Background: In previous J-ALTA (NCT03410108) analyses, brigatinib demonstrated substantial efficacy and manageable safety in pts with TKI-refractory and TKI-naive ALK+ NSCLC. We report the final J-ALTA results. Methods: J-ALTA was a single arm, multicenter, open-label study that included ALK TKI-naive and -refractory NSCLC expansion parts. The main cohort within the refractory part was a group with alectinib-refractory NSCLC. Primary endpoints: IRC-assessed confirmed ORR in the alectinib-refractory cohort; IRC-assessed 12-month PFS in the TKI-naive cohort. Secondary endpoints included confirmed ORR (IRC-assessed in the total refractory cohort; investigator-assessed in all cohorts); DoR, PFS, DCR, and iPFS by IRC; and safety. Final analyses were performed following last pt last contact. Results: A total of 104 pts were enrolled; 72 had TKI-refractory (56% female; median age, 53.0 y) and 32 had TKI-naive (53% female; median age, 60.5 y) NSCLC. As of 28 July, 2021 (last pt last contact), median follow-up was 24.2 mo in the refractory cohort (alectinib-refractory subgroup [n = 47], 23.0 mo) and 22.1 mo in the TKI-naive cohort. Confirmed ORR was 34% (95% CI: 21–49) by IRC with 16 partial responses (PR) in the alectinib-refractory cohort and 32% (21–44; 22 PR) in the total refractory cohort. In the TKI-naive cohort, IRC-assessed 24-mo PFS was 73% (90% CI: 55–85); median PFS was not mature. Additional efficacy analyses are reported in Table. TEAEs were reported in all 104 pts (most common: increased CPK, 79%; hypertension, 48%; diarrhea, 47%). Grade ≥3 TEAEs were reported in 68% and 91% of pts in the TKI-refractory and -naive cohorts, respectively; most commonly (TKI-refractory/naive) elevated CPK, 24%/50%; elevated lipase, 15%/19%; hypertension, 11%/34%. Pneumonitis was mandated to be reported as an SAE regardless of severity and was the only SAE reported in > 5% of pts (refractory, n = 5 [7%; early onset, 1]; naive, n = 4 [13%; early onset, 0]). TEAEs led to dose interruption/reduction/discontinuation in 63%/31%/7% of pts in the TKI-refractory cohort and 94%/69%/0% in the TKI-naive cohort. Conclusions: Final efficacy and safety results in pts with TKI-refractory and -naive NSCLC were consistent with previous J-ALTA analyses. No new safety signals were observed in either cohort. Brigatinib demonstrated a favorable benefit-risk profile and is an important option for Japanese pts with ALK+ NSCLC regardless of TKI treatment history. Clinical trial information: NCT03410108.

^aWith/without prior crizotinib; ^b90% CI; ^cConfirmed responders. NR, not reached.