Brigatinib, a next-generation ALK tyrosine kinase inhibitor (TKI), had clinically meaningful efficacy in Japanese patients with ALK-positive non-small cell lung cancer (NSCLC) refractory to alectinib, according to the results of a phase 2 study.

“The results of this study show that brigatinib is a promising treatment in patients with ALK+ NSCLC who are refractory to alectinib with or without prior crizotinib, although additional studies in larger patient populations are needed,” the researchers wrote.

According to the study, the majority of patients with ALK-positive NSCLC will eventually progress on first-line TKIs crizotinib or alectinib. This study was designed to test brigatinib in patients who had progressed on these prior therapies.

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In the open-label study, 9 patients were treated as part of a safety lead-in and given 180 mg brigatinib once daily for 7 days followed by 90 mg once daily. Once the regimen was confirmed to be tolerable, the expansion phase was started and included 47 patients.

Seventeen patients who had received treatment with other combinations of up to 2 prior ALK TKIs were included in an exploratory analysis but not in the primary efficacy analysis. The primary endpoint was independent review committee (IRC)–confirmed objective response rate.

With a median follow-up of more than 1 year, 14 of 47 alectinib-refractory patients remained on brigatinib. Of these patients, the IRC-assessed confirmed ORR was 34%, with a median duration of response of 11.8 months. Disease-control rate was 79%. The median time to response was 1.9 months.

The median IRC-assessed progression-free survival was 7.3 months.

“Brigatinib showed activity against alectinib-resistant brain metastases, with an intracranial ORR of 25% in alectinib-refractory patients with brain metastases at baseline,” the researchers wrote.

Brigatinib also showed antitumor activity in patients with G1202R, I1171N, V1180L, and L1196M secondary ALK mutations.


Nishio M, Yoshida T, Kumagai T, et al. Brigatinib in Japanese patients with ALK-positive non-small cell lung cancer previously treated with alectinib and other tyrosine kinase inhibitors: outcomes of the phase-2 J-ALTA trial. J Thorac Oncol. Published online November 25, 2020. doi:10.1016/j.jtho.2020.11.004