eligibility_summary
Eligibility: Informed consent, adults >=18 with ECOG 0-1, >3-month life expectancy, confirmed advanced KRAS G12C-mutant NSCLC, measurable disease, adequate organ function, prior toxicities resolved (<=G1, neuro/alopecia <=G2), contraception required. Exclude: significant CV disease, active CNS mets/meningitis, significant GI disease, active infection, uncontrolled effusions/systemic disease, prior KRAS G12C inhibitor, major surgery <4 wks, drug allergy, pregnancy/lactation.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Trial: Phase Ib/II, single-arm, open-label in previously untreated advanced KRAS G12C–mutant NSCLC. Interventions and mechanisms: - GFH925: oral, small-molecule, covalent KRAS G12C inhibitor, selectively binds the inactive GDP-bound KRAS bearing the Cys12 mutation to shut down oncogenic signaling. - Cetuximab: IV chimeric IgG1 monoclonal antibody against EGFR, blocks ligand binding and receptor dimerization, downregulates EGFR signaling, and can mediate ADCC. Targets/cellular pathways: - Tumor cells harboring KRAS G12C. - Suppression of RAS–RAF–MEK–ERK (MAPK) signaling driven by mutant KRAS. - Inhibition of upstream EGFR signaling to prevent adaptive feedback/reactivation of MAPK and PI3K–AKT pathways. - Potential immune effector engagement (NK-cell–mediated ADCC) against EGFR-expressing tumor cells.