Primary efficacy and updated safety of ceritinib (450 mg or 600 mg) with food vs 750 mg fasted in ALK+ metastatic NSCLC (ASCEND-8)

Abstract

Background: Previous PK analysis results from ASCEND‐8 study (NCT02299505) showed that ceritinib 450 mg with food had comparable exposure and more favorable GI safety profile than ceritinib 750 mg fasted in patients (pts) with ALK+ NSCLC. Methods: In this open‐label, phase 1, 3‐arm study, pts with treatment‐naïve or pretreated ALK+ advanced/metastatic NSCLC were randomized 1:1:1 to ceritinib 450 or 600 mg with food and 750 mg fasted, stratified by prior treatment and presence/absence of brain metastasis at screening. Key secondary endpoints were overall response rate (ORR) and duration of response, per BIRC using RECIST 1.1. Efficacy analysis was based on all treatment‐naïve pts with ALK+defined by IHC. Safety analysis was based on all pts who received ≥1 dose of study drug. Primary efficacy analysis and updated safety results are presented here (data cut off: 27 March 2018). Results: A total of 306 pts were randomized to ceritinib 450 mg fed (n=108) or 600 mg fed (n=87) or 750 mg fasted (n=111). Of those, 198 were treatment‐naïve with ALK+ by IHC and were assessed for efficacy (450 mg fed [n=73], 600 mg fed [n=51], and 750 mg fasted [n=74]). Median duration of study follow up was 19.6 months (mo) (range, 4.2‐35.3) in all randomized pts and 14.3 mo (range, 4.2‐30.2) in treatment‐ naïve pts who were ALK+ by IHC. ORR by BIRC was 78.1% (95% CI, 66.9‐86.9), 72.5% (95% CI, 58‐3‐84‐1), and 75.7% (95% CI, 64.3‐84.9) in the 450 mg fed, 600 mg fed and 750 mg fasted arms, respectively. Other efficacy results are shown in the table. The 450 mg fed arm, when compared to 600 mg fed and 750 mg fasted arms, showed highest median relative dose intensity (100% vs 78.5% vs 83.7%), lowest proportion of pts with dose reductions (24.1% vs 65.1% vs 60.9%), all grade GI toxicities (75.9% vs 82.6% vs 91.8%) and grade 3/4 GI toxicities (2.8% vs 8.1% vs 13.6%). Conclusions: Ceritinib 450 mg fed dose compared to 750 mg fasted showed consistent anti‐tumor efficacy and improved GI tolerability in pts with ALK+advanced NSCLC.