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.
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.
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.