1295PEFFICACY AND SAFETY OF CERITINIB IN PATIENTS (PTS) WITH ADVANCED ANAPLASTIC LYMPHOMA KINASE (ALK)-REARRANGED (ALK+) NON-SMALL CELL LUNG CANCER (NSCLC): AN UPDATE OF ASCEND-1

ABSTRACT Aim: ALK+ tumors are sensitive to ALK tyrosine kinase inhibitors such as crizotinib (CRZ) but resistance invariably develops. Ceritinib (LDK378), a novel ALK inhibitor (ALKi), is more potent than CRZ in vitro and is effective in CRZ-resistant disease. Updated data from ASCEND-1 (NCT01283516) are presented, focused on pts receiving ceritinib at the recommended 750 mg/day dose and with longer follow-up. Methods: Investigator assessment of efficacy is presented for pts with ALK+ NSCLC receiving ≥1 dose of ceritinib at 750 mg/day prior to 31 Oct 2013. Results with additional follow-up will be presented. Results: 246 pts with ALK+ NSCLC had 7 months median duration of follow up. Of these, 230 (93%) had received prior antineoplastic therapy, 166 (67%) with ≥2 prior regimens.163 (66%) had received prior ALKi, all of whom had received CRZ; of these, 91% had progressive disease during prior ALKi therapy and 78% had received ALKi as last prior therapy. Efficacy is shown below. Endpoint All NSCLC n = 246 ALKi-pretreated n = 163 ALKi-naive n = 83 ORR, n (%) [95% CI] 144 (58.5) [52.1, 64.8] 89 (54.6) [46.6, 62.4] 55 (66.3) [55.1, 76.3] DOR, median (months) [95% CI] 9.7 [7.0, 11.4] 7.4 [5.4, 10.1] NEa [9.6, NE] Time to first response, median (weeks) [min, max] 6.1 wks [3.0, 24.1] 6.1 wks [4.6, 24.1] 6.1 wks [3.0, 24.1] PFS, median (months) [95% CI] 8.2 [6.7, 10.1] 6.9 [5.4, 8.4] NEb [8.3, NE] aDOR rate at 12 mos 65.2% [95% CI: 46.4, 78.8] bPFS rate at 12 mos 61.3% [95% CI: 47.7, 72.3] NE = Not estimable. Discontinuation of treatment due to adverse event (AE) occurred in 24 (10%) pts with NSCLC; 17 (10%) ALKi-pretreated pts and 7 (8%) ALKi-naive pts. Among all 255 pts receiving ceritinib 750 mg/day, 99 (39%) and 51 (20%) required 1 and >1 ceritinib dose reduction, respectively. The most common AEs of any grade (>50%) were diarrhea (86%), nausea (80%), vomiting (60%), abdominal pain (54%), fatigue (52%). Most common lab abnormalities of any grade (>50%) were decreased hemoglobin (84%), increased ALT (80%), increased AST (75%), increased creatinine (58%). Most common Grade 3/4 lab abnormalities (>10%) were increased ALT (27%), increased AST (13%), increased glucose (13%). One treatment-related death (interstitial lung disease) was reported. Conclusions: Ceritinib 750 mg/day shows potent anti-tumor activity in ALK+ NSCLC pts regardless of prior ALKi treatment status. Discontinuation due to toxicity was uncommon. Disclosure: E. Felip: Advisory board: BI, Novartis, Roche, BMS, Lilly; D. Kim: Consultation for Novartis, Pfizer, Lilly; Honorarium from Pfizer, Lilly; R. Mehra: Spouse is an employee of GSK, consulting to Bristol-Myers Squibb and Novartis; L.Q. Chow: Employee: University of Washington; Research grant and research support, consultant, travel expenses and advisory board: Novartis; D.R. Camidge: Advisory boards/consultancy/honoraria for Servier, Eli Lilly, Genentech/Roche, Astex, Ariad, ImmunoGen, Clarient, Excelixis, indiPharm, Astellas, Boehringer Ingelheim, Chugai, Clovis, Array Biopharma, AstraZeneca, Aveo, Novartis, Synta, Pfizer; J.F. Vansteenkiste: Speaker for Novartis; S. Sharma: Research grant, Consultant: Novartis. Stock: Salarius Pharma, Beta Cat Pharma, ConverGene. Leadership: Board member, TheraTarget and Member, VLB Therapeutics IDMC; B. Solomon: Honoraria/Ad board: Novartis, Pfizer, Clovis, Clovis oncology, AZ, Roche; J. Wolf: Employee of University Hospital of Cologne. Ad boards, speakers bureau and research funding: AZ, Novartis, Roche, Pfizer, BI, BMS, Clovis. Research support: Novartis, Roche, BI; M. Thomas: Honoraria: Lilly, BMS, Roche. Consultant: Lilly, BMS, Roche, Novartis ; M. Schuler: Consultant: AZ, BI, Novartis, Pfizer. Research grants to institution: BI, Novartis. Honoraries for CME lectures: BI, Celgine, GSK, Lilly, Novartis, Pfizer; G. Lui: Consultant: AZ, Pfizer, Novartis; M. Geraldes: Margarida Geraldes is an employee of Novartis and is a stock owner; A.L. Boral: Antony L Boral is an employee of Novartis; A. Yovine: Alejandro Yovine is an employee of Novartis and is a stock owner; A.T. Shaw: Advisory board: Novartis, Pfizer, Ariad, Chugai, Genentech. All other authors have declared no conflicts of interest.