Abstract 772: Anti-tumor efficacy of the selective pan-FGFR Inhibitor BAY 1163877 in preclinical squamous cell carcinoma models of different origin

Squamous cell carcinoma (SCC) is a common subtype of lung cancer and is strongly associated with smoking. In contrast to adenocarcinomas of the lung, SCCs do not significantly harbor epidermal growth factor (EGFR) mutations or ALK, ROS1 or RET translocations, which are therapeutically tractable. SCC of the lung and SCC of the head and neck region and esophagus not only share risk factors, morphologic features and mechanisms of tumorigenesis but also frequent fibroblast growth factor receptor 1 (FGFR1) gene alterations. In addition, we found that FGFR2 and FGFR3 expression were also altered in patient derived models of SCC of various origins. FGFRs may thus represent viable therapeutic targets for the treatment of SCC.BAY 1163877, an orally available and potent inhibitor of FGFR1, FGFR2 and FGFR3, inhibited SCC cell proliferation as well as downstream FGFR signaling in vitro. When applied in vivo, BAY 1163877 was able to reduce growth of a FGFR1-overexpressing lung SCC xenograft model, a FGFR1-overexpressing esophageal SCC xenograft model, and a FGFR3-overexpressing head and neck SCC xenograft model, achieving reductions in tumor growth by 67 to 92% as compared to the vehicle control. BAY 1163877 was very well tolerated in all models performed.These data suggest that selective inhibition of FGFR1 to 3 with BAY 1163877 might have therapeutic potential for the treatment of SCC malignancies. A phase I clinical trial (NCT01976741) to determine the safety, tolerability and recommen...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Experimental and Molecular Therapeutics Source Type: research