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

Abstract Background We report an analysis of Asian vs non-Asian pts with CRZ-refractory, ALK+ NSCLC from ALTA (NCT02094573). Methods 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. Results 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 (57–91b)29.5 (14.5–NRb) 67 (54–76b) 53 (41–64b)34.1 (22.6–NRb) 76 (65–84b) 62 (50–71b)– – –– – –– – –– – –DoR, duration of response; NR, not reached; ORR, objective response rate; OS, overall survival; PFS, progression-free survival. a97.5% CI (primary endpoint); b95% CI; cKaplan-Meier estimate. Conclusions BRG showed comparable efficacy and acceptable safety in Asians and non-Asians in CRZ-refractory ALK+ NSCLC, with nonsignificant, numerically improved PFS at the 180-mg (with lead-in) dose. Clinical trial identification NCT02094573. Editorial acknowledgement Peloton Advantage, LLC, an OPEN Health Company, funded by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Legal entity responsible for the study ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Funding ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Disclosure D.H. Lee: Honoraria (self): AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, ChongKunDang, CJ Healthcare, Eli Lilly, Genexine, Janssen, Merck, MSD, Mundipharma, Novartis, Ono, Pfizer, Roche, Samyang Biopharm, ST Cube, Takeda. D. Kim: Research grant / Funding (institution): Alpha Biopharma, Astrazeneca/MedImmune, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan. D.R. Camidge: Honoraria (self): AstraZeneca, Takeda, Genoptix, G1 Therapeutics [DSMB], Mersana Therapeutics, Roche, Ignyta, Daiichi Sankyo [ILD adjudication committee], Hansoh SRC, Bio-Thera DSMB, Lycera, Revolution Med; Research grant / Funding (self): Takeda. C.J. Langer: Honoraria (self): Bristol-Myers Squibb, Eli Lilly, Roche/Genentech; Advisory / Consultancy: Abbott, ARIAD, AstraZeneca, Bayer/Onyx, Bristol-Myers Squibb, Cancer Support Community, Celgene, Clarient, Clovis Oncology, Eli Lilly, Merck, Roche/Genentech, Takeda; Research grant / Funding (self): Advantagene, ARIAD, Celgene, Clovis Oncology, GlaxoSmithKline, Inovio, Merck, Roche/Genentech, Stemcentrx; Advisory / Consultancy: Amgen, Lilly, Peregrine Pharmaceuticals, Synta. R.M. Huber: Honoraria (self): ARIAD, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Roche; Advisory / Consultancy: Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Clovis Oncology, Eli Lilly, Novartis, Roche; Research grant / Funding (self): Pierre Fabre. M. Tiseo: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Otsuka, Pfizer, Pierre Fabre, Roche. H.L. West: Advisory / Consultancy: AbbVie, ARIAD, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Merck, PharmaMar, Roche/Genentech, Spectrum, Takeda; Speaker Bureau / Expert testimony: ARIAD, Bristol-Myers Squibb, Roche/Genentech. H.J.M. Groen: Advisory / Consultancy: AbbVie, BMS, Eli Lilly, MSD, Novartis, Pfizer, Roche/Genentech; Research grant / Funding (self): Eli Lilly, Roche. K.L. Reckamp: Advisory / Consultancy: Amgen, ARIAD, Astellas, Takeda, Tesaro; Research grant / Funding (self): Adaptimmune, ARIAD, BMS, Boehringer Ingelheim, AbbVie, Novartis, Pfizer, Roche/Genentech, Xcovery. M.J. Hochmair: Honoraria (self): AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, Roche, Takeda; Advisory / Consultancy: Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, Roche, Takeda. N.B. Leighl: Travel / Accommodation / Expenses: AstraZeneca, BMS, MSD, Pfizer. K.H. Hansen: Honoraria (self): AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Roche; Advisory / Consultancy: AstraZeneca, BMS, Boehringer Ingelheim, Lilly, MSD, Roche; Travel / Accommodation / Expenses: BMS, Boehringer Ingelheim, MSD, Pfizer, Roche. S.N. Gettinger: Advisory / Consultancy: Alexion Pharmaceuticals, ARIAD, Bristol-Myers Squibb, Pfizer; Research grant / Funding (self): ARIAD, Bristol-Myers Squibb, Incyte, Pfizer, Roche/Genentech. L. Paz-Ares: Honoraria (self), Spouse / Financial dependant: Eli Lilly, MSD, BMS, Roche, PharmaMar, Merck, AstraZeneca, Novartis, Boehringer Ingelheim, Celgene, Servier, Sysmex, Amgen, Incyte, Pfizer, Ipsen, Adacap, Sanofi, Bayer, Blueprint; Officer / Board of Directors: Genomica; Research grant / Funding (institution): MSD, BMS, AstraZeneca, Pfizer. E.S. Kim: Advisory / Consultancy: AstraZeneca, Celgene, Eli Lilly; Honoraria (self): Eli Lilly, AstraZeneca, Celgene. E.F. Smit: Advisory / Consultancy: Eli Lilly; Research grant / Funding (self): AstraZeneca, Bayer, Boehringer Ingelheim, Roche/Genentech. Q. Ni: Full / Part-time employment: Takeda. P. Zhang: Full / Part-time employment: Takeda. M. Ahn: Honoraria (self): AstraZeneca, Boehringer Ingelheim, Lilly, MSD; Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Lilly, MSD. All other authors have declared no conflicts of interest.