1478OResults of the ASCEND-7 phase II study evaluating ALK inhibitor (ALKi) ceritinib in patients (pts) with ALK+ non-small cell lung cancer (NSCLC) metastatic to the brain

Abstract Background Ceritinib is approved for the treatment of pts with metastatic ALK+ NSCLC. In previous studies (ASCEND-1 to 5), ceritinib was highly active in ALK+ NSCLC pts with reported intracranial responses in pts with measurable baseline brain lesions. ASCEND-7 (NCT02336451) was designed to specifically study intracranial effects of ceritinib and we report here efficacy and safety in pts with ALK+ NSCLC metastatic to the brain (Arms 1-4). Methods Eligible pts had, WHO performance status 0-2, ALK + (FISH) NSCLC, with active brain metastases (BM) either newly diagnosed or progressive, and ≥1 extracranial measurable lesion using RECIST v1.1. Pts may have been pretreated with chemotherapy and/or crizotinib (ALK inhibitor [ALKi]). Pts were assigned to arms 1 to 4 depending on prior treatment (refer to below table). Primary endpoint was investigator assessed whole body overall response rate (CR or PR) and key secondary endpoint was investigator assessed disease control rate (CR or PR or SD). Intracranial responses and extracranial responses were assessed using modified RECIST 1.1 and RECIST 1.1, respectively. Results As of 6-Feb-2019, 138 pts were treated in Arms 1-4 (Arm 1: 42; Arm 2: 40; Arm 3: 12; Arm 4: 44), and all the pts discontinued the treatment. Median follow-up for whole body progression free survival was 5.49 months across Arm 1-4. Efficacy endpoints by investigator assessment are reported in the below Table. Most common AEs (>50% all grades in any of the Arms 1-4) regardless of causality were diarrhoea, nausea, ALT increased, vomiting, AST increased, decreased appetite. Majority of these AEs was grade 1/2. Table:1478O Overall efficacyArm 1 (prior brain radiotherapy and prior ALKi) N = 42Arm 2 (no prior brain radiotherapy and prior ALKi) N = 40Arm 3 (prior brain radiotherapy and no prior ALKi) N = 12Arm 4 (no prior brain radiotherapy and no prior ALKi) N = 44Whole body efficacy (RECIST v1.1) ORR, % [95% CI] DCR, % [95% CI] 35.7 [21.6, 52.0] 66.7 [50.5, 80.4] 30.0 [16.6, 46.5] 82.5 [67.2, 92.7] 50.0 [21.1, 78.9] 66.7 [34.9, 90.1] 59.1 [43.2, 73.7] 70.5 [54.8, 83.2]Whole body efficacy (RECIST v1.1) Median DOR, months [95% CI] Estimated 6-month event-free probability, % [95% CI]L‡ = 15 10. 8 [4.1, NE] 64.6 [34.7, 83.5]L‡ = 12 12.8 [3.7, 17.3] 74.1 [39.1, 90.9]L‡ = 6 NE [11.7, NE] 100 [100, 100]L‡ = 26 9.2 [7.3, 23.9] 72.7 [51.1, 86.0]Whole body efficacy (RECIST v1.1) Median PFS, months [95% CI] Estimated 6-month event-free probability, % [95% C