Becotatug Vedotin Combined With Pucotenlimab ± Radiotherapy as First-Line Treatment for Driver-Gene-Negative, EGFR-Expression-Positive Advanced Non-Small Cell Lung Cancer

Inclusion Criteria: 1. Voluntary participation with written informed consent obtained prior to any study-specific procedures, and willingness to comply with the study requirements. 2. Male or female patients aged between 18 and 75 years (inclusive) at the time of signing informed consent. 3. Histologically or cytologically confirmed Stage IV (M1a, M1b, or M1c according to the AJCC 8th Edition) squamous or non-squamous NSCLC. 4. No prior systemic therapy for advanced/metastatic disease is permitted. Patients who received adjuvant/neoadjuvant chemotherapy and relapsed ≥6 months after the last dose are allowed to enroll. 5. At baseline, presence of at least one measurable target lesion outside the primary tumor per RECIST v1.1, which is suitable for accurate repeated measurement and has not been previously irradiated or treated with other local therapies. 6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. 7. Absence of known actionable driver gene alterations (e.g., EGFR, ALK, ROS1) in both squamous and non-squamous NSCLC. All subjects (regardless of smoking history) must provide testing reports for EGFR, ALK, and ROS1. If no prior report exists, baseline biopsy or submission of archived tissue for assessment of driver gene status (via local or central laboratory) is mandatory. 8. Immunohistochemistry (IHC)-confirmed EGFR expression level of 2+ or higher. 9. Medically fit to tolerate radiotherapy, with an expected survival of ≥12 weeks. 10. No prior exposure to Antibody-Drug Conjugates (ADCs). 11. Adequate organ and bone marrow function as defined below (within 14 days prior to initiation of study treatment): \- Hematology (must not have received blood transfusions, granulocyte colony-stimulating factor \[G-CSF\], or hematopoietic growth factors within 14 days prior to screening): \- Hemoglobin (Hb) ≥ 90 g/L; \- Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L; \- Platelets (PLT) ≥ 75 × 10⁹/L. \- Blood Chemistry (must not have received albumin infusion within 14 days prior to screening): * Total Bilirubin (TBIL) ≤ 2.0 × ULN (≤ 3.0 × ULN for patients with Gilbert's syndrome); * Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 5.0 × ULN; * Serum Creatinine (Cr) ≤ 1.5 × ULN or Calculated Creatinine Clearance (CrCl) ≥ 50 mL/min (using the Cockcroft-Gault formula): Male: CrCl = ((140 - age) × weight) / (72 × serum creatinine) Female: CrCl = ((140 - age) × weight) / (72 × serum creatinine) × 0.85 (Note: Weight in kg; Serum creatinine in mg/dL) \- Coagulation Function: * International Normalized Ratio (INR) ≤ 2.0 or Prothrombin Time (PT) ≤ 6 seconds above the upper limit of normal. 12. Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to the first dose. If the urine test cannot be definitively confirmed as negative, a serum pregnancy test must be performed, and the serum result will be considered definitive. 13. Female subjects of childbearing potential who are sexually active with unsterilized male partners must agree to use highly effective contraception starting at screening and continue for 180 days after the last dose of study drug. 14. Sexually active male subjects who have not undergone sterilization and who are sexually active with female partners of childbearing potential must agree to use effective contraception starting at screening and continue for 180 days after the last dose. Decisions regarding the cessation of contraception beyond this timeframe should be discussed with the investigator. 15. Subjects must be willing and able to comply with scheduled visits, the treatment plan, laboratory tests, and other study requirements. Exclusion Criteria: 1\. Prior receipt of any systemic anti-tumor therapy for advanced, recurrent, or metastatic NSCLC, or perioperative therapy completed less than 6 months prior to enrollment. 2\. History of another malignancy within 5 years prior to enrollment (excluding cured basal cell carcinoma of the skin or carcinoma in situ of the cervix). Known hypersensitivity to Becotatug vedotin, Pucotenlimab, or any of their excipients. 3\. Prior treatment with any of the following: ADCs, PD-1/PD-L1 inhibitors, CTLA-4 inhibitors, or bispecific antibodies targeting immune checkpoints. 