Due to strong preclinical rationale, the hypothesis that dual EGFR-ErbB3 blockade could improve oncologic outcomes relative to EGFR inhibition alone was previously investigated in a phase II randomized trial of duligotuzumab, a dual-action humanized IgG1 antibody that blocks ligand binding to EGFR and ErbB3, vs. cetuximab in patients with platinum-resistant, cetuximab-naïve, HPV-positive or -negative HNSCC [26]. Here, EGFR is linked to head and neck squamous cell carcinoma.