Phase III Study of RC148 Plus Chemotherapy Versus Tislelizumab Plus Chemotherapy as First-Line Treatment for Non-Squamous Non-Small Cell Lung Cancer Without Actionable Genomic Alterations

• 1. Voluntarily agrees to participate in the study and provides written informed consent.

  2. Willing and able to comply with study and follow-up procedures. 3. Male or female, aged 18 to 75 years inclusive. 4. Estimated life expectancy≥3 months. 5. ECOG performance status 0 or 1. 6. Histologically or cytologically confirmed locally advanced or metastatic NSCLC, not amenable to curative-intent therapy.

  7. No prior systemic anti-tumor therapy for advanced or metastatic NSCLC 8. Has at least one measurable non-central nervous system lesion per RECIST v1.1.

  9. Must provide PD-L1 expression testing report and actionable genomic alterations testing report before enrollment.

  10. Adequate cardiac, bone marrow, hepatic, renal, and coagulation function. 11. Female study participants must be postmenopausal, surgically sterile, or, if of childbearing potential, must have a negative serum pregnancy test within 7 days prior to randomization, and agree to use at least one medically acceptable contraceptive method (e.g., intrauterine device, oral contraceptives, or condoms) during study treatment and for 12 months after completion of study treatment. Female participants shall not donate ova or breastfeed during this period. Male study participants must agree to use at least one medically acceptable contraceptive method during study treatment and for 12 months after completion of study treatment, and shall not donate sperm during this period.

Exclusion Criteria:

• 1. Histologically confirmed presence of any squamous NSCLC, small cell carcinoma, neuroendocrine carcinoma, or sarcoma components.

  2. Known actionable gene alterations positive or harboring gene mutations with approved first-line treatment options.

  3. Presence of active brain metastases. 4. Screening imaging demonstrates marked tumor necrosis or cavitation, and the investigator determines that enrollment in this study may confer a risk of bleeding.

  5. Have received chest radiotherapy >30 Gy within 6 months prior to randomization; received palliative local therapy for non-target lesions within 2 weeks prior to randomization; received non-specific immunomodulatory therapy within 2 weeks prior to randomization; or received Chinese herbal or proprietary medicines with anti-tumor indications within 1 week prior to randomization.

  6. Have received immunotherapy, including immune checkpoint inhibitors, immune checkpoint agonists, immune cell therapy, or any other therapy targeting anti-tumor immune mechanisms.

  7. Have received other systemic anti-tumor therapy other than chemotherapy and PD-1/PD-L1 antibodies.

  8. Systemic treatment with corticosteroids or other immunosuppressive drugs within 2 weeks prior to randomization.

  9. Have received any live or live-attenuated vaccine within 4 weeks prior to randomization, or plans to receive any live or live-attenuated vaccine during the study.

  10. Participation in another clinical trial within 4 weeks prior to randomization 11. Have undergone major surgery, interventional therapy, or severe trauma within 4 weeks prior to randomization, or plans to undergo major surgery during the study period; has undergone core needle biopsy or other minor surgical procedures within 7 days prior to randomization.

  12. Have a history of severe coagulation disorder, or is receiving anticoagulant medications, including those using prophylactic-dose anticoagulants.

  13. Toxicities of prior anti-tumor therapy have not recovered to Grade 0-1 per CTCAE v6.0, excluding alopecia, pigmentation, expected irreversible endocrine toxicities secondary to prior immunotherapy that are stably controlled with medications, and other conditions judged by the investigator not to interfere with study drug treatment.

  14. For participants with prior PD-1/PD-L1 inhibitor exposure: prior Grade ≥3 irAEs, irAEs resulting in permanent treatment discontinuation, Grade 2 immune-related cardiac irAEs, or any-grade neurologic or ocular irAEs; prior adverse events requiring immunosuppressants other than corticosteroids, or recurrent adverse events during prior immunotherapy requiring re-administration of systemic corticosteroids.

  15. Have severe acute or chronic infection. 16. Occurrence of hemoptysis, active gastrointestinal bleeding, peptic ulcer, epistaxis, or other bleeding events requiring intervention within 4 weeks prior to randomization, or presence of severe esophagogastric varices, vasculitis, aneurysm, or dissection assessed by the investigator as high bleeding risk.

  17. Serious arterial/venous thromboembolic events, cerebrovascular accident, or hypertensive encephalopathy occurring within 6 months prior to randomization.

  18. Have active or clinically significant cardiac disease. 19. Previous and/or current interstitial lung disease, drug-related pneumonitis, radiation pneumonitis, severely impaired pulmonary function, acute exacerbation of chronic obstructive pulmonary disease within 1 month prior to randomization, or clinical signs or high-risk factors suggestive of interstitial lung disease.

  20. Have a history of gastrointestinal perforation and/or fistula, or gastrointestinal obstruction within 6 months prior to randomization.

  21. Presence of systemic diseases assessed by the investigator as not stably controlled.

  22. Presence of active autoimmune disease, or prior autoimmune disease at risk of recurrence.

  23. Have a history of other acquired or congenital immunodeficiency diseases, or a history of organ transplantation.

  24. Have known hypersensitivity or delayed-type hypersensitivity reactions to any components of the study drug or analogous drugs.

  25. Presence of symptomatic third-space effusion or third-space effusion requiring intervention.

  26. Other malignancy within 5 years before initiation of study treatment. 27. Poor compliance and anticipated inability to comply with trial procedures 28. Previous or current presence of any other disease. 29. Non-malignant local or systemic disorders, or tumor-secondary diseases or symptoms associated with high medical risk and/or uncertainty in survival evaluation, e.g., cachexia.