eligibility_summary
Adults ≥18 with metastatic or unresectable recurrent HNSCC (oropharynx/oral cavity/hypopharynx/larynx), PD‑L1 CPS≥1, 1L pembrolizumab‑eligible, no prior systemic therapy for R/M, measurable disease, ECOG 0–1, life expectancy ≥12 wks, adequate organs, LVEF≥50%, tissue available, controlled HIV (CD4≥300, undetectable, on ART) allowed. Exclude: active/symptomatic CNS mets/leptomeningeal, recent therapy/surgery/radiation, immunosuppression/steroids, unresolved ≥G2 AEs, hypersensitivity, major cardiac/respiratory/infectious illness, pregnancy, recent other malignancy, autoimmune needing treatment, prior allogeneic transplant, nasopharyngeal/sinonasal primary.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 3, first-line PD-L1+ recurrent/metastatic HNSCC comparing petosemtamab + pembrolizumab vs pembrolizumab. Petosemtamab (MCLA-158) is a bispecific IgG1 monoclonal antibody targeting EGFR and LGR5, it inhibits EGFR-driven signaling (MAPK/PI3K pathways) and leverages Fc-mediated cytotoxicity/phagocytosis to eliminate LGR5+ tumor stem-like cells, aiming to spare normal tissue. Pembrolizumab is a humanized IgG4 anti-PD-1 checkpoint inhibitor that blocks PD-1/PD-L1, reinvigorating cytotoxic T-cell activity. Targets: EGFR-overexpressing HNSCC cells, LGR5+ cancer stem cells, and the PD-1 pathway on T cells.