Abstract 3774: Unraveling mechanisms of resistance to tepotinib and future treatment options

Background Advanced non-small cell lung cancer (NSCLC) patients with MET exon 14 skipping mutations (METex14) or MET amplification (METamp) derive benefit from MET tyrosine kinase inhibitors (TKIs). Tepotinib is an investigational selective MET TKI. Co-occurring MAPK pathway alterations in MET dependent tumors are frequent and may induce primary or acquired resistance to MET TKIs. Methods METamp (EBC1, NCI-H1993 and MNK-45) and METex14 (Hs746T) cells were obtained from commercial vendors. Tepotinib-resistant (TR) cells (EBC1-TR1, -TR2 and Hs746T-TR) were generated upon continuous exposure of EBC1 and Hs746T cells to tepotinib. The phosphorylation of 49 receptor tyrosine kinases (RTK) and 43 non-RTKs was assessed using Human Phospho‐RTK kinase Array Kits (RD 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3774.