eligibility_summary
Eligibility: measurable/evaluable disease, ECOG 0–1, ≥12‑wk life expectancy, adequate organs. NSCLC: unresectable/metastatic EGFR ex19del or L858R adenocarcinoma, progressed after 3rd‑gen EGFRi (e.g., osimertinib), no acquired on‑target EGFR changes. CRC: metastatic, post‑EGFRi, KRAS/NRAS WT, BRAF V600E WT. Key excludes: recent therapy/surgery, hepatitis B/C or HIV, liver disease, hypercalcemia, poor absorption/diarrhea or can’t swallow pills, serious infection, recent cancer, active CNS/lepto, ECG/MI/low LVEF, eye disease, major CV, pulmonary fibrosis/pneumonitis.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Drugs/interventions: • GDC-1971 (RO7517834/RLY-1971): oral small-molecule, allosteric inhibitor of SHP2 (PTPN11), a phosphatase that couples receptor tyrosine kinases (RTKs) to RAS activation. • Osimertinib: oral, third‑generation, mutant‑selective, irreversible EGFR tyrosine kinase inhibitor. • Cetuximab: IV chimeric IgG1 monoclonal antibody against EGFR, blocks ligand binding/receptor activation and can elicit ADCC. Target cells/pathways: • SHP2–SOS1–RAS–RAF–MEK–ERK (MAPK) signaling downstream of RTKs, combinations aim to prevent/bypass reactivation of RAS–MAPK that drives resistance to EGFR inhibitors. • EGFR-driven tumor cells: EGFR‑mutant NSCLC (Ex19del/L858R) and RAS/NRAS/BRAF WT mCRC after prior anti‑EGFR therapy. Overall, the trial tests dual EGFR blockade (TKI or antibody) plus SHP2 inhibition to suppress RTK/EGFR-dependent MAPK signaling in cancer cells.