Phase I/IIa, open-label, multicentre study to evaluate the optimal dosing and safety of ODM-203 in patients with advanced or metastatic solid tumours.

Background Genetic alterations in fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR) signalling are observed in various tumours. We report a first-in-human phase I/IIa trial evaluating tolerability, pharmacokinetics and preliminary antitumour activity of ODM-203, a novel FGFR and VEGFR inhibitor. Methods Open-label, non-randomised, multicentre, phase I/IIa dose escalation and expansion study in patients with advanced or metastatic solid tumours. Results Overall, 84 patients received treatment; optimal tablet dose was found to be 400 mg/day with food. All patients experienced at least one adverse event; the majority (89.2%) were grade 1 or 2% and 70.4% were considered treatment related. The most commonly reported events were bilirubin increase-related events (75%) and diarrhoea (50%). Overall response rate was 9.2% and median progression-free survival was 16.1 and 12.4 weeks for patients with aberrant or non-aberrant FGFR tumours. Median time on treatment was 10.1 weeks for all patients and 14.5 weeks for patients who received 400 mg tablets. Conclusion This study suggests ODM-203 400 mg/day results in sufficient plasma concentrations and acceptable tolerability in most patients. Preliminary signs of therapeutic activity of ODM-203 in patients with solid tumours was observed. Trial registration number NCT02264418.