This study evaluates the safety, tolerability, maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and recommended phase II dose (RP2D) of Glecirasib in combination with Ivonescimab in patients with previously untreated, KRAS G12C-mutated, locally advanced or metastatic non-small cell lung cancer (NSCLC) with PD-L1 TPS ≥1%. The study includes a Phase I 3+3 dose-escalation stage followed by a Phase II Simon two-stage design to assess preliminary antitumor efficacy.

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.