Targeting the EGFR and Immune Pathways in Squamous Cell Carcinoma of the Head and Neck (SCCHN): Forging a New Alliance

DOI: 10.1158/1535-7163.MCT-19-0214 Published November 2019

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Figure 1.
Resistant mechanisms of EGFR-targeted therapy. The following molecular activities will result in bypassing EGFR blockade: (A) Activation mutations or amplification of EGFR downstream signaling effectors; (B) Overexpression of MET proto-oncogene and expression of EGFR variant III; (C) Heterodimerization between EGFR family members; and (D) Activation of TGFβ–IL6 axis.

Table 1.

Ongoing and published clinical trials combining EGFR monoclonal antibodies with immunotherapeutic agents in SCCHN

Design	Title	Trial number	Status
Phase II	A Phase I/II Study of Concurrent Cetuximab and Nivolumab in Patients with Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma	NCT03370276	Recurrent or metastatic
Phase III	Randomized Trial of Avelumab-cetuximab-radiotherapy Versus SOCs in LA SCCHN (REACH)	NCT02999087	Locoregional
Phase III (terminated)	Nivolumab or Nivolumab Plus Cisplatin or Cetuximab, in Combination with Radiotherapy in Patients with Cisplatin-ineligible or Eligible Locally Advanced Squamous Cell Head and Neck Cancer	NCT03349710	Locoregional
Phase I	Phase I trial of cetuximab, intensity modulated radiotherapy (IMRT), and the anti-CTLA-4 monoclonal antibody (mAb) ipilimumab in previously untreated, locally advanced head and neck squamous cell carcinoma (PULA HNSCC)	NCT 0193592	Locoregional
Phase II	Motolimod and Standard Combination Chemotherapy with Cetuximab in Treatment of Patients with Squamous Cell Carcinoma of the Head and Neck: The Active8 Randomized Clinical Trial.	NCT01836029	Recurrent and metastatic SCCHN (manuscript published; ref. 88).
Phase II	EACH: Evaluating Avelumab in Combination with Cetuximab in Head and Neck Cancer (EACH)	NCT03494322	Locoregional