Multicenter phase 2 trial of ficlatuzumab with or without cetuximab for pan-refractory recurrent or metastatic head and neck cancer

Primary or acquired resistance to the anti-EGFR mAb cetuximab minimizes its utility in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Aberrant HGF/cMet pathway activation is an established resistance mechanism. A multicenter randomized phase 2 trial evaluated the anti-HGF mAb ficlatuzumab with or without cetuximab for triple-refractory R/M HNSCC. The combination arm met significance criteria for PFS, with an median PFS of 3.7 months. The ORR in the combination arm was 19%, including complete response in 6%. Exploratory analysis showed significantly higher activity in HPV-negative disease when compared with HPV-positive disease. The authors conclude that the combination of ficlatuzumab and cetuximab for triple-refractory R/M HNSCC warrants phase 3 testing while HPV-negative disease merits consideration as a selection criterion.