Brigatinib (BRG) in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC): Long-term efficacy and safety results from a phase 1/2 trial

Abstract

Background: The next-generation ALK inhibitor BRG has shown activity in ALK+ NSCLC patients (pts) in clinical trials. Methods: Pts with advanced malignancies (N=137; including 79 pts with ALK+ NSCLC) received oral BRG (30-300 mg/d) in a phase 1/2, open-label, multicenter trial (NCT01449461). We report activity by RECIST v1.1 in ALK+ NSCLC pts and safety in all pts, with long-term follow-up (>31 months since last pt was enrolled). Results: Among 79 ALK+NSCLC pts, median age was 54 years; 90%(71/79) had received prior crizotinib (CRZ). As of 21 Feb 2017, 32% of ALK+NSCLC pts (25/79) and 25% (7/ 28) of those receiving 180mg qd with a 7-day lead-in at 90mg (a regimen evaluated in the phase 2 portion of the trial) continued to receive BRG. Median treatment duration was 20.0 months (1 day to 56.1 months). Confirmed objective response rate (ORR) was 63% (45/71) in pts with prior CRZ and 100% (8/8) in CRZ-naive pts. Additional efficacy data are shown in the table. At 180mg qd (with lead-in), confirmed ORR was 76% (95%CI, 55%-91%) and median progression-free survival (PFS) was 16.3months (95% CI, 9.2- 28.1) in pts with prior CRZ. Treatment-emergent adverse events (AEs) in ≥30%of all 137 pts, mostly grade 1/2, were nausea (55%), fatigue (45%), diarrhea (42%), headache (36%), and cough (34%). Grade ≥3 treatment-emergent AEs in ≥5% of pts were increased lipase (12%), pneumonia (7%), dyspnea (6%), and hypertension (6%). Eleven percent of pts (15/137) discontinued BRG due to an AE. Conclusions: BRG shows major antitumor activity in ALK+ NSCLC pts with an acceptable safety profile in this long-term follow-up. PFS of>16 months in pts receiving 180 mg qd with a 7-day lead-in at 90 mg is among the longest reported in CRZ-resistant ALK+NSCLC. This dosing regimen is being investigated in a randomized phase 3 trial of BRG vs CRZ in ALK inhibitor-naive pts with advanced ALK+NSCLC (ALTA-1L; currently recruiting pts). (Table Presented).