator); has undergone minor local surgeries within 3 days prior to the first dose administration (excluding peripheral venous catheterization and intravenous infusion port implantation).
• 14. The tumor invades or compresses surrounding vital organs (e.g., aorta, heart and pericardium, superior vena cava, trachea, esophagus) or carries a risk of esophageal-tracheal fistula or esophageal-plenic fistula; mediastinal lymph node metastasis involves the trachea or main bronchi with a risk of bronchial fistula.
• 15. Currently has uncontrolled comorbid conditions, including but not limited to decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, severe active peptic ulcer disease or gastritis, or psychiatric/social conditions that may limit the subject's adherence to study requirements or affect their capacity to provide written informed consent.
• 16. Has a history of myocarditis, cardiomyopathy, or malignant arrhythmias; experienced unstable angina, myocardial infarction, congestive heart failure, or vascular diseases (e.g., aneurysm with rupture risk) requiring hospitalization within 12 months prior to the first dose; or has other cardiac injuries that may affect the safety evaluation of antineoplastic agents.
• 17. History of esophageal and gastric varices, severe ulcers, non-healed wounds, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess, or acute gastrointestinal bleeding within 6 months prior to the first dose; or acute exacerbation of chronic obstructive pulmonary disease within 1 month prior to the first dose.
• 18. History of any arterial thromboembolic event, venous thromboembolic event of grade 3 or higher per NCI CTCAE 5.0 criteria, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 6 months prior to the first dose; or current hypertension with systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg despite oral antihypertensive therapy.
• 19.Patients with a history of severe bleeding tendency or coagulation disorders; those with clinically significant hemoptysis (defined as coughing up or expectorating ≥ 1 teaspoon of fresh blood or small blood clots or only blood without sputum, patients with blood in sputum are allowed to be enrolled) within 1 month before the first administration; those with imaging findings during the screening period showing that the tumor encircles important blood vessels or has obvious necrosis or cavities, and the investigator determines that participation in the study would pose a risk of bleeding.
• 20. Received a live vaccine within 30 days prior to the first dose, or plans to receive a live vaccine during the study period.
• 21. Known hypersensitivity to any component of any antineoplastic agent; history of severe hypersensitivity reactions to other monoclonal antibodies.
• 22. Known history of mental illness, drug abuse, alcoholism, or substance use.
• 23. Women who are pregnant or breastfeeding.
• 24. Any past or current medical conditions, treatments, or laboratory abnormalities that may confound study results, compromise the participant's ability to complete the study, or make participation potentially detrimental to the participant's best interests.
• 25. Localized or systemic diseases not caused by malignancies, or tumor-related conditions or symptoms, that may pose significant medical risks and/or uncertainty in survival assessment, such as tumor-associated leukemic response (white blood cell count>20 × 10⁹/L) or cachectic manifestations (e.g., known weight loss exceeding 10% within three months prior to screening).