Brigatinib (BRG) in patients (pts) with ALK+ non-small cell lung cancer (NSCLC): updates from a phase 1/2 trial

Background: The investigational next‐generation ALK inhibitor BRG has shown activity in ALK+ NSCLC pts in a phase 1/2 trial; here, we provide updated data with longer follow‐up. Methods: In this ongoing phase 1/2, single‐arm, open‐label, multicenter trial (NCT01449461), pts with advanced malignancies (including ALK+ NSCLC) received oral BRG (30‐300 mg/d). Activity by RECIST v1.1 in ALK+ NSCLC pts and safety in all pts are shown. Results: 58% (79/137) pts had ALK+ NSCLC, with median age 54 y; of these, 90% (71/79) had received crizotinib (CRZ). As of May 31, 2016, 41% (32/79) ALK+ NSCLC pts continued to receive BRG; median treatment duration was 20.0 mo (1 d‐47.4 mo). The table shows efficacy in CRZ‐treated pts; median overall survival was 47.6 mo (95% CI 21.4‐47.6 mo). All 8 CRZ‐naive pts had confirmed objective responses; median duration of response and progression‐free survival (PFS) were not reached. In a post hoc analysis, 53% (95% CI 27%‐79%; 8/15) ALK+ NSCLC pts with measurable baseline brain metastases had confirmed intracranial objective responses (last scan date: October 8, 2015). Median intracranial PFS in 46 evaluable ALK+ NSCLC pts with baseline brain metastases was 14.6 mo (95% CI 12.7‐36.8 mo). Treatment‐emergent adverse events (AEs) in ≥30% of all pts, mainly grade 1/2, were nausea 53%, fatigue 45%, diarrhea 42%, headache 35%, and cough 33%; serious treatment‐emergent AEs in ≥5% of pts were pneumonia 7%, dyspnea 6%, and hypoxia 5%. 10% of pts (14/137) discontinued BRG due to an AE. Conclusions: BRG yielded substantial whole‐body and intracranial activity in ALK+ NSCLC pts in this trial, with acceptable safety. These data informed design of the pivotal randomized phase 2 trial of BRG (90 mg qd or 180 mg qd [with lead‐in]) in CRZ‐refractory ALK+ NSCLC (ALTA). (Table Presented).