Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1).

摘要: Entrectinib, a potent oral inhibitor of the tyrosine kinases TRKA/B/C, ROS1, and ALK, was evaluated in two phase I studies patients with advanced or metastatic solid tumors, including active central nervous system (CNS) disease. Here, we summarize overall safety report antitumor activity entrectinib cohort tumors harboring NTRK1/2/3, ALK gene fusions, naive to prior TKI treatment targeting specific gene, who were treated at doses that achieved therapeutic exposures consistent recommended II dose. Entrectinib well tolerated, predominantly Grades 1/2 adverse events reversible dose modification. Responses observed non-small cell lung cancer, colorectal mammary analogue secretory carcinoma, melanoma, renal as early 4 weeks after starting lasting long >2 years. Notably, complete CNS response patient SQSTM1-NTRK1-rearranged cancer.Significance: Gene fusions (encoding respectively) lead constitutive activation oncogenic pathways. shown be tolerated against those primary secondary Cancer Discov; 7(4); 400-9. ©2017 AACR.This article is highlighted In This Issue feature, p. 339.