An extended phase Ib study of epertinib, an orally active reversible dual EGFR/HER2 tyrosine kinase inhibitor, in patients with solid tumours

Dose-escalation of epertinib (S-222611), a new potent oral EGFR/HER2 inhibitor, has established a recommended daily dose of 800 mg in patients with solid tumours. In this study, we have recruited a larger number of patients to assess further the safety, tolerability, pharmacokinetics (PKs) and antitumour activity.

Patients with solid tumours expressing EGFR or HER2 received a single dose of epertinib at 800 mg on Day 1 to assess PK over 7 days, followed by continuous once-daily dosing from Day 8.

We treated 76 patients with breast (n = 27), upper gastrointestinal (GI; n = 30), head and neck (n = 12) or renal cancers (n = 7). Epertinib was well-tolerated with mostly grade I and II adverse events (AEs). The most frequent AE was diarrhoea, which was generally manageable with loperamide. The objective response rate (ORR) in patients with heavily pretreated breast and upper GI cancers was 16.0% (4 PRs) and 8.3% (1CR, 1PR), respectively. All six responding patients had HER2-positive tumours; the ORR for HER2-positive breast and upper GI cancer populations was 19.0% and 20.0%. Partial response in the brain disease of one breast cancer patient lasted 7.5 months.

Once-daily dosing of epertinib at 800 mg was well-tolerated and demonstrated promising antitumour activity in patients with heavily pretreated HER2-positive breast and upper GI cancer, including those with brain metastases.

2009-017817-31.

European journal of cancer (Oxford, England : 1990). 2018 Sep 06 [Epub ahead of print]

H-T Arkenau, A Italiano, G Mak, M Toulmonde, R D Baird, J Garcia-Corbacho, R Plummer, M Flynn, M Forster, R H Wilson, D Tosi, A Adenis, K Donaldson, J Posner, I Kawabata, A Arimura, S Deva, J Spicer

Sarah Cannon Research Institute UK, London, United Kingdom; UCL Cancer Institute and NIHR UCLH Clinical Research Facility, University College London Hospitals, London, United Kingdom., Early Phase Trials and Sarcoma Units, Institut Bergonie, Bordeaux, France., Sarah Cannon Research Institute UK, London, United Kingdom., Breast Cancer Research and Early Phase Trials Teams, Cancer Research UK Cambridge Centre, Cambridge, United Kingdom., Northern Institute for Cancer Research, Newcastle University, Newcastle Upon Tyne and Sir Bobby Robson Cancer Trials Research Centre, Freeman Hospital, Newcastle upon Tyne, United Kingdom., UCL Cancer Institute and NIHR UCLH Clinical Research Facility, University College London Hospitals, London, United Kingdom., Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom and Northern Ireland Cancer Center, Belfast City Hospital, Belfast, United Kingdom., Early Clinical Trial Unit, Institut Régional Du Cancer de Montpellier (ICM), Montpellier, France., Department of Medical Oncology, Centre Oscar Lambret, Lille, France., Shionogi & Co., Ltd., Osaka, Japan., School of Cancer and Pharmaceutical Sciences, King's College London, Guy's Hospital, London, United Kingdom., School of Cancer and Pharmaceutical Sciences, King's College London, Guy's Hospital, London, United Kingdom. Electronic address: .