Preliminary activity in adrenocortical tumour (ACC) in phase I dose escalation study of intermittent oral dosing of OSI-906, a small molecule insulin like growth factor-1 receptor (IGF-1R) tyrosine kinase inhibitor in patients with advanced solid tumours


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S Alam1, C Carden1, M Langham2, S Frentzas1, S Dolly1, S Sandhu1, R Kristeleit1, T Yap1, I Casamayor1, T Matthews1, AW Stephens3, S Poondru3, E Kim2, SB Kaye.1

1Institute of Cancer Research, Royal Marsden Hospital, London, UK, 2MD Anderson Cancer Centre, Texas, USA, 3OSI Pharmaceuticals, Colorado, USA

Abstract

Background

Insulin-like growth factor-I receptor (IGF-IR) plays an important role in tumour cell growth and survival. IGF-1R blockade increases apoptosis, chemosensitivity and reduces tumour growth in many preclinical models. OSI-906 is an oral IGF-1R, tyrosine kinase inhibitor.

Method

Patients (pt) with advanced solid tumours were enrolled to determine safety, tolerability, maximum tolerated dose, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumour activity.

Results

33 pt have been treated (19M: 14F, median age 62 yrs) at 10, 20, 40, 80, 150, 300 and 450mg on days (d) 1-3 q14 d, and at 450mg d 1-5 q14d. No dose-limiting toxicities have been observed to date. Drug-related toxicities include grade 2 hyperglycaemia and grade 1 fatigue, nausea, rash, diarrhoea, tachycardia, proteinuria, pruritis and peripheral oedema. Linear PK was observed, with median terminal t1/2