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 clinically acquired ALK mutations, including the highly resistant G1202R mutant. Furthermore,
PF-06463922 treatment led to regression of EML4-ALK-driven brain metastases, leading to prolonged mouse
survival, in a superior manner. Finally, PF-06463922 demonstrated high selectivity and safety margins in a
variety of preclinical studies. These results suggest that PF-06463922 will be highly effective for the treatment
of patients with ALK-driven lung cancers, including those who relapsed on clinically available ALK inhibitors
because of secondary ALK kinase domain mutations and/or brain metastases. READ ARTICLE
Cell Cancer DOI:10.1016/j.ccell.2015.05.010
Authors: Helen Y. Zou, Luc Friboulet, David P. Kodack, Lars D. Engstrom, Qiuhua Li, Melissa West, Ruth W. Tang, Hui Wang, Konstantinos Tsaparikos, Jinwei Wang, Sergei Timofeevski, Ryohei Katayama, Dac M. Dinh, Hieu Lam, Justine L. Lam, Shinji Yamazaki, Wenyue Hu, Bhushankumar Patel, Divya Bezwada, Rosa L. Frias, Eugene Lifshits, Sidra Mahmood, Justin F. Gainor, Timothy Affolter, Patrick B. Lappin, Hovhannes Gukasyan, Nathan Lee, Shibing Deng, Rakesh K. Jain, Ted W. Johnson, Alice T. Shaw, Valeria R. Fantin and Tod Smeal
