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Alectinib Granted Priority Review for Use in Certain NSCLC Cases

The FDA is set to make a decision on the NDA by March 2016

The FDA has accepted the new drug application (NDA) and granted priority review for alectinib (Genentech), an oral investigational anaplastic lymphoma kinase (ALK) inhibitor, for the treatment of patients with ALK-positive, locally advanced or metastatic non–small-cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib.

The FDA designated alectinib a breakthrough therapy in June 2013 for people with ALK-positive NSCLC whose disease has progressed on crizotinib.

A priority review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention, or diagnosis of a disease. Breakthrough therapy designation is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases and to help ensure people have access to them through FDA approval as soon as possible.

The NDA for alectinib includes data from two phase II studies (NP28761 and NP28673). The FDA will make a decision by March 4, 2016.

Results from NP28761 and NP28673 were presented at the 2015 Annual Meeting of the American Society of Clinical Oncology.

NP28761 is a North American, single-arm, open-label, multicenter trial evaluating the safety and efficacy of alectinib in 87 people with ALK-positive NSCLC whose disease progressed on crizotinib. A response assessment by an independent review committee (IRC) showed that alectinib shrank tumors (the objective response rate, ORR) in 47.8% (95% confidence interval [CI], 35.6–60.2%) of people treated with alectinib, as measured by Response Evaluation Criteria in Solid Tumors (RECIST v1.1).

Among people whose disease had already spread to the brain or other parts of the central nervous system (CNS) at study entry, the IRC found a CNS ORR of 68.8% (95% CI, 41.3–89.0%). People whose tumors shrank in response to alectinib continued to respond for a median of 7.5 months (duration of response [DOR], immature data). The immature median progression-free survival (PFS) was 6.3 months (95% CI, 5.5–not estimable) based on 40% of events.

The most common grade 3 or higher adverse events were increased blood levels of creatine phosphokinase (8%), increased liver enzymes (alanine aminotransferase, 6%, and aspartate aminotransferase, 5%) and dyspnea (3%).

NP28673 is a global, single-arm, open-label, multicenter trial evaluating the safety and efficacy of alectinib in 138 people with ALK-positive NSCLC whose disease progressed on crizotinib. An IRC analysis showed an ORR for alectinib of 50.0% (95% CI, 40.8–59.1%) in this group, as measured by RECIST. The IRC also found a CNS ORR of 57.1% (95% CI, 39.4–73.7%) in people whose disease had already spread to the brain or other parts of the CNS at study entry. Among people who achieved a response, the DOR was a median 11.2 months (immature data based on 33% of events [95% CI, 9.6 months–not estimable]). The median PFS for people who received alectinib was 8.9 months (95% CI, 5.6–11.3) based on 58%of events.

The most common grade 3 or higher adverse event was dyspnea (4%).

Source: Genentech; September 8, 2015.

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