eligibility_summary
Key eligibility: Adults 18–<80, ECOG 0–1, untreated stage III–IVB LA‑SCCHN of oral cavity, hypopharynx or larynx, OPC if HPV–, or HPV+ smokers >20 PY with T3N1–3 or T4. Able to swallow or use feeding tube. Ineligible for high‑dose cisplatin. Adequate labs/organ function, contraception, consent. Exclude: metastasis, non‑eligible sites, HIV/HBV/HCV, active infection, malabsorption/major wt loss, bleeding, major CV/HTN/resp disease, recent cancers, cirrhosis, prior HN RT/systemic Tx, QT‑risk meds/trials, allergy, pregnancy.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Interventions: Xevinapant (oral small‑molecule SMAC mimetic, antagonist of inhibitor of apoptosis proteins XIAP, cIAP1/2, ML‑IAP) plus intensity‑modulated radiotherapy (IMRT) and cetuximab (chimeric IgG1 anti‑EGFR monoclonal antibody) versus IMRT+cetuximab+placebo in locally advanced SCCHN patients unfit for high‑dose cisplatin. Mechanisms: Xevinapant blocks IAPs to restore caspase‑mediated apoptosis and enhance TNF‑α–dependent cell death, yielding radio‑sensitization and immunomodulatory effects. Cetuximab inhibits EGFR signaling (RAS/RAF/MEK/ERK, PI3K/AKT), impairs DNA repair/cell cycle, and triggers ADCC via NK cells, also increasing radio‑sensitivity. IMRT causes DNA double‑strand breaks and tumor kill. Targets: HNSCC tumor cells, pathways include EGFR signaling, IAP‑regulated apoptosis/NF‑κB, TNF death signaling, and DNA damage response, engages immune effector cells (NK cells). Trial status: terminated for toxicity.