Integrated efficacy and safety of brigatinib in patients with ALK TKI-naive advanced ALK+ NSCLC in the ALTA-1L and J-ALTA studies.

9078 Background: Brigatinib demonstrated efficacy and manageable safety in patients (pts) with anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI)-naive ALK+ non-small cell lung cancer (NSCLC) in phase 3 (ALTA-1L) and phase 2 (J-ALTA) trials. We present results of integrated efficacy and safety analyses of ALTA-1L and J-ALTA. Methods: ALTA-1L (NCT02737501) and J-ALTA (NCT03410108; conducted in Japan) were open-label, multicenter studies in pts with advanced or metastatic ALK+ NSCLC. Pts in ALTA-1L and in part 3 of J-ALTA were ALK TKI-naive. Stable or asymptomatic brain metastases were allowed in both studies. Pts received brigatinib 180 mg qd (7-day lead-in at 90 mg). Primary endpoints were blinded independent review committee (IRC)-assessed progression-free survival (PFS) in ALTA-1L and IRC-assessed 12-month PFS in the J-ALTA ALK TKI-naive cohort (both per RECIST v 1.1). Secondary endpoints included IRC-assessed objective response rate (ORR), duration of response, intracranial ORR, intracranial PFS, overall survival, and safety. Pooled efficacy and safety data from both studies are presented. Results: The pooled analysis population included 169 pts (ALTA-1L, N = 137; J-ALTA ALK TKI-naive cohort, N = 32). Median follow-up overall was 35.8 months (last pt last contact: ALTA-1L, January 2021; J-ALTA, July 2021). Most (66%) pts were aged < 65 years, 24% had baseline brain metastases, 95% had stage IV disease at study entry, and 21% had received prior chemotherapy for locally advanced or metastatic disease. With brigatinib treatment, median PFS by IRC was 29.3 months (95% CI, 23.9‒44.7). The confirmed ORR was 79% (95% CI, 72‒85%), with 36 complete responses and 97 partial responses. Median duration of response was 38.1 months (95% CI, 22.9‒not reached). Median overall survival was not reached; the 3-year survival rate was 74% (95% CI: 66‒80%; 84 pts at risk). Intracranial ORR and intracranial PFS will be presented. Grade 3/4 treatment-emergent adverse events were reported in 74% of pts; the most common were increased blood creatine phosphokinase (31%), hypertension (18%), and increased lipase (16%). Any grade interstitial lung disease/pneumonitis was reported in 12 (7%) of pts. Adverse events led to treatment discontinuation in 11% of pts. Conclusions: Brigatinib treatment demonstrated clinically meaningful systemic and intracranial efficacy in this integrated analysis of pts with ALK TKI-naive advanced or metastatic ALK+ NSCLC in the ALTA-1L or J-ALTA trials. Safety results were consistent with the known profile for brigatinib, with no new safety findings. Clinical trial information: NCT02737501 ; NCT03410108 .