eligibility_summary
Inclusion: ≥18 with unresectable/metastatic MSS CRC with KRAS G12C, ≥1 prior line with progression/intolerance, measurable disease, ECOG 0–1, adequate labs, able to take oral meds, recovered to ≤G1, agree to mandatory biopsies and contraception. Exclusion: prior PD‑1/CTLA‑4 or KRAS G12C inhibitors, active autoimmune/immunosuppression, active brain/leptomeningeal mets, prohibitive DDIs (CYP3A/P‑gp/BCRP/QTc), major surgery <4 wks, malabsorption, pregnancy/breastfeeding, uncontrolled HIV/HBV/HCV, uncontrolled illness.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Multicenter Phase 1b/2 single-arm trial in metastatic MSS colorectal cancer with KRAS G12C. Interventions: Adagrasib—oral small‑molecule covalent KRAS G12C inhibitor that locks KRAS in the inactive GDP-bound state, shutting down RAS–RAF–MEK–ERK (MAPK) signaling. Cetuximab—IV chimeric IgG1 anti‑EGFR monoclonal antibody that blocks EGFR ligand binding/signaling and triggers ADCC. Cemiplimab—IV human IgG4 anti‑PD‑1 monoclonal antibody that releases T‑cell exhaustion to restore antitumor immunity. Targets/pathways: KRAS G12C–mutant tumor cells and MAPK pathway, EGFR-driven upstream signaling/feedback that contributes to resistance to KRAS G12C inhibition, PD‑1/PD‑L1 immune checkpoint to enhance T‑cell responses. Immune cells engaged: CD8+ T cells (PD‑1 blockade) and NK cells/macrophages (cetuximab-mediated ADCC).