Shirish M Gadgeel 1 , Leena Gandhi 2 , Gregory J Riely 3 , Alberto A Chiappori 4 , Howard L West 5 , Michele C Azada 6 , Peter N Morcos 7 , Ruey-Min Lee 7 , Linta Garcia 8 , Li Yu 7 , Frederic Boisserie 7 , Laura Di Laurenzio 7 , Sophie Golding 7 , Jotaro Sato 9 , Shumpei Yokoyama 9 , Tomohiro Tanaka 9 , Sai-Hong Ignatius Ou 10
Patients with non-small-cell lung cancer (NSCLC) and ALK rearrangements generally have a progression-free survival of 8-11 months while on treatment with the ALK inhibitor crizotinib. However, resistance inevitably develops, with the brain a common site of progression. More potent ALK inhibitors with consistently demonstrable CNS activity and good tolerability are needed urgently. Alectinib is a novel, highly selective, and potent ALK inhibitor that has shown clinical activity in patients with crizotinib-naive ALK-rearranged NSCLC. We did a phase 1/2 study of alectinib to establish the recommended phase 2 dose of the drug and examine its activity in patients resistant or intolerant to crizotinib.