8003^ Background: ALK+ NSCLC is sensitive to crizotinib (CRZ) but patients (pts) invariably progress. Ceritinib (LDK378) is a novel ALK inhibitor (ALKi) more potent than CRZ in enzymatic and cell-based assays and CRZ-resistant animal models. Prior results from this Phase I study (ASCEND-1) established a MTD of 750 mg/d. Methods: Adult pts with advanced ALK+ cancers received oral ceritinib q.d. After MTD determination, pts were enrolled to expansion groups: ALKi pretreated (PT) NSCLC; ALKi naive NSCLC; non-NSCLC diseases. Results are reported for all NSCLC pts receiving ceritinib at the recommended dose (750 mg/d). Results: 255 pts from 11 countries were treated at 750 mg/d. 246 pts had ALK+ NSCLC, with 4.5 months’ median follow-up; of these, 67% had received ≥2 anticancer therapies; ORR was ≥60% in each subgroup of pts with 0, 1, 2, and 3 prior anticancer regimens. 83 pts were ALKi naïve. All 163 ALKi PT pts had received CRZ – 78% as their last prior therapy – and 92% had progressive disease on prior ALKi. Investigator efficacy assessments are presented for 180 NSCLC pts who received first dose of ceritinib ≥18 wks prior to cut-off (2 Aug 2013). Of all 255 pts, the most common AEs were diarrhea (84%), nausea (77%), vomiting (57%), fatigue (36%), and ALT increased (36%). The most common Grade 3/4 AEs were ALT increased (21%), and AST increased (8%). Ceritinib treatment is ongoing for 58% of pts. During the dosing period dose reductions occurred in 133 pts (52.2%), all due to an AE. Only 24 (9.4%) pts discontinued ceritinib due to an AE. Conclusions: Ceritinib 750 mg/d has rapid, durable and high antitumor activity in ALK+ NSCLC pts, regardless of prior treatment with ALKi, providing effective treatment in this pt population. Clinical trial information: NCT01283516. Endpoint ALKi PT N=121 ALK naive N=59 All N=180 ORR, n (%) [95% CI] 67 (55.4%) [46.1, 64.4] 41 (69.5%) [56.1, 80.8] 108 (60.0%) [52.4, 67.2] DOR (Median [95% CI]) 7.4 mos [5.4, 10.1] NEa [5.6, NE] 9.7 mos [6.9, 11.4] Time to first response (Median [min, max]) 6.1 wks [4.6, 24.1] 6.1 wks [3.0, 24.1] 6.1 wks [3.0, 24.1] PFS (Median [95% CI]) 6.9 mos [5.4, 8.7] NEb [6.7, NE] 7.0 mos [6.2, 10.1] Abbreviation: NE, not estimable. a DOR rate at 12 mos: 71.1% (95% CI: 49.8, 84.6). b PFS rate at 12 mos: 58.1% (95% CI: 41.6, 71.5).