389 A phase 1, dose-escalation, first-in-human study of ARQ 087, an oral pan-FGFR inhibitor, in adult subjects with advanced solid tumors

EGFR, genomic analysis revealed an enrichment of KEAP1 mutations in TTF1-negative LUAD. Consistent with this finding, higher expression of Nrf2 (inhibited by KEAP1) was also observed in TTF1-negative tumors, indicating agents that target Nrf2 in these patients. Like patient tumors, LUAD cell lines also demonstrate a bimodal expression of TTF1 with TTF1-negative and positive groups. Consistent with their overexpression of DNA repair proteins, TTF1-negative cell lines had greater sensitivity to drugs with activity against DNA repair proteins. Conclusions: RPPA is a robust method to assay TTF1 expression. Molecular analysis indicates that TTF1-negative patient tumors overexpress multiple DNA repair proteins and Nrf2 and may respond preferentially to drugs against these targets.