Glecirasib Combined With Ivonescimab for First-line Treatment of KRAS G12C-mutated NSCLC

Inclusion Criteria:

* Signed written informed consent.
* Age ≥18 years.
* Newly diagnosed, unresectable, locally advanced (ineligible for curative concurrent - chemoradiotherapy) or metastatic NSCLC per AJCC 9th edition.
* KRAS G12C mutation confirmed by validated testing.
* PD-L1 TPS ≥1%.
* ≥1 measurable lesion per RECIST v1.1.
* No prior systemic therapy for advanced/metastatic NSCLC; prior adjuvant therapy allowed if completed \>6 months before dosing and toxicities recovered to ≤Grade 1.
* ECOG PS 0-2.
* Life expectancy \>3 months
* Adequate organ function (hematologic, hepatic, renal, coagulation per protocol thresholds)
* Negative pregnancy test for women of childbearing potential; adequate contraception for men and women through 3 months post-treatment
* Willing and able to comply with study procedures and follow-up.

Exclusion Criteria:

* History of other malignancies (exceptions: cured basal cell carcinoma, cervical carcinoma in situ)
* Predominant squamous NSCLC, small cell carcinoma, or neuroendocrine carcinoma.
* Other actionable drivers (EGFR, ALK, ROS1, RET, BRAF, NTRK, MET, etc.).
* Known hypersensitivity to study drugs.
* Prior PD-1/PD-L1 inhibitors or KRAS inhibitors.
* Active autoimmune disease or autoimmune disease history requiring systemic therapy.
* Systemic immunosuppressive therapy within 14 days prior to first dose.
* Symptomatic ascites/pleural effusion needing recurrent drainage.
* Significant cardiovascular disease (NYHA ≥2, MI within 1 year, uncontrolled arrhythmias).
* Active infection, unexplained fever \>38.5°C.
* Interstitial lung disease or pneumonitis.
* HIV infection or other immunodeficiency.
* Live vaccines within 4 weeks.
* Substance abuse, alcoholism, or psychiatric disorders impairing compliance.
* Unable to swallow oral medication.
* Any condition that may interfere with study participation or interpretation as judged by investigator.