(EAY 131-G MATCH): Phase II Study of Crizotinib in Patients with ROS1 Translocations (Other Than Patients with Non-Small Cell Lung Cancer)
Description: 
Crizotinib has been studied in a variety of in vitro and in vivo model systems to determine potency for inhibition of ALK, c-MET/HGFR, RON, or ROS1 RTK activity, kinase selectivity, antitumor efficacy, PK/PD relationships, and mechanism of action. Crizotinib demonstrated potent concentration-dependent inhibition of the kinase activity of ALK, c-MET/HGFR, RON, and ROS1 in biochemical assays and inhibited phosphorylation and kinase dependent function in cell-based assays. Crizotinib demonstrated potent and selective growth inhibitory activity and induced apoptosis in tumor cells lines exhibiting ALK fusion variants (EML4-ALK) or NPM-ALK), ROS1 fusion variants, or exhibiting amplification of the ALK or c-MET/HGFR gene locus. In vivo, crizotinib demonstrated potent and selective growth inhibitory activity and induced apoptosis in tumor cell lines exhibiting ALK fusion variants (EML4-ALK or NPM-ALK), ROS1 fusion variants, or exhibiting amplification of the ALK or c-MET/HGFR gene locus. In vivo, crizotinib demonstrated antitumor efficacy, including marked cytoreductive antitumor activity, in mice bearing tumor xenografts that expressed ALK fusion variants or activated c-MET/HGFR. The anti-tumor efficacy of crizotinib was dose-dependent and correlated to pharmacodynamic inhibition of phosphorylation of ALK fusion variants (EML4-ALK or NPM-ALK) or c-MET/HGFR in tumors in vivo. The collective rationale for investigation of crizotinib in clinical studies is built on genetic alteration of its molecular targets, its predicted ability to target multiple processes that are common to cancer progression, and preclinical efficacy data. 7
Study Number: 

NCG 275215 G

Phase: 
2
Principal Investigator: 
ClinicalTrials.Gov ID: 
NCT02465060

To inquire about participating in these studies, call 1-877-ASK-RPCI (1-877-275-7724) or e-mail askrpci@roswellpark.org.