This phase 2 trial evaluated efficacy and safety of brigatinib in patients with advanced anaplastic lymphoma kinase (ALK)-positive NSCLC refractory to alectinib and/or other ALK tyrosine kinase inhibitors (TKIs).
This single-arm, multicenter, open-label study in Japanese patients consisted of a safety lead-in followed by an expansion stage in ALK TKI-refractory or -naive patients. Patients received brigatinib 180 mg once daily with 7-day lead-in at 90 mg once daily. Primary end point was independent review committee (IRC)-assessed confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1.
We report results of the lead-in and expansion in ALK TKI-refractory patients. Of 72 patients enrolled, 47 had alectinib as most recent ALK TKI (with or without prior crizotinib). At analysis cutoff, 14 of the 47 remained on brigatinib (median follow-up: 12.4 months). In the alectinib-refractory population, IRC-assessed confirmed ORR was 34% (95% confidence interval [CI], 21%-49%) with median duration of response of 11.8 months (95% CI, 5.5-16.4). Disease control rate was 79% (95% CI, 64%-89%). Median IRC-assessed progression-free survival was 7.3 months (95% CI, 3.7-9.3). Two of eight patients with measurable brain lesions at baseline had confirmed intracranial partial response. Brigatinib showed antitumor activity in patients with G1202R, I1171N, V1180L, and L1196M secondary mutations. The safety profile in Japanese patients was consistent with previous reports in broader populations.
Brigatinib showed clinically meaningful efficacy in Japanese patients with ALK+ NSCLC refractory to alectinib (with or without prior crizotinib).

Copyright © 2020. Published by Elsevier Inc.