eligibility_summary
Incl: 18–75, R/M HNSCC post PD‑1/PD‑L1 + platinum (≤2 lines), no curative option, measurable disease, ECOG 0–1, tissue/blood biomarkers, neg pregnancy test/contraception. Excl: Nasal/paranasal/nasopharynx/salivary primaries, prior HER3/EGFR therapy, CNS mets, active HIV/HBV/HCV/TB/syphilis, unresolved toxicities, recent therapy/surgery/live vaccine, serious lung/CV disease, QTc↑/LVEF<50%, recent thrombosis, pregnancy/lactation, chronic high‑dose steroids, uncontrolled effusions.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Interventions: SIBP‑03 (HER3/ERBB3 monoclonal antibody, IV every 3 weeks, dose-finding to RP2D) combined with cetuximab (EGFR/HER1 monoclonal antibody, IV weekly) versus placebo + cetuximab. Mechanisms: SIBP‑03 blocks HER3, inhibiting heregulin (NRG1)-driven activation and HER2/EGFR–HER3 heterodimer signaling, suppressing downstream PI3K/AKT and MAPK pathways, as an IgG mAb it may also mediate ADCC. Cetuximab binds EGFR, preventing ligand binding and dimerization, promoting receptor downregulation and ADCC, dampening RAS/RAF/MEK/ERK and PI3K/AKT signaling. Targets: Tumor cells in recurrent/metastatic HNSCC expressing HER3 and EGFR, ERBB family signaling axis, potential engagement of immune effector cells (e.g., NK cells via Fcγ receptors). Design: Phase IIa dose selection, followed by randomized double-blind Phase IIb vs placebo, all with cetuximab.