Journal article

A multi-arm phase I dose escalating study of an oral NOTCH inhibitor BMS-986115 in patients with advanced solid tumours

Kyaw L Aung, Anthony B El-Khoueiry, Karen Gelmon, Ben Tran, Gaurav Bajaj, Bing He, Tian Chen, Lili Zhu, Sharath Poojary, Shashwati Basak, Zhenhao Qi, Anna Spreafico, Bruce S Fischer, Jayesh Desai



Background Inhibiting Notch is a promising anti-cancer strategy as it plays a critical role in cancer stem cells maintenance and tumour angiogenesis. BMS-986115 is an orally active, selective inhibitor of gamma-secretase mediated Notch signalling. Method Two dose escalation schedules (Arm-A continuous daily schedule and Arm-B intermittent 2 times weekly schedule) of BMS-986115 were evaluated in advanced solid tumour patients. The primary objective was to establish the safety, tolerability and Maximum Tolerated Dose (MTD) of BMS-986115. Results Thirty six patients (24 in Arm A and 12 in Arm B) were treated. The most frequent treatment related adverse advents were diarrhoea (72%), hypophosphat..

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