Gerber DE, Camidge DR, Morgensztern D, et al. - In view of the ongoing unmet clinical need and strong evidence from preclinical studies suggesting the sensitivity of KRAS mutant non-small cell lung cancer (NSCLC) cell lines and xenografts with additional alterations in either TP53 or CDKN2A (INK4A/ARF) loci to focal adhesion kinase (FAK) inhibition, researchers performed conducted a single-arm, open-label, multi-cohort trial of defactinib (a selective oral inhibitor of FAK) in previously treated advanced KRAS mutant NSCLC. Based on the presence or absence of TP53 or CDKN2A alterations, they assigned 55 patients with previously treated advanced KRAS mutant NSCLC to one of four molecularly defined cohorts; treatment with defactinib 400 mg orally BID was provided to patients until disease progression or intolerable toxicity. Defactinib monotherapy showed modest clinical activity in these heavily pretreated patients with KRAS mutant NSCLC. TP53 and CDKN2A status did not influence the efficacy. Usually, defactinib was well tolerated.