PF-06463922, an ALK/ROS1 Inhibitor, Overcomes Resistance to First and Second Generation ALK Inhibitors in Preclinical Models.

摘要: We report the preclinical evaluation of PF-06463922, a potent and brain-penetrant ALK/ROS1 inhibitor. Compared with other clinically available ALK inhibitors, PF-06463922 displayed superior potency against all known acquired mutations, including highly resistant G1202R mutant. Furthermore, treatment led to regression EML4-ALK-driven brain metastases, leading prolonged mouse survival, in manner. Finally, demonstrated high selectivity safety margins variety studies. These results suggest that will be effective for patients ALK-driven lung cancers, those who relapsed on inhibitors because secondary kinase domain mutations and/or metastases.