Ceritinib for ALK-Rearranged Non–Small-Cell Lung Cancer

Crizotinib-resistance in ALK-translocation–positive non–small-cell Lung Cancer (NSCLC) is a major problem that often occurs within 1 year of treatment. One-third of patients are known to develop resistance via acquired mutations in the ALK tyrosine kinase domain or ALK gene amplification. Ceritinib is a second-generation oral tyrosine kinase inhibitor of ALK. Ceritinib does not target the MET prototype oncogene but inhibits the insulin-like growth factor 1 receptor and, in preclinical models, had 20 times more potency against ALK than crizotinib.

To further assess the safety and activity of ceritinib, investigators conducted an industry-sponsored dose-escalation and expansion phase I study involving 130 patients with ALK-rearranged solid tum…