1543P - Brigatinib (BRG) in Asian vs non-Asian patients (pts) with crizotinib (CRZ)-refractory ALK+ NSCLC in the phase II ALTA trial

We report an analysis of Asian vs non-Asian pts with CRZ-refractory, ALK+ NSCLC from ALTA (NCT02094573). Pts were stratified by presence of baseline (BL) CNS metastases and best response to prior CRZ and randomized 1:1 to BRG 90mg qd (arm A) or 180mg qd with a 7-day lead-in at 90mg (arm B). Primary endpoint: Investigator-assessed confirmed ORR by RECIST v1.1. 222 pts were randomized; 69 Asian (A/B, n=39/30), 153 non-Asian (n=73/80); median age: Asian, 50/56 y; non-Asian, 51/57 y; 85/70% vs 64/66% had BL CNS metastases. As of Sep 2017, median follow-up was 18.4/22.5mo (A/B) in Asians vs 22.3/24.5mo in non-Asians. In Asians, median IRC-assessed PFS (mo) was 9.1 (95% CI 5.6–18.2) in A vs 15.6 (9.2–21.2) in B (HR 0.88 [95% CI 0.48–1.62]; P=0.6808); in non-Asians, PFS (A/B) was 9.9 (9.0–26.3) vs 17.9 (11.6–23.9; HR 0.72 [0.45–1.13]; P=0.1510) (Table). Of 7/2 (A/B) Asian pts with measurable BL CNS metastases, 3/1 had confirmed intracranial objective responses; in non-Asian pts with measurable BL CNS metastases, IRC-assessed iORR was 53/69% (n=19/16). In Asians (A vs B) with any BL CNS metastases, IRC-assessed median iPFS (mo) was 15.6 (5.6–18.4) vs 12.8 (7.3–21.1); in non-Asians, 12.8 (7.4–NR) vs 20.7 (11.1–NR). Most common any-grade TRAEs in Asians (≥20%): increased CPK and amylase; in non-Asians, nausea, diarrhea, and increased CPK. Most common grade ≥3 TRAEs (>3%) in Asians: increased CPK; in non-Asians, increased CPK and lipase, hypertension. Early-onset pulmonary AEs occurred in 3 (4%; 1 grade ≥3) Asian (Korean) and 11 (7%; 6 grade ≥3) non-Asian pts. Dose reductions due to AE: 7.7/30.0% in Asian pts; 7.1/28.8% in non-Asian pts; discontinuations due to AE: 7.7/16.7% in Asian pts; 10.0/20.0% in non-Asian pts.Table1543PTableInvestigator-AssessedIndependent Review Committee (IRC)–AssessedAsian (n=69)Non-Asian (n=153)Asian (n=69)Non-Asian (n=153)Arm A (n=39)Arm B (n=30)Arm A (n=73)Arm B (n=80)Arm A (n=39)Arm B (n=30)Arm A (n=73)Arm B (n=80)Confirmed ORR, %49 (30–67a)67 (45–84a)44 (31–58a)53 (40–65a)56 (40–72b)67 (47–83b)48 (36–60b)53 (41–64b)Median DoR in responders,c mo13.7 (5.6–19.4b)13.8 (10.2–14.8b)9.5 (7.4–NRb)16.6 (9.0–24.0b)16.4 (5.6–24.9b)13.9 (7.4–19.4b)24.6 (7.4–NRb)15.7 (12.6–30.2b)Median PFS,c mo Events, %9.2 (5.6–15.6b) 6915.6 (11.1–15.7b) 609.2 (5.7–11.1b) 6914.7 (10.8–24.0b) 589.1 (5.6–18.2b) 6715.6 (9.2–21.2b) 609.9 (9.0–26.3b) 5317.9 (11.6–23.9b) 45OSc Median, mo 1-y,c % 2-y,c %NR (18.2–NRb) 77 (60–88b) 56 (37–72b)NR (NR–NRb) 92 (73–98b) 79 (57–