ANOTHER ALK INHIBITOR APPROVED BY FDA

The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to Ariad Pharmaceutical’s investigational agent AP26113 for patients with anaplastic lymphoma kinase (ALK)-positive metastatic non–small cell lung cancer (NSCLC) who are resistant to crizotinib (Xalkori) This designation is based on results from an ongoing phase I/II trial showing sustained antitumor activity of AP26113 in patients with ALK-positive NSCLC, including patients with active brain metastases.

Phase I/II Data

Updated clinical data from the phase I/II trial of AP26113 were recently shared at the ESMO 2014 Congress (Abstract 1292P). A total of 137 patients have been enrolled in the trial in the United States and Europe. Objective responses were observed in ALK-positive NSCLC patients, and responses were observed in patients who were either tyrosine kinase inhibitor–naive or resistant to crizotinib. Of the 72 ALK-positive NSCLC patients evaluable for response, 52 (72%) demonstrated an objective response. The median duration of response was 49 weeks, and the median progression-free survival was 56 weeks.

In a subgroup analysis, 10 of 14 (71%) ALK-positive NSCLC patients with active, untreated, or progressing brain metastases had evidence of radiographic improvement in those metastases. Of the seven evaluable tyrosine kinase inhibitor–naive ALK-positive NSCLC patients treated with AP26113, all demonstrated an objective response, including two complete responses.

The most common adverse events, regardless of treatment relationship and including all grades, were nausea (45%), diarrhea (37%), and fatigue (37%). Adverse events, grade 3 or higher, occurring in three or more patients were dyspnea (4%), increased lipase (4%), hypoxia (4%), fatigue (3%), alanine aminotransferase (ALT) increased (2%), and amylase increased (2%). Serious adverse, all causality, occurring in three or more patients were dyspnea (7%), pneumonia (5%), hypoxia (4%), neoplasm progression (4%), pyrexia (2%), and pulmonary embolism (2%).