I would like to talk about preliminary results of a phase I study of ASP8273, a reversible EGFR mutant selective new EGFR TKI. EGFR activated mutations are found in approximately 30% of East Asian non-small cell lung cancer patients so EGFR TKIs, gefitinib, erlotinib and afatinib, are standard therapy for non-small cell lung cancer patients with EGFR activating mutations. However, the clinical activity of EGFR TKIs is limited by the development of acquired resistance which is commonly caused by T790M mutation.

What did the study entail?

ASP8273 is an orally available third generation EGFR TKI that inhibits kinase activity of EGFR activated mutation as well as T790M resistance mutation. We’ve conducted the phase I studies of ASP8273 in Japan since January 2014. A total of 31 patients were enrolled in the study. ASP8273 was administered once daily. We escalated the dose of ASP8273 from 25mg to 600mg.

What adverse effects did you see?

Common adverse events were mild GI toxicities such as diarrhoea, nausea and vomiting. Diarrhoea was observed in half of the patients and nausea and vomiting were observed in a third of the patients.

What was the response rate?

24 patients were evaluated for tumour response based on RECIST criteria. Tumour responses were observed at the doses of 100mg or more. Among the 9 patients with T790M mutation positive patients tumour shrinkage was observed in all 9 patients. Tumour response rate was 78% with 7 partial responses and 2 stable disease.

What are the potential clinical implications?

The number of patients is too small. I think ASP8273 would be expected to have clinical benefit, especially for patients with T790M mutation positive patients.

What are the next steps?

The next step is a phase II study. The total number of patients is 124.