OA 05.07 Efficacy and Updated Safety of Ceritinib (450 Mg or 600 Mg) with Low-Fat Meal vs 750 Mg Fasted in ALK+ Metastatic NSCLC

Ceritinib plus Nivolumab in Patients with Advanced ALK-Rearranged Non–Small Cell Lung Cancer: Results of an Open-Label, Multicenter, Phase 1B Study

“…Other frequent grade 3 or 4 AEs were increased ALT level, increased GGT level, increased amylase level, and increased lipase level; however, these AEs were not increased compared with those known for either agent. The incidence of diarrhea and vomiting in the 450-mg fed cohort was higher than that reported with ceritinib, 450 mg fed, in the ASCEND-8 study, 11 perhaps because of the fact that nivolumab is also known to be associated with these AEs. 16,17 However, no increased frequency of colitis was observed and these AEs were managed by dose interruption, dose reduction, or supportive concomitant medication.…”

“…26 This finding is consistent with the results of the ASCEND-8 study, which demonstrated that ceritinib in a dose of 450 mg with food had comparable exposure and efficacy, with improved gastrointestinal safety than with ceritinib, 750 mg, in fasted patients with ALK-rearranged NSCLC. 10,11 The trough concentration of nivolumab reached steady state by cycle 8 and remained stable afterward. Accumulation of the trough concentration from the first dose to steady state was 3.7-fold, which is consistent with the published values.…”

“…[5][6][7][8][9] Recent data from a phase 1 study of ceritinib (ASCEND-8 [NCT02299505]) showed that the frequency and severity of gastrointestinal toxicities were lower with a starting dose of 450 mg/d administered with food with a dose of 750 mg/d when patients fasted, with fewer patients requiring dose reduction or interruption, resulting in a higher median relative dose intensity and comparable efficacy. 10,11 On the basis of the ASCEND-8 data, the 450-mg dose of ceritinib with food was recently approved as the recommended dose in the United States 12 and Europe. 13 Nivolumab (proprietary name Opdivo, Bristol-Myers Squibb, NY) is a PD-1 immune checkpoint inhibitor approved by the U.S. Food and Drug Administration for metastatic NSCLC that has progressed during or after platinum-based chemotherapy 14 and approved in Europe for locally advanced or metastatic NSCLC after prior chemotherapy.…”

Phase II study of ceritinib in alectinib‐pretreated patients with anaplastic lymphoma kinase‐rearranged metastatic non‐small‐cell lung cancer in Japan: ASCEND‐9

“…Overall, gastrointestinal AE (diarrhea, nausea, and vomiting) were the most frequently reported all‐causality drug‐related AE. Recent data from a phase I study of ceritinib (ASCEND‐8; NCT02299505) show that the frequency and severity of gastrointestinal toxicities was lower with a starting dose of 450 mg/day under fed condition compared to that with the currently approved recommended dose of 750 mg/day under fasted condition, with fewer patients requiring dose reduction or interruption, resulting in the higher median relative dose intensity and comparable efficacy . Thus, ceritinib treatment with this new starting dose of 450 mg/day under fed condition is expected to improve the relative dose intensity on account of a better gastrointestinal safety profile and more favorable benefit/risk profile.…”

Phase 3 study of ceritinib vs chemotherapy in ALK-rearranged NSCLC patients previously treated with chemotherapy and crizotinib (ASCEND-5): Japanese subset

“…Recently, it was demonstrated that ceritinib 450 mg administered with food had comparable exposure to ceritinib 750 mg fasted in patients with ALK + NSCLC with a more favorable safety profile (less frequent/severe GI toxicity and dose modifications resulting higher treatment exposure) in both treatment naive and pretreated patients ( 18 ) and promising emerging efficacy in treatment-naive patients with ALK + metastatic NSCLC ( 19 ). The result suggests that lower dose of ceritinib with food may be a preferred regimen with improved GI tolerability and high antitumor activity.…”