eligibility_summary
Adults ≥18 with metastatic/locally advanced KRAS G12D NSCLC/CRC/PDAC, measurable disease, adequate organs, and FFPE sample, progressed/intolerant to SoC. Prior therapy: NSCLC ≥1 line, CRC ≥2, PDAC ≥1, Part C: M1 NSCLC/PDAC 1–2, M2 CRC 2–3. Neo/adjuvant relapse ≤6 mo counts as 1L. M2A CRC, M2B CRC/PDAC, M2C CRC. Food-effect cohort: high-fat meal, 10‑h fast. Exclude major comorbidity, ILD, active CNS disease, transplant, cardiac issues, prior KRAS inhibitor, herbal/CYP3A drugs, inadequate washout/recent RT.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Drugs/interventions: AZD0022—an oral small‑molecule, selective KRASG12D inhibitor that blocks mutant KRAS function/signaling, tested as monotherapy and combined with cetuximab. Cetuximab—chimeric IgG1 monoclonal antibody against EGFR that competitively blocks ligand binding and EGFR activation. Cells/pathways targeted: Tumor cells with KRASG12D mutations (advanced NSCLC, PDAC, CRC). AZD0022 targets the KRAS-driven oncogenic pathway, suppressing downstream RAS‑RAF‑MEK‑ERK (MAPK) and PI3K‑AKT signaling. The combination arm also targets upstream EGFR to curb feedback/reactivation of MAPK signaling, particularly relevant in colorectal and pancreatic tumors.