• In the Phase I/II trial (n = 47) in advanced ALK-rearranged NSCLC resistant or intolerant to crizotinib, alectinib was well tolerated with promising activity, including in patients with brain metastases.
• A dose of 600 mg BID of alectinib was recommended for the ongoing Phase II portion of the study.

Another promising next-generation ALK inhibitor is alectinib, which, like ceritinib, results in responses regardless of prior exposure to crizotinib. In this Phase I/II study, objective responses were reported in most patients, including in 11 of 21 patients with brain metastases (52%), an important finding because the CNS is a common site of disease progression in patients receiving crizotinib. Samples of cerebrospinal fluid obtained from 5 patients indicated that alectinib penetrates the CNS compartment. At this point, alectinib does not appear to be associated with significant tolerability concerns, and no dose-limiting toxicity was observed.

The pivotal Phase III ALEX study in patients with newly diagnosed, ALK-rearranged advanced NSCLC compares alectinib to crizotinib and in addition to evaluating standard efficacy outcomes such as PFS is also examining CNS disease control.