eligibility_summary
Eligibility: Metastatic (Stage IV) colorectal adenocarcinoma with BRAF V600E, measurable disease (RECIST 1.1), progressed after 1–2 prior metastatic regimens, adequate marrow, liver, and renal function. Exclude: progression during screening, leptomeningeal or symptomatic brain mets, pancreatitis, inability to take oral meds, major CV disease, pneumonitis, active infections (incl. HIV, HBV, HCV), recent other cancers, prior allogeneic transplant, pregnant/breastfeeding.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Trial: Phase 1/2 open-label study (terminated) testing ZN‑c3 + encorafenib + cetuximab in adults with BRAF V600E–mutant metastatic colorectal cancer. Drugs and mechanisms (type): • ZN‑c3: oral small‑molecule WEE1 kinase inhibitor (cell‑cycle checkpoint inhibitor). Blocks WEE1, abrogating the G2/M checkpoint, increasing CDK1/2 activity, replication stress, and DNA damage to drive mitotic death. • Encorafenib (BRAFTOVI): oral small‑molecule BRAF inhibitor that selectively inhibits mutant BRAF V600E, suppressing MAPK/ERK signaling. • Cetuximab (ERBITUX): chimeric IgG1 monoclonal antibody against EGFR, blocks ligand‑mediated EGFR activation and MAPK signaling and can induce ADCC. Targeted cells/pathways: BRAF V600E colorectal tumor cells, EGFR on tumor cells, EGFR–RAS–RAF–MEK–ERK pathway, cell‑cycle G2/M checkpoint and DNA damage response.