ASCEND-8: safety data of ceritinib with or without food in NSCLC

Published: 26 Oct 2018

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Prof Byoung Chul Cho - Yonsei Cancer Center, Seoul, Republic of Korea

Prof Byoung Chul Cho speaks with ecancer at ESMO 2018 in Munich about results of the ASCEND-8 study which investigated the primary efficacy and updated safety of ceritinib (450 mg or 600 mg) with food vs 750 mg fasted in ALK positive metastatic NSCLC.

Prof Cho explains that ASCEND-8 was designed to look at the drawback of using ceritinib to treat NSCLC as, although it shows excellent progression-free survival, it does cause Gi toxicity.

He goes on to say that the study demonstrated that 450mg of ceritinib with meal and 750mg fasted had a similar pharmacokinetic profile.

ecancer's filming has been kindly supported by MSD through the ecancer Global Foundation. ecancer is editorially independent and there is no influence over content.

The ACEND-8 study is a global phase I study comparing 450mg with a meal, 600mg with a meal and 750mg fasted in advanced stage, treatment naïve, ALK positive lung cancer.

What led to the foundation of this study, what’s the background?

For ALK positive advanced stage non-small cell lung cancer ceritinib showed excellent objective response rates and progression free survival in our patients. The only problem of this drug is GI toxicity such as diarrhoea, nausea, vomiting. So in about 80% of patients patients experienced grade 1, sometimes grade 3, GI toxicity. So solving this GI toxicity from ceritinib was the question in our routine practice.

How many patients were recruited to each group?

In the ASCEND-8 study we enrolled about 80 patients in each treatment arm.

How were the results in let’s start off with the treatments with meal?

The study is composed of two parts: part 1 is a PK part and part 2 is an efficacy part. In part 1 we demonstrated the pharmacokinetic profile is similar between 450mg with a meal and 750mg fasted. In part 2 we demonstrated efficacy, including response rate, median progression free survival, duration of response, was similar between 450mg and 750mg. 750mg fasted has been the standard dosing for ceritinib before the emergence of the ASCEND-8 data.

What about the 600mg data?

The 600mg data, based on the PK profile, patients receiving 600mg had a 25% higher pharmacokinetic profile than 750mg or 450mg qd dose so we removed the 600mg qd with meal dose during the study based on the pharmacokinetic profile.

What does the timeline look like for further data to come from this study?

We completed enrolment and during this year at ESMO I presented the final efficacy data of the ASCEND-8 study demonstrating similar efficacy of 450mg with a meal with 750mg fasted with a much lower GI toxicity profile with 450mg. We need to have more data with further follow up regarding median progression free survival and median duration of response in the 450mg with a meal treatment arm.

Shall we expect those over the next year or is it a longer timescale?

The dose data will be available maybe by next year with longer term follow up.