5\. History of severe bleeding tendency or coagulation dysfunction; significant clinically significant bleeding symptoms within 1 month prior to the first dose (including but not limited to gastrointestinal bleeding, hemoptysis \[defined as expectoration of ≥1 teaspoon of fresh blood or blood clots, or pure hemoptysis without sputum; subjects with blood-streaked sputum are allowed\]); nasal hemorrhage (excluding simple epistaxis and post-nasal drip with blood); imaging at screening showing tumor encasement of major vessels, significant tumor necrosis, or cavitation deemed by the investigator to pose a high bleeding risk; central or cavitary squamous NSCLC deemed high-risk for bleeding by the investigator; receipt of continuous antiplatelet or anticoagulant therapy within 10 days prior to the first dose. 6\. Tumor invasion of surrounding vital organs or vessels (e.g., aorta, heart and pericardium, superior vena cava, trachea, esophagus) or presence of risk factors for esophagotracheal fistula or esophagopleural fistula. 7\. Subjects with uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage (subjects not requiring drainage or requiring drainage less than once per month are allowed). 8\. Arteriovenous thromboembolic events within 6 months prior to randomization, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis (except those judged by the investigator to be fully resolved and related to venous catheters for prior chemotherapy), and pulmonary embolism. 9\. Symptomatic brain metastases. Subjects with brain metastases that have been treated and remain clinically stable for at least 1 month, and who have discontinued corticosteroids and anticonvulsants for at least 1 month prior to study entry, are allowed. 10\. Inability to provide documentation of driver gene-negative status or IHC evidence confirming EGFR expression ≥2+. Comorbidities/Medical History: 11\. Hypertension that cannot be adequately controlled with antihypertensive medication (systolic BP \>140 mmHg or diastolic BP \>90 mmHg); \- Within 6 months prior to randomization: myocardial infarction, severe/unstable angina, NYHA Class II or greater cardiac insufficiency, clinically significant supraventricular or ventricular arrhythmias, and symptomatic congestive heart failure; * Conditions significantly affecting oral drug absorption, such as inability to swallow, chronic diarrhea, or clinically significant intestinal obstruction; * Renal insufficiency: urinalysis indicating proteinuria ≥++, or confirmed 24-hour urine protein ≥1.0 g; * Human Immunodeficiency Virus (HIV) infection or known Acquired Immunodeficiency Syndrome (AIDS); active hepatitis (Hepatitis B defined as HBV-DNA ≥ 500 IU/mL; Hepatitis C defined as HCV-RNA above the lower limit of detection) or co-infection with Hepatitis B and C; * Presence of any active autoimmune disease or history thereof (including but not limited to autoimmune hepatitis, enteritis, vasculitis, nephritis; subjects requiring bronchodilator therapy for asthma are excluded); however, subjects with vitiligo, psoriasis, alopecia not requiring systemic treatment, or well-controlled Type 1 diabetes are allowed; * Severe infection within 4 weeks prior to the first dose, including but not limited to bacteremia or severe pneumonia requiring hospitalization; active infection requiring systemic antibiotics within 2 weeks prior to the first dose (CTCAE Grade ≥2); fever \>38.5°C of unknown origin during screening/prior to first dose (fever due to tumor progression judged by the investigator is allowed); evidence of active tuberculosis infection within 1 year prior to dosing. 12\. Major surgery within 28 days prior to the first dose (diagnostic tissue biopsy, PICC line placement, or PORT placement are allowed). 13\. Prior allogeneic bone marrow transplantation or solid organ transplantation. 14\. History of substance abuse or psychiatric disorders that cannot be controlled or withdrawn. 15\. History of immunodeficiency, including positive HIV test, other acquired or congenital immunodeficiency diseases, organ transplantation, or allogeneic bone marrow transplantation. 16\. Currently participating in another interventional clinical study, unless it is an observational (non-interventional) study or the follow-up phase of an interventional study. 17\. Pregnant or lactating women. 18. Any other condition that, in the investigator's judgment, would compromise the subject's safety, hinder compliance, or necessitate premature study termination (e.g., severe concomitant illness, alcoholism, drug abuse, or social/familial circumstances).