Brigatinib in Japanese patients with ALK‐positive non‐small‐cell lung cancer: Final results of the phase 2 J‐ALTA trial

The phase 2, single‐arm, multicenter, open‐label J‐ALTA study evaluated the efficacy and safety of brigatinib in Japanese patients with advanced ALK+ non‐small‐cell lung cancer (NSCLC). One expansion cohort of J‐ALTA enrolled patients previously treated with ALK tyrosine kinase inhibitors (TKIs); the main cohort included patients with prior alectinib ± crizotinib. The second expansion cohort enrolled patients with TKI‐naive ALK+ NSCLC. All patients received brigatinib 180 mg once daily (7‐day lead‐in at 90 mg daily). Among 47 patients in the main cohort, 5 (11%) remained on brigatinib at the study end (median follow‐up: 23 months). In this cohort, the independent review committee (IRC)‐assessed objective response rate (ORR) was 34% (95% CI, 21%–49%); median duration of response was 14.8 months (95% CI, 5.5–19.4); median IRC‐assessed progression‐free survival (PFS) was 7.3 months (95% CI, 3.7–12.9). Among 32 patients in the TKI‐naive cohort, 25 (78%) remained on brigatinib (median follow‐up: 22 months); 2‐year IRC‐assessed PFS was 73% (90% CI, 55%–85%); IRC‐assessed ORR was 97% (95% CI, 84%–100%); the median duration of response was not reached (95% CI, 19.4–not reached); 2‐year duration of response was 70%. Grade ≥3 adverse events occurred in 68% and 91% of TKI‐pretreated and TKI‐naive patients, respectively. Exploratory analyses of baseline circulating tumor DNA in ALK TKI‐pretreated NSCLC showed associations between poor PFS and EML4‐ALK fusion variant 3 and TP53. Brigatinib is an important treatment option for Japanese patients with ALK+ NSCLC, including patients previously treated with alectinib.