Efficacy and Safety of Ceritinib (450 mg/d or 600 mg/d) With Food Versus 750-mg/d Fasted in Patients With ALK Receptor Tyrosine Kinase (ALK)–Positive NSCLC: Primary Efficacy Results From the ASCEND-8 Study

Abstract Introduction In an earlier report of ASCEND-8 study (open-label, phase 1, 3-arm study, treatment-naive patients and pre-treated, advanced/metastatic NSCLC), it was shown that ceritinib 450 mg with food had comparable exposure and better gastrointestinal tolerability than 750-mg fasted. Methods Here, we report efficacy and updated safety data from primary efficacy analysis of ASCEND-8 study. Key secondary endpoints were overall response rate (ORR) and duration of response (DOR), assessed by blinded independent review committee (BIRC) using RECIST 1.1. Results In total, 306 patients were randomized to ceritinib 450-mg fed (n=108) or 600-mg fed (n=87) or 750-mg fasted (n=111), of which 304 patients were included in safety analysis and 198 treatment-naive patients ( ALK- positive by IHC) were included in the efficacy analysis (450 mg-fed [n=73], 600-mg fed [n=51], and 750-mg fasted [n=74]). The BIRC-assessed ORR 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), respectively; and the median DOR (months) by BIRC was not estimable (NE; 95% CI: 11.2–NE), 20.7 (95% CI: 15.8–NE), and 15.4 (95% CI: 8.3–NE), respectively. Based on the safety analysis (n=304), 450-mg fed arm showed the highest median relative dose intensity (100% vs 78.5% vs 83.7%), lowest proportion of patients with dose reductions (24.1% vs 65.1% vs 60.9%), and lowest proportion of patients with gastrointestinal toxicities (75.9% vs 82.6% vs 91.8%). Conclusion Ceritinib at a dose of 450 mg with food compared to 750-mg fasted showed consistent efficacy and less gastrointestinal toxicity.