eligibility_summary
Adults (≥18) with metastatic/locally advanced HNSCC (oropharynx, oral cavity, hypopharynx, larynx) after progression on anti‑PD‑1 and platinum, p16 status for OPSCC, measurable disease, available tumor sample/FFPE, ECOG 0–1, life expectancy ≥12 wks, adequate organ function. Exclude: active/untreated CNS or leptomeningeal disease, recent therapy/surgery/radiation, >Grade 1 toxicities, drug hypersensitivity, serious cardiac/illness/infections, dyspnea/oxygen, pregnant/breastfeeding, nasopharynx primary.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
NCT06496178: Phase 3, open-label RCT in previously treated metastatic/recurrent HNSCC (post anti–PD-1 and platinum). Interventions: Petosemtamab (MCLA-158), a bispecific IgG1 monoclonal antibody immunotherapy targeting EGFR and LGR5, vs investigator’s choice: cetuximab (anti-EGFR mAb), methotrexate (antifolate antimetabolite), or docetaxel (taxane). Mechanisms/targets: Petosemtamab binds EGFR and LGR5 on tumor cells to inhibit EGFR signaling (MAPK/PI3K-AKT), promote receptor internalization, and trigger Fc-mediated ADCC to eliminate EGFR+/LGR5+ HNSCC, including cancer stem–like cells. Cetuximab blocks EGFR ligand binding and mediates ADCC. Methotrexate inhibits DHFR, reducing thymidine/purine synthesis. Docetaxel stabilizes microtubules, causing mitotic arrest.