With this perspective, combinatorial treatment strategies emerged to simultaneously target both the primary tumor’s molecular signature (e.g. EGFR) as well as the signaling mechanism likely to develop (e.g. HER3) upon resistance to first line therapy16. MEHD7945A or duligotuzumab, is a single agent fully human IgG1 monoclonal antibody (mAb) that targets both EGFR (KD ~ 1.9 nM) and HER3 (KD ~ 0.4 nM)17. It was developed to improve treatment response of solid tumors confounded with HER3-mediated resistance to EGFR-targeted treatment17. It is also efficacious in tumors refractory to both radiation and prolonged EGFR-specific treatment18,19. Importantly, it is safely tolerated by patients with locally advanced or metastatic epithelial cancers with no dose-limiting toxicities20. Partial response rates have been achieved in patients with cetuximab-refractory and prior chemo radiation squamous cell carcinoma of the head and neck (SCCHN)20